Dolor Neuropatico.

Dolor Neuropatico

La presentación a través de los estados del dolor varía
Dolor neuropático Dolor iniciado o causado por una lesión primaria o disfunción en el sistema nervioso (sistema periférico o nervioso central )1 Dolor nociceptivo Dolor causado por lesión a tejidos blandos (musculoesqueléticos, cutáneos o viscerales)2 Dolor mixto Dolor con componentes neuropáticos y nociceptivos Ejemplos Periférico Neuralgia Posherpética Neuralgia del trigémino Neuropatía diabética periférica Neuropatía posquirúrgica central Dolor post accid vasc cerebral Descriptores frecuentes 2 Ardor Hormigueo Hipersensibilidad al tacto o frío Ejemplos Lumbalgia con radiculopatía Radiculopatía cervical Dolor por cáncer Síndrome del túnel carpal Ejemplos Dolor debido a inflamación Dolor en miembro después de una fractura Dolor articular por osteoartritis Dolor postoperatorio visceral This slide illustrates three broad categories of pain: neuropathic (pathologic), nociceptive (physiologic), and mixed pain states that encompass both nociceptive and neuropathic components, with examples of common causes of each type of pain. The key talking points on this slide are as follows: Neuropathic pain has been defined by the International Association for the Study of Pain as ‘initiated or caused by a primary lesion or dysfunction in the nervous system’.1 Depending on where the lesion or dysfunction occurs within the nervous system, neuropathic pain can be peripheral or central in origin. Causes of peripheral neuropathic pain include postherpetic neuralgia (PHN) and diabetic peripheral neuropathy (DPN). Due to the prevalence and characteristics of PHN and DPN, these states may be considered representative of peripheral neuropathic pain. Nociceptive pain is an appropriate physiologic response that occurs when specific peripheral sensory neurons (nociceptors) respond to noxious stimuli. Nociceptive pain has a protective role because it elicits reflex and behavioral responses that keep tissue damage to a minimum. Acute pain, such as that seen with tissue inflammation and chronic pain, such that accompanying osteoarthritis, are examples of nociceptive pain. Although there are no specific descriptors for each type of pain, neuropathic pain is frequently described as ‘burning or tingling’ in quality, while nociceptive pain is often described as ‘aching or throbbing’. There are cases in which an individual experiences pain sensations that are a blend of pain having a nociceptive and a neuropathic origin. For example, in carpal tunnel syndrome, it is common experience to have nociceptive pain, felt around the wrist, and neuropathic pain, felt in the distribution territory of the median nerve (fingers). References International Association for the Study of Pain. IASP Pain Terminology. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. Edinburgh, UK: Harcourt Publishers Limited ;11-57 Additional key words: descriptor 1. International Association for the Study of Pain. IASP Pain Terminology. 2. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed ;11-57

Dolor nociceptivo El dolor nociceptivo es una respuesta fisiológica apropiada a los estímulos dolorosos. Dolor Entrada ascendente Modulación descendente Asta dorsal Tracto espinotalámico Ganglio de la raíz dorsal This slide illustrates some central and peripheral pathways by which painful stimuli are normally processed (nociceptive pain). The key talking points on this slide are as follows: The receptor of peripheral nociceptors may be activated by noxious mechanical, thermal (heat and cold) or chemical stimuli. Pain impulses are then transmitted along sensory axons, contained in peripheral nerves and dorsal roots, to the dorsal horn. Peripheral nerve fibers involved in pain include unmyelinated slowly-conducting C fibers and thinly-myelinated Adelta (A) fibers. In the superficial layers of the dorsal horn they make synaptic connection with second-order neurons that transmit the impulses through the spinal cord to the brain (ascending transmission pathway). In the brain, the thalamus and certain specific cortical areas are critical for the sensory and emotional experience of pain. Transmission and processing of pain impulses is also modulated by descending (inhibitory) and segmental controls. Reference Tortora G, Grabowski SR. Principles of Anatomy and Physiology. 10th ed. New York, NY: John Wiley & Sons; 2003. Trauma Nervio periférico Nociceptores periféricos Tortora G, Grabowski SR. Principles of Anatomy and Physiology. 10th ed.2003.

Causas del dolor neuropático
Causas periféricas del dolor neuropático Trauma e.g. cirugía, atrapamiento neural, amputación Desórdenes metabólicos e.g. diabetes mellitus, uremia Infecciones e.g. herpes zoster (erupciones en la piel), HIV Toxinas e.g. agentes quimoterapéuticos, alcohol Trastornos vasculares e.g. lupus eritematoso, poliarteritis nodosa Deficiencias nutricionales e.g. niacina, tiamina, piridoxina Efectos directos del cáncer e.g. metástasis, infiltrado Causas centrales del dolor neuropátivo Accidente vascular cerebral (AVC) Lesiones de la médula espinal Esclerosis múltiple Tumores Neuropathic pain is initiated or caused by a primary lesion or dysfunction in the peripheral or central nervous system. Patients with neuropathic pain have chronic pain, which is typically considered to be pain that persists beyond the normal time of healing or for more than 3-6 months.This slide lists some of the most commonly encountered peripheral and central causes of neuropathic pain. The key points on this slide are as follows: Any type of peripheral nerve or root injury may lead to neuropathic pain: traumas, entrapments (like carpal tunnel syndrome), postsurgical iatrogenic nerve lesions, amputations, radiculopathies, etc. Metabolic disturbances may also cause neuropathies associated with neuropathic pain, most notably diabetes mellitus but also uremia and hypothyroidism. Infections such as HIV may also result in peripheral nerve damage. Toxins implicated in peripheral nerve injury include chemotherapeutic agents, lead, organophosphorates and alcohol. Glue sniffing has also been associated with neuropathic pain from peripheral neuropathy. Vascular disorders (polyarteritis nodosa, lupus erythematosus), nutritional deficiencies (niacin, thiamine, pyridoxine), and direct effects of cancer due to metastases and infiltration may also cause peripheral neuropathies leading to neuropathic pain. Central neuropathic pain may be present in about 8% of stroke patients, and in about 28% of patients with multiple sclerosis. Spinal cord lesions and tumors are also known, common causes of central neuropathic pain. References Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. Edinburgh, UK: Harcourt Publishers Limited. 1999 Galer BS, Dworkin RH (Eds). A clinical guide to neuropathic pain. Minneaplois, MN: McGraw-Hill Healthcare Information. 2000 Woolf CJ, Mannion RJ. Lancet. 1999;353: Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999; Galer BS, Dworkin RH (Eds) A clinical guide to neuropathic pain. 2000: Woolf CJ et al. Lancet. 1999;353:

La prevalencia del dolor neuropático oscila de 6.0 a 7.7% en Europa
7.5% 6.4% % de pacientes 6.0% This slide describes the results from the Neuropathic Pain Patient Flow Survey, an extensive survey conducted in the UK, France, Germany and Spain. One part of the survey included random digit dialing to 14, 986 people who were asked a series of questions about pain and medical diagnoses they had received. Any person who did not have a formal diagnosis of neuropathic pain, but who had features consistent with neuropathic pain, was reviewed by an expert to confirm the presence of absence of neuropathic pain. In total 1010/14,986 (6.7%) fulfilled criteria for neuropathic pain (which included axial back pain with a neuropathic component). The key talking points on this slide are as follows: The overall prevalence of neuropathic pain was similar across 4 large European countries ( %). This suggests that approximately 1 in 15 adults are experiencing neuropathic pain of some description at any given time.1 Although the true prevalence of neuropathic pain in the general population has been little studied, the literature suggests that only 1 to 2%2 of the general population may be affected. The results of the Neuropathic Pain Patient Flow Survey suggest that the global prevalence of neuropathic pain may be under-estimated in the literature. References Data on file, Pfizer Inc. Neuropathic Pain Patient Flow Survey Chong et al. J Pain Symptom Manage. 2003;25:S4-11. Reino Unido Francia Alemania España Pacientes con lumbalgia axial con un componente neuropático incluídos en la encuesta Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

Prevalencia/ Incidencia del dolor neuropático
20-24% de los diabéticos experimentan neuropatía diabética periférica1 dolorosa 25-50% de los pacientes > 50 años con herpes zoster desarrollan neuralgia postherpética (≥3 meses después de haberse recuperado del brote)1 Hasta un 20% desarrollan dolor posterior a la mastectomía2 Un tercio de los pacientes con cáncer tiene dolor neuropático (solo o con dolor nociceptivo)3 7% de los pacientes con lumbalgia pueden tener dolor neuropático asociado4 The true prevalence of neuropathic pain in the general population is unknown because of a lack of large scale epidemiological studies. Current estimates suggest that up to 2% of the general population may be affected5, but this is likely to be an underestimate. This slide presents prevalence/incidence data from individual studies that have been conducted in different patient populations, including those with diabetes and cancer. The key talking points on this slide are as follows: Neuropathic pain is prevalent among patients with diabetes and following herpes zoster infection (shingles).1 Up to one quarter of patients with diabetes mellitus experience painful DPN; increased age, duration of diabetes, and poorer glycemic control are all thought to increase the risk of painful DPN.1 It has been estimated that around half of all patients (aged >50 years) with herpes zoster will be experiencing PHN at 3 months if they do not receive antiviral therapy.1 Even with antiviral treatment, 25% of these patients will experience PHN at 3 months. Post-mastectomy pain (a distinctive post-surgical neuropathic pain syndrome) may occur in 20% of women who have had a mastectomy.2 Neuropathic pain occurs in one-third of patients with cancer.3 Among patients with low back pain, 7% are estimated to have neuropathic pain (herniated disc or spinal stenosis)4 References Schmader. Clin J Pain. 2002;18:350-4. Stevens et al. Pain. 1995;61:61-8 Davis and Walsh. Am J Hosp Palliat Care. 2004;21(2): Deyo and Weinstein. NEJM 2001;344(5):363 – 370 Chong et al. J Pain Symptom Manage. 2003;25:S4-11 Additional key words: diabetic 1. Schmader. Clin J Pain. 2002;18: Stevens et al. Pain. 1995;61:61-8 3. Davis and Walsh. Am J Hosp Palliat Care. 2004;21(2): 4. Deyo and Weinstein. NEJM 2001;344(5):

Signos y síntomas del dolor neuropático
Signo/ síntoma Descripción (ejemplo) Síntomas espontáneos Dolor espontáneo1 Ardor persistente, dolor intermitente similar a choque o punzada de lanza Disestesias2 Sensaciones desagradables anormales, e.g. disparo, punzada de lanza, ardor Parestesias2 Sensaciones anormales no desagradables, e.g. hormigueo Síntomas evocados por estímulos Alodinia2 Respuesta dolorosa a estímulos no dolorosos e.g. calor, presión, golpe Hiperalgesia2 Respuesta intensificada a estímulos dolorosos e.g. punzada, frío, calor Hiperpatia2 Respuesta explosiva, retardada a cualquier estímulo doloroso This slide describes the type of pain associated with the two broad categories of neuropathic pain signs and symptoms: spontaneous (also termed stimulus-independent) and stimulus-evoked symptoms. The key talking points on this slide are as follows: Spontaneous pain is the most frequent symptom in all painful neuropathies and presents with a burning quality, localized superficially, or electric shock-like pain for several seconds. Dysesthesias are abnormal sensations that are unpleasant, and include shooting, lancinating (piercing/stabbing) or burning pains. Paresthesias are abnormal sensations that are not unpleasant, such as tingling. Symptoms of stimulus-evoked pain can be described according to the nature of the provoking stimulus, i.e. whether it is usually pain-free and innocuous, or painful and noxious. Allodynia is a painful response to a stimulus that is not normally painful. Hyperalgesia is a heightened response to a stimulus that would normally evoke pain. Hyperpathia is a painful syndrome characterized by an abnormally delayed painful reaction to a stimulus, especially a repetitive stimulus. References Baron. Clin J Pain. 2000;16:S12-S20. Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994:

¿Cómo describiría usted el dolor? (n=1172)
Descripciones de los síntomas reportados por los pacientes con dolor neuropático* ¿Cómo describiría usted el dolor? (n=1172) % de respuestas Sordo This slide describes the results from the Neuropathic Pain Patient Flow Survey, an extensive survey conducted in the UK, France, Germany and Spain, which involved 1230 physicians and 1172 patients with confirmed neuropathic pain (including axial back pain with a neuropathic component). The survey used both qualitative research (in-depth interviews with patients and physicians and focus groups) and quantitative research (interviews and case reviews with pain clinicians and patient questionnaires) to assess issues relating to the management of neuropathic pain. Patients with neuropathic pain were asked how they would describe their pain. The first 3 descriptors mentioned by each patient were recorded and those reported by >5% of patients overall are shown on the slide. The key talking points on this slide are as follows: Patients with neuropathic pain described their pain in a wide variety of ways. ‘Lancinating’ (piercing/stabbing), ‘sharp’, ‘shooting’ and ‘burning’ were common descriptors of neuropathic pain in this survey.1 While ‘aching’, ‘dull’ and ‘cramping’ are not typically considered as neuropathic pain symptoms, their mention in conjunction with neuropathic pain symptoms reflects the existence of mixed pain states in this sample. References Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey Agudo Profundo Adolorido Ardiente Cortante Disparo Radiante Entumecido Estallido Calambre Penetrante Apuñalamiento Taladramiento Carcomiendo Punzada de lanza Alfileres y agujas *Incluye estados de dolor periférico, central y mixto Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey.

Los médicos generales son cruciales en el manejo del dolor neuropático
Los médicos generales son cruciales en el manejo y tratamiento del dolor neuropático1 La mayoría de los pacientes primero consultan a su médico general Aproximadamente 50% de los pacientes son manejados por médicos generales A pesar de la alta prevalencia de dolor crónico visto por los médicos generales, únicamente una pequeña proporción de todos los pacientes vistos por dichos médicos tienen dolor neuropático Los médicos generales se enfrentan más al desafío de reconocer el dolor neuropático Se requiere una mejor educación sobre el dolor This slide describes the results from the Neuropathic Pain Patient Flow Survey, an extensive survey conducted in the UK, France, Germany and Spain, which involved 1230 physicians and 1172 patients with confirmed neuropathic pain (including axial back pain with a neuropathic component). The survey used both qualitative research (in-depth interviews with patients and physicians and focus groups) and quantitative research (interviews and case reviews with pain clinicians and patient questionnaires) to assess issues relating to the management of neuropathic pain. As part of the survey, 1056 patients with neuropathic pain provided responses about what type of doctor they first visited for their pain and what type of doctor was responsible for managing their pain at the time of the survey. 428 general practitioners (GPs) were asked how easy they found it to recognize neuropathic pain. The key talking points on this slide are as follows: GPs play a key role in the diagnosis and management of neuropathic pain. Three-quarters (75%) of patients first consulted their GP for their pain. Over half (54%) were being managed by their GP at the time of the survey. Despite the high prevalence of chronic pain among patients seen by the GPs surveyed (24% of all patients) only one-quarter of chronic pain patients were reported by GPs to have neuropathic pain. Thus, in this sample neuropathic pain patients only represented 6% of all patients seen by the GPs surveyed. GPs admit to finding it difficult to recognize neuropathic pain. There is a clear need for enhanced education of GPs and other non-pain specialists to improve the recognition and diagnosis of neuropathic pain. References 1. Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey 2. Harden and Cohen. J Pain Symptom Manage. 2003;25 (5S)S12-S17 1. Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

EUROPEAN BURDEN OF ILLNESS SURVEY
Selección al azar, estudio observacional, auto-reporte de la salud y el bienestar de los pacientes, experiencia del dolor, el uso de medicamentos y los problemas relacionadas con el tratamiento. La encuesta se realizó en 602 pacientes con dolor neuropático, condiciones de consulta por los médicos generales no especializados en dolor en 6 países europeos (Francia, Alemania, Italia, Países Bajos, España y Reino Unido). En total, 600 pacientes respondieron a la duración de su dolor neuropático. Los médicos reclutaron pacientes que presentaron una visita clínica regularmente programada. Los pacientes deben haber experimentado dolor neuropático debido a uno de los 10 estados de dolor neuropático, se define de estudio en los últimos 7 días. Los pacientes con dolor lumbar se excluyeron de la encuesta para asegurarse de que sólo los pacientes con dolor neuropático claramente definidos fueron incluidos. La edad media de la población de pacientes era de 63 años, con un 50% de los participantes ≥ 65 años de edad. igual número de hombres y mujeres fueron reclutados. CONCLUSIONES las personas con dolor neuropático sufren a menudo por largos períodos de tiempo. Dos tercios de los pacientes que participan en la encuesta (67%) había estado sufriendo de dolor neuropático por más de 1 año. 43% de los pacientes había estado sufriendo de dolor neuropático por más de 3 años

Duración de las condiciones del dolor neuropático
67% de los pacientes tuvo dolor neuropático por más de 1 año N=600 % de los que respondieron This slide shows results from the European Burden of Illness Survey, which was a cross-sectional, observational, one-time survey of patient self-reported health and well-being, pain experience, medication use and related treatment issues. The survey was conducted in 602 subjects with painful neuropathic conditions recruited by general practitioners and non-pain specialists in 6 European countries (France, Germany, Italy, The Netherlands, Spain and the UK). In total, 600 patients provided responses on the duration of their neuropathic pain. Physicians recruited patients as they presented for a regularly clinic scheduled visit. Patients must have experienced neuropathic pain due to one of 10 study-defined neuropathic pain conditions in the previous 7 days. Patients with low back pain were excluded from the survey to ensure that only those patients with clearly defined neuropathic pain were included. The mean age of the patient population was 63 years, with 50% of participants ≥65 years old. Equal numbers of men and women were recruited. The most frequent neuropathic pain conditions were DPN (23% of participants), PHN (14%), cervical radiculopathy (14%), trigeminal neuralgia (14%) and post traumatic neuropathy (12%). The key talking points on this slide are as follows: This survey confirmed that individuals with neuropathic pain often suffer for long periods of time. Two-thirds of patients involved in the survey (67%) had been suffering from neuropathic pain for more than 1 year. 43% of patients had been suffering from neuropathic pain for more than 3 years. Reference Data on file. Pfizer Inc. European Survey in Painful Neuropathic Disorders Additional key words: diabetes, diabetic, postherpetic 3 a 6 7 a 12 13 a 35 Meses con dolor neuropático

Interrelación entre el dolor, sueño y ansiedad /depresión
Deterioro funcional Patients who suffer from chronic pain experience difficulties initiating and maintaining sleep and are often depressed and anxious. The inter-relationship between these three factors, as shown on this slide, is complex, but must be considered carefully if treatment for neuropathic pain is to be satisfactory. The key talking points on this slide are as follows: Although most pain disorders begin with injury or disease, their course and outcome are affected by emotional, behavioral and social factors. An individual’s emotional reaction to, and capacity to cope with, the fluctuating course of neuropathic pain disorders and their complications such as physical impairment, disability, and loss of role functioning will also affect outcome. Chronic pain significantly interferes with sleep, with most studies showing a positive correlation between pain intensity and degree of sleep disturbance. Many chronic pain patients have signs and symptoms of depression and anxiety; sleep deprivation can lead to anxiety, and depression can be both the cause and result of sleep deprivation. Chronic pain, sleep disturbances, and depression/anxiety must be addressed if patients are to be restored to optimal functionality. Physicians must evaluate all aspects of pain, sleep and mood in patients with chronic pain. Management and treatment should address both the pain and the comorbidities, to improve daily functioning, and enhance quality of life. Reference Nicholson and Verma. Pain Med. 2004;5(suppl. 1):S9-S27 Additional key words: mood Ansiedad y depresión Molestias en el sueño Nicholson and Verma. Pain Med. 2004;5 (suppl. 1):S9-S27

Los pacientes con dolor neuropático periférico experimentan síntomas comórbidos significativos
Dificultad en el sueño Falta de energía Adormecimiento Dificultades en la concentración Depresión Ansiedad Poco apetito This study was undertaken to assess the health-related quality of life and burden of illness due to pain and its treatment in 126 patients with neuropathic pain due to a peripheral nerve or root lesion. Patients were recruited from 2 multidisciplinary pain clinics in Sweden. Patients were asked to rate the extent to which they were bothered by 25 pain-related symptoms and/or side-effects of drug treatment during the previous week (rated as 1=no discomfort to 7=very severe discomfort). This slide shows the proportions of patients who rated their discomfort as 4 (moderate) to 7 (very severe). Data on 7 of the 10 most frequently reported comorbid symptoms are shown on the slide. Overall, 88% of patients reported some degree of discomfort associated with their pain or its treatment. The key talking points on this slide are as follows: Difficulty sleeping was the most bothersome symptom and was moderate to very severe in 60% of patients. A lack of energy, drowsiness, and difficulty in concentrating, were also troubling for many individuals. Moderate to very severe levels of depression were reported by 35% (1 in 3 patients), and anxiety by 27% (1 in 4 patients) These data indicate that sleep disturbance, anxiety and depression and related symptoms are prevalent among patients with peripheral neuropathic pain. Reference Meyer-Rosberg et al. Eur J Pain. 2001;5: Additional key words: mood % de pacientes con molestia moderada a muy severa (n = 126) Meyer-Rosberg et al. Eur J Pain. 2001;5:

La ansiedad y la depresión son prevalentes en el dolor crónico
283 pacientes evaluados en centros para el dolor1 63% con síntomas de ansiedad significativos (DSM-III) 56% con síntomas depresivos significativos (DSM-III) Depresión 71 pacientes con lumbalgia crónica2 44% con depresión mayor, 11% menor (SADS-L) This slide reviews the results of 2 studies that have investigated the prevalence of anxiety and depression in patients with chronic pain (of different aetiologies) using validated psychiatric assessment instruments. In the study by Fishbain et al,1 283 chronic pain patients who were admitted consecutively to a pain center were evaluated using DSM-III criteria. In the study by Krishnan et al,2 71 patients with chronic low back pain were evaluated using the SADS-L criteria. The key talking points on this slide are as follows: Both anxiety and depression are common comorbidities in patients with chronic pain. In these studies, significant depressive symptoms were apparent in over 50% of individuals with chronic pain. Significant anxiety symptoms were found in over 60% of patients with chronic pain.1 Anxiety and depression in these patients may stem from the stressful negative consequences of living with pain (e.g. interference with work, relationships, and hobbies), as well as knowing that they have a painful condition with no particular treatable cause and no apparent way to obtain relief.3 Anxiety and depression may also result from sleep deprivation caused by pain-related sleep interference.3 Abbreviations: DSM-III: Diagnostic and Statistical Manual of Mental Disorders III; SADS-L: Schedule for affective disorders and schizophrenia – Lifetime version References Fishbain et al. Pain. 1986;26(2): Krishnan et al. Pain. 1985;22(3): Nicholson and Verma. Pain Med. 2004;5(suppl. 1):S9-S27 Additional key words: mood 1.Fishbain DA et al. Pain 1986;26: 2.Krishnan KR et al. Pain 1985;22:

Pacientes con neuropatía diabética periférica tienen un deterioro funcional
Deterioro en la puntuación del Inventario Breve Modificado del dolor 5 Social Recreación Cuidado propio Disfrute Sueño Relaciones Trabajo normal Movilidad Estado de ánimo General In this survey of 105 patients with painful diabetic peripheral neuropathy (DPN ) patients were asked to complete the 10-item modified Brief Pain Inventory (mBPI), which required patients to rate the extent to which pain interfered with their daily activities, mood, normal work, relations with other people, sleep, enjoyment of life, self care, recreational and social activities during the previous week. Response categories ranged from 0 (did not interfere) to 10 (completely interfered). A score of 5 was considered an indication of substantial interference with activities because of pain. This slide reflects domains for which interference in function was substantial i.e. score 5. In this survey, the average age of respondents was 63 years; first onset of neuropathic pain was at the mean age of 57 years. The key talking points on this slide are as follows: A substantial proportion of patients reported that pain interfered with function in each of the 10 domains assessed (35-58%). Over half the patients reported substantial impairment in social and recreational activities, enjoyment of life, mobility and being able to work normally. Almost 60% reported that pain substantially interfered with sleep. Over 40% reported that pain substantially affected their mood. The results of this survey demonstrate that DPN has a definite and measurable negative impact on patient quality of life. Reference Galer et al. Diabetes Res Clin Pract. 2000;47(2): % de pacientes con interferencia substancial en función (n =105) Galer et al. Diabetes Res Clin Prac 2000;47:

La mayor parte del tiempo Una pequeña parte del tiempo
Disminución en la productividad laboral las últimas 4 semanas debido a pacientes con dolor neuropático 80% de los pacientes que trabajan había disminuido la productividad laboral debido a su dolor neuropático Todo el tiempo 17% Ningún tiempo 20% La mayor parte del tiempo 6% Buena parte del tiempo 7% Una pequeña parte del tiempo 27% This slide shows results from the European Burden of Illness Survey, which was a cross sectional, observational, one-time survey of patient self-reported health and well-being, pain experience, medication use and related treatment issues. The survey was conducted in 602 subjects with painful neuropathic conditions recruited by general practitioners and non-pain specialists in 6 European countries (France, Germany, Italy, The Netherlands, Spain and the UK). Physicians recruited patients as they presented for a regularly clinic scheduled visit. Patients must have experienced neuropathic pain due to one of 10 study-defined neuropathic pain conditions in the previous 7 days. Patients with low back pain were excluded from the survey to ensure that only those patients with clearly defined pain were included. The mean age of the patient population was 63 years, with 50% of participants ≥65 years old. Equal numbers of men and women were recruited. The most frequent neuropathic pain conditions were DPN (23% of participants), PHN (14%), cervical radiculopathy (14%), trigeminal neuralgia (14%) and post traumatic neuropathy (12%). The patient questionnaire included a question on the impact of neuropathic pain on work productivity for patients who were employed (n=109). The key talking points on this slide are as follows: As part of this survey, employed individuals were asked if they had reduced productivity at work during the previous 4 weeks. 80% of respondents who were employed reported some degree of working productivity loss; over 20% of respondents reported that their productivity was reduced most or all of the time. In addition to reporting reduced productivity at work, participants had also missed an average of 5.5 days’ work during the previous 4 weeks. This survey has confirmed that the indirect costs associated with neuropathic pain in terms of lost work productivity are substantial. Reference Data on file. Pfizer Inc. European Survey in Painful Neuropathic Disorders Additional key words: resource Poco tiempo 23% N=109 laboran Data on file, Pfizer Inc. European Survey in Painful Neuropathic Disorders

Revisión del dolor neuropático: Resumen
El dolor neuropático es una condición compleja: La prevalencia puede ser reportada incorrectamente El diagnóstico puede ser difícil Puede estar asociado con dolor debilitante A menudo asociado con alteraciones en el sueño, ansiedad y depresión A menudo asociado con discapacidad y disminución en la calidad de vida Tratamientos actuales para el dolor neuropático: A menudo apoyados por evidencias variables Pueden ser sin efecto o pobremente tolerados Es conveniente mejorar la comprensión de los médicos y nuevas opciones de tratamiento The key talking points on this slide are as follows: In summary, neuropathic pain represents a healthcare challenge. Its complex etiology and variable symptomatology make neuropathic pain difficult to diagnose, especially for GPs. The pain associated with the condition is often severe, and many patients experience debilitating pain despite receiving treatment. The severity and chronic nature of neuropathic pain have an important impact on the well-being of sufferers; many patients experience sleep disturbances and functional impairments, and many have comorbid anxiety and depression. The most commonly prescribed medications for the treatment of neuropathic pain (NSAIDs) are known to be ineffective in many patients. Two classes of drugs that have demonstrated efficacy in neuropathic pain (AEDs and antidepressants) represent a relatively small proportion of all medications prescribed to patients with neuropathic pain. In addition, these agents are not always effective and nor always well tolerated. Better education of GPs and other non-pain specialists, to enhance understanding, is recommended. Physicians should learn to recognize and diagnose neuropathic pain more confidently. New and better medications for neuropathic pain are clearly required. Additional key words: symptom, comorbid, mood, quality of life

Definiendo el dolor ¿Qué es el dolor?
“Una experiencia sensorial y emocional desagradable asociada con un daño tisular actual o potencial, o descrito en términos de dicho daño.” Asociación Internacional para el Estudio del Dolor (IASP) 1994 The Task Force on Taxonomy Committee of the International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” This definition of pain allows us to understand that pain is not only a sensory experience but also an emotion that can affect quality of life. Reference Merskey H, Bogduk N, eds. In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 2nd ed. Seattle, Wash: IASP Press; 1994: Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994:

Clasificaciones del dolor
Agudo Duración Crónico Nociceptivo There are a variety of approaches for classifying pain. The two that are used most frequently are based on pain duration (i.e. acute vs chronic pain) and underlying pathophysiology (i.e. nociceptive vs. neuropathic pain). Fisiopatología Neuropático

La continuación del dolor1
Insulto Tiempo hasta la resolución Dolor agudo Dolor crónico <1 mes 3-6 meses Daño tisular usualmente obvio Aumento en actividad del sistema nervioso El dolor se resuelve con la curación Sirve como una función protectora Dolor por 3-6 meses o más2 Dolor más allá del período de curación esperado2 Usualmente no tiene ninguna función protectora3 Deteriora la salud y el funcionamiento3 This slide illustrates how acute and chronic pain are often classified along a pain continuum.1 The key talking points on this slide are as follows: Acute pain may be seen as a message that follows an insult to tissue, signaling the presence of a pathologic condition, thus alerting the patient to the need to either seek treatment or protect the involved area from further injury. Some episodes of acute pain are self-limiting. Acute pain becomes chronic when it persists 3 to 6 months after onset or beyond the expected period of healing.2 Chronic pain has also been defined as pain that ceases to serve a protective function, and instead degrades health and functional capability.3 Chronic pain conditions may be associated with nociceptive pain only, a combination of nociceptive pain and neuropathic pain, or neuropathic pain only. It is important to differentiate chronic pain from a condition with recurrent episodes of acute pain because the treatment strategies are very different for these 2 situations. References 1.Cole BE. Hospital Physician. 2002;38:23-30. 2.Turk and Okifuji. Bonica’s Management of Pain 3.Chapman and Stillman. Pain and Touch 1. Cole BE. Hosp Physician. 2002;38:23-30. 2.Turk and Okifuji. Bonica’s Management of Pain 3. Chapman and Stillman. Pain and Touch

Dolor neuropático periférico Dolor neuropático central
Definiciones de la IASP: Dolor neuropático periférico y neuropático central Dolor neuropático Dolor iniciado o causado por una lesión primaria o disfunción en el sistema nervioso central Dolor neuropático periférico Dolor iniciado o causado por una lesión primaria o disfunción en el sistema nervioso periférico Dolor neuropático central Dolor iniciado o causado por una lesión primaria o disfunción en el sistema nervioso central This slide presents the current definitions of neuropathic pain from the International Association for the Study of Pain (IASP). The IASP first published its pain terms in 1979, however, neuropathic pain was not included in the list until The key talking points on this slide are as follows: The IASP’s definition of neuropathic pain as ‘pain initiated or caused by a primary lesion or dysfunction in the nervous system’ is a broad definition that encapsulates the concept that, as the nervous system is damaged, there may appear changes in the nervous system that could result in chronic pain, even in the absence of a damaging insult. Although this theory has now gained general acceptance, it was originally a revolutionary idea that repudiated the Cartesian model of nociception and pain.2 Depending on where the lesion or dysfunction occurs in the nervous system, neuropathic pain can be peripheral or central in origin. References Merskey H, Bogduk N, eds. In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 2nd ed. Seattle, Wash: IASP Press; 1994: Chong and Bajwa. J Pain Symptom Manage. 2003;25:S4-S11 Cruccu et al. EFNS guidelines on neuropathic pain assessment. Eur J Neurol. 2004;11(3): Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994:

La presentación entre los estados del dolor varía
Dolor neuropático Dolor iniciado o causado por una lesión primaria o disfunción en el sistema nervioso (sistema periférico o nervioso central1 Dolor mixto Dolor con componentes neuropáticos y nociceptivos Dolor nociceptivo Dolor causado por lesión a tejidos corporales (musculoesqueléticos, cutáneos o viscerales)2 This slide illustrates three broad categories of pain: neuropathic (pathologic), nociceptive (physiologic), and mixed pain states that encompass both nociceptive and neuropathic components, with examples of common causes of each type of pain. The key talking points on this slide are as follows: Neuropathic pain has been defined by the International Association for the Study of Pain as ‘initiated or caused by a primary lesion or dysfunction in the nervous system’.1 Depending on where the lesion or dysfunction occurs within the nervous system, neuropathic pain can be peripheral or central in origin. Nociceptive pain is an appropriate physiologic response that occurs when specific peripheral sensory neurons (nociceptors) respond to noxious stimuli. Nociceptive pain has a protective role because it elicits reflex and behavioral responses that keep tissue damage to a minimum. There are cases in which an individual experiences pain sensations that are a blend of pain having a nociceptive and a neuropathic origin. For example, in carpal tunnel syndrome, it is common experience to have nociceptive pain, felt around the wrist, and neuropathic pain, felt in the distribution territory of the median nerve (fingers). References International Association for the Study of Pain. IASP Pain Terminology. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. Edinburgh, UK: Harcourt Publishers Limited ;11-57 1. International Association for the Study of Pain. IASP Pain Terminology. 2. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed ;11-57

Desarrollo del dolor neuropático
Síndrome Dolor neuropático Síntomas Dolor espontáneo Dolor evocado por los estímulos Fisiopatología Mecanismos Metabólico Traumático Tóxico Isquémico Hereditario Compresión Infeccioso Inmuno relacionado Etiología This slide illustrates the concept that many different underlying causes of neuropathic pain may express as different spontaneous and stimulus-evoked pain symptoms via different pathophysiological mechanisms. The key talking points on this slide are as follows: There are many possible causes of neuropathic pain. Neuropathic pain is commonly classified according to the etiological nature of the damage to the nervous system or the anatomical distribution of the pain, although the relationship between etiology, mechanisms, and symptoms/signs is highly complex. For instance, the pain caused by diverse diseases may originate through common mechanisms also one mechanism could be responsible for many different symptoms conversely, the same symptom in 2 patients may be caused by different mechanisms furthermore, more than one mechanism can operate in a single patient, and the pattern of mechanisms and symptoms within a single patient may change with time. No pain pathophysiological mechanism is an inevitable consequence of a particular disease process. Studies are needed to further define pathophysiological mechanisms of neuropathic pain. Reference Woolf and Mannion. Lancet 1999;353: Additional key words: pathophysiology Daño nervioso Woolf and Mannion. Lancet 1999;353:

Dolor nociceptivo El dolor nociceptivo es una respuesta fisiológica apropiada al estímulo doloroso Dolor Entrada ascendente Modulación descendente asta dorsal Tracto espinotalámico Ganglio de la raíz dorsal This slide illustrates some central and peripheral pathways by which painful stimuli are normally processed (nociceptive pain). The key talking points on this slide are as follows: The receptor of peripheral nociceptors may be activated by noxious mechanical, thermal (heat and cold) or chemical stimuli. Pain impulses are then transmitted along sensory axons, contained in peripheral nerves and dorsal roots, to the dorsal horn. Peripheral nerve fibers involved in pain include unmyelinated slowly-conducting C fibers and thinly-myelinated Adelta (A) fibers. In the superficial layers of the dorsal horn they make synaptic connection with second-order neurons that transmit the impulses through the spinal cord to the brain (ascending transmission pathway). In the brain, the thalamus and certain specific cortical areas are critical for the sensory and emotional experience of pain. Transmission and processing of pain impulses is also modulated by descending (inhibitory) and segmental controls. Reference Tortora G, Grabowski SR. Principles of Anatomy and Physiology. 10th ed. New York, NY: John Wiley & Sons; 2003. Trauma Nervio periférico Nociceptores periféricos Tortora G, Grabowski SR. Principles of Anatomy and Physiology. 10th ed.2003.

Tipos de fibras involucrados en el dolor neuropático
Fibras Aβ Diámetro grande, mielinizadas, velocidad de conducción rápida Mecanorreceptores activados normalmente por estímulos mecánicos no nocivos (tacto) Fibras Aδ Diámetro grande, mielinizadas, velocidad de conducción intermedia Normalmente activadas por estímulos nocivos (transmiten dolor agudo) Fibras C Diámetro pequeño, no mielinizadas, velocidad de conducción lenta Normalmente activadas por estímulos nocivos (responsables por dolor secundario, normalmente ardor, dolor constante) En el dolor neuropático las sensaciones anormales pueden ser transmitidas a lo largo de las fibras Aβ , Aδ o C One of the vital functions of the nervous system is to provide information about the occurrence or threat of injury. Highly specialized sensory neurons provide information to the central nervous system about both the environment and the organism itself. This slide describes the three main types of sensory fibers that may be implicated in the generation of neuropathic pain signs and symptoms. The key talking points on this slide are as follows: Nociception (the perception of noxious stimuli) is initiated by stimuli that activate the peripheral receptors of nociceptors, a highly specialized set of sensory neurons that respond only to damaging or potentially stimuli. Nociceptors have unmyelinated (C fibers) or thinly myelinated (A-delta fibers) axons. Abeta (Aβ) fiber mechanoreceptors respond to non-noxious mechanical stimuli. Adelta (Aδ) and C fibers nociceptors are usually activated by noxious stimuli. All three types of sensory fibers may be involved in the production of neuropathic pain. References Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. Edinburgh, UK: Harcourt Publishers Limited 1999;11-57 Dworkin. Clin J Pain. 2002;18: Additional key words: pathophysiology Dworkin Clin J Pain. 2002;18: Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed ;11-57

Dolor neuropático: Mecanismos fundamentales
Mecanismos periféricos Hiperexcitabilidad de la membrana Descargas ectópicas Sensibilización periférica Mecanismos centrales Hiperexcitabilidad de la membrana Descargas ectópicas Fenómeno “Wind up” Sensibilización central Supersensivilidad por denervación Pérdida de controles inhibitorios This slide illustrates the main mechanisms underlying the development of neuropathic pain. The key talking points on this slide are as follows: By definition, neuropathic pain occurs following a primary lesion or dysfunction in the peripheral or central nervous system. These lesions and/or dysfunctions trigger the underlying mechanisms that result in neuropathic pain. Peripheral mechanisms of neuropathic pain include membrane hyperexcitability (which may lead to ectopic discharges along sensory nerves) and peripheral sensitization. Central mechanisms include hyperexcitability, wind up, central sensitization, denervation supersensitivity and loss of inhibitory controls. These mechanisms will be described in the following slides. More than one mechanism may be involved in the symptoms experienced by an individual patient and the mechanisms involved may change over time, which can complicate treatment decisions. Note: Another proposed mechanism underlying neuropathic pain is central reorganization of A beta (A) fibers. A fibers normally transmit sensations relating to nonpainful touch. However, following peripheral nerve injury, nerve fibers degenerate and then regenerate in the presence of various nerve growth factors. In animal models, A fibers sprout into the superficial dorsal horn, an area that normally mediates pain perception following noxious input from the periphery via C fibers. During these animal studies, when this portion of the dorsal horn was stimulated by A fiber terminals following non-noxious stimuli, behavior of the animals was consistent with pain. However, it is not clear how these animal models apply to humans, where other mechanisms might be involved. While this hypothesis has received considerable support in the past, recent research suggests that this explanation may no longer be valid. References Attal N et al. Acta Neurol Scand. 1999;173: Woolf CJ et al. Lancet. 1999;353: England JD et al Neurology. 1996;47: Ochoa & Torebjork. Brain. 1980;103: Siddall PJ, Cousins MJ. Spine. 1997;22:98-104; Victor M, Ropper AH (Eds). Principles of Neurology. 7th ed. New York, NY: McGraw-Hill; 2001; Doubell et al. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed. Edinburgh, UK: Harcourt Publishers Limited; 1999; Mannion RJ, Woolf CJ. Clin J Pain. 2000;16:S Roberts MTH, Rees H. In Casey KL (Ed) Pain and Central nervous system disease. New York, NY:Raven Press, 1991. Additional key words: pathophysiology Attal N et al. Acta Neurol Scand. 1999;173: Woolf CJ et al. Lancet. 1999;353: Roberts et al. In Casey KL (Ed). Pain and central nervous system disease. 1991

Proceso sensorial y dolor neuropático
Función nerviosa Estímulo Aferente primario Sensación Mecanismo Normal Inofensivo, mecánico A-beta Tacto normal Función normal Nocivo, mecánico, térmico o químico Nociceptor A-delta nociceptor C Dolor agudo normal Dolor ardiente normal Reducida Hipoanestesia táctil Disminución en la transmisión de impulsos Nocivo, térmico o químico mecánico Hipoalgesia mecánica, calor o frío Incrementada Alodinia mecánica dinámica Muchas teorías (sensibilización, etc.) Hiperalgesia mecánica, calor o frío Muchas teorías (wind-up, sensibilización periférica, etc.) This slide describes sensations in response to innocuous and noxious stimuli under conditions of normal nerve function, decreased nerve function in damaged nerves and increased nerve function in damaged nerves. key talking points on this slide are as follows: When nerves are not damaged and functioning normally, innocuous mechanical stimuli (e.g. rubbing your face) result in transmission by A-beta fibers and the resulting sensation is normal touch. If undamaged nerves are subject to noxious stimuli (e.g. pinprick, burn by a candle or a strong acid), resulting transmission by A-delta nociceptors and C nociceptors, results in sensations of normal sharp and burning pain, respectively. When nerves are damaged and their function is decreased, innocuous mechanical stimuli result in decreased transmission of impulses along A-beta fibers with resultant tactile hypoanesthesia (little or no feeling). When damaged nerves with decreased function are exposed to noxious stimuli, transmission or impulses along A-delta and C nociceptors is decreased with resultant hyopalgesia (lack of an appropriate painful sensation) When nerves are damaged and their function is increased, innocuous mechanical stimuli result in dysfunction of A-beta fibers with resultant dynamic mechanical allodynia (a sensation of pain when it is not appropriate). When damaged nerves with increased function are exposed to noxious stimuli result in dysfunction of A-delta and C nociceptors with resultant hyperalgesia (an increased pain response beyond that expected for the level of stimulus). The precise mechanisms that underlie the dysfunction in damages nerves with increased function are not yet fully understood. However, several theories have been proposed and these include peripheral and central sensitization and wind-up. Reference Adapted from Doubell et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.; Additional key words: pathophysiology Adapted from Doubell et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed ;

Mecanismos Centrales Dolor neuropático

Neuronas del asta dorsal
Fenómeno “Wind-up” Descargas aferentes repetitivas en las fibras-C inducen a descargas en las neuronas del asta dorsal en frecuencias progresivamente mayores Estímulos Estímulos Wind up in which repetitive afferent barrages in C-fibers induce discharges of dorsal horn neurons at progressively greater frequencies. Key points on this slide are as follows: Central mechanisms may play a role in the development of neuropathic pain. Repetitive stimulation of peripheral nociceptors may cause repetitive impulse propagation along C fibers. This repetitive volley of impulses leads to the depolarization of the membrane of the dorsal horn neuron and propagation of the pain impulse to the brain. The response elicited in the dorsal horn neuron may increase with continued C-fiber input. This progressive increase in the response of the dorsal horn neuron is perceived as an increasing pain sensation and is referred to as wind up. After the incoming impulses have ceased, the dorsal horn neurons continue to fire and transmit pain impulses to the brain. References: Doubell TP, Mannion RJ, Woolf CJ. The dorsal horn: state-dependent sensory processing, plasticity and the generation of pain. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed. Edinburgh, UK: Harcourt Publishers Limited; 1999. Mannion RJ, Woolf CJ. Pain mechanisms and management: a central perspective. Clin J Pain. 2000;16:S Siddall PJ, Cousins MJ. Spine update: spinal pain mechanisms. Spine. 1997;22: Fibras nerviosas aferentes primarias Neuronas del asta dorsal

“Ciática”: Estado mixto del dolor con varios mecanismos patológicos posibles
Componente nociceptivo: Brote de fibras-C dentro del disco Disco Fibra C Componente neuropático I: Daño a una rama de la fibra C debido a compresión y mediadores inflamatorios Fibra C Fibra A Componente neuropático II: Compresión de raíz nerviosa This slide demonstrates the concept of mixed pain, using sciatica (lumbar radiculopathy) as an example of the mechanisms that can underpin the co-existence of nociceptive and neuropathic pain. Key points on this slide are as follows: The nociceptive, or “physiologic” and protective pain component arises when C fibres sprout into the disc. In addition to the nociceptive pain, there are several possible pathological events that can lead to the development of neuropathic pain. These include damage to the C fiber via compression and the release of inflammatory mediators, compression of the nerve root itself in the dorsal horn, and damage to the nerve root by inflammatory mediators. The damage to the C fiber can result in central sensitization and the perpetuation of neuropathic pain. Reference Baron R, Binder A Orthopade. 2004;33(5):568-75 Additional key words: pathophysiology Componente neuropático III: Daño a raíz nerviosa por mediadores inflamatorios Sensibilización central Baron R, Binder A Orthopade. 2004;33(5):568-75

Signos y síntomas del dolor neuropático

Definiciones de la IASP
Término del dolor Definición Alodinia Dolor debido a un estímulo que normalmente no provoca dolor Analgesia Ausencia de dolor en respuesta a la estimulación que normalmente sería dolorosa Hiperalgesia Un aumento en la respuesta a un estímulo que es normalmente doloroso Hiperestesia Aumento en la sensibilidad a la estimulación, excluyendo sentidos especiales Hiperpatía Un síndrome doloroso caracterizado por una reacción dolorosa anormalmente a un estímulo, especialmente un estímulo repetitivo, así como un aumento en el umbral Hipoalgesia Reducción del dolor en respuesta a un estímulo normalmente doloroso Hipoestesia Reducción en la sensibilidad a la estimulación, excluyendo los sentidos especiales The International Association for the Study of Pain (IASP) was founded in 1973 and first published its list of pain terms in The list was updated in 1994, and this slide shows a selection of pain terms from that 1994 update. The key talking points on this slide are as follows: Pain is divided into two broad categories: spontaneous pain (also termed stimulus-independent pain), which is present in the absence of any stimulation, and stimulus-evoked pain (also termed stimulus-dependent pain). The pain terms shown on this slide are all used to describe stimulus-evoked pain. As can be seen from this slide, the different types of stimulus-evoked pain include ‘allodynia’, which is a pain in response to a normally non-painful stimulus, and ‘hyperalgesia’, which is increased pain in response to a normally painful stimulus. The stimuli that may be used in evaluating stimulus-evoked pain include mechanical (dynamic and static) and thermal (heat and cold). Dynamic mechanical allodynia can be elicited by lightly moving a paint brush or cotton swab across the skin, static mechanical allodynia can be elicited by a light blunt pressure with a finger, and thermal allodynia can be assessed by brief application of a warmed or cooled tuning fork. Reference Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994: Additional key words: sign, symptom Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994: IASP = Asociación Internacional para el Estudio del Dolor

Signos y síntomas sensoriales positivos y negativos del dolor neuropático
Signos y síntomas sensoriales negativos Disestesias Parestesias Dolor espontáneo* Dolor evocado por estímulos Pérdida / deterioro de calidad sensorial Insensibilidad y disminución en la sensación Neuropathic pain patients commonly express a variable combination of positive and negative signs and symptoms. As shown on this slide, negative symptoms include loss of motor, sensory or autonomic function. The key talking points on this slide are as follows: Patients with neuropathic pain usually express a variety of distinct sensory symptoms that may coexist in all combinations. The nature of the symptoms depends on the functional system that has been affected. All positive and negative symptoms across all the functional systems should be explored during examination of a patient with suspected neuropathic pain. References Baron R. Clin J Pain. 2000;16:S12-S20. Serra J. Acta Neurol Scand Suppl. 1999;173:7-11 Los cambios sensoriales y el dolor pueden coexistir *También conocido como dolor independiente de los estímulos Baron R. Clin J Pain. 2000;16:S12-S20.

Fisiopatología del dolor neuropático: Resumen
El dolor neuropático es iniciado o causado por una lesión primaria o disfunción en el sistema nervioso Periférico o central en origen El dolor neuropático periférico a menudo puede coexistir con dolor nociceptivo Los mecanismos periféricos y centrales median el dolor neuropático independiente de la etiología Caracterizado por síntomas positivos y negativos Compartidos entre los estados del dolor neuropático The key talking points on this slide are as follows: Neuropathic pain is defined by the IASP as ‘pain initiated or caused by a primary lesion or dysfunction in the nervous system’. It may be peripheral or central in origin. Most neuropathic pain is peripheral in origin and is caused by trauma, metabolic disturbances, infections, toxins, vascular disorders etc. Conditions associated with mixed pain may be prevalent (i.e. co-existence of neuropathic and nociceptive pain). e.g. cancer pain, low back pain, carpal tunnel syndrome Multiple peripheral and central pathophysiologic mechanisms underlie neuropathic pain. These include membrane hyperexcitability with ectopic discharges in both peripheral or central axons, peripheral sensitization, wind-up, central sensitization, denervation supersensitivity and loss of inhibitory controls. Central and peripheral mechanisms mediate pain independent of etiology. Neuropathic pain is characterized by both positive and negative signs and symptoms that may coexist and are shared across neuropathic pain states. Spontaneous and stimulus-evoked pain are examples of positive symptoms; numbness and reduced sensation are examples of negative symptoms. The relationship between mechanisms, symptoms and etiology is varied and relatively poorly understood. Additional key words: pathophysiology

Desafíos en el diagnóstico del dolor neuropático
Sintomatología diversa1 Mecanismos múltiples1 Dificultades en la comunicación y comprensión de los síntomas Los pacientes pueden encontrar difícil articular sus síntomas claramente Los médicos pueden encontrar difícil interpretar parte de la terminología que los pacientes utilizan para describir sus síntomas Respuesta variable al tratamiento2 This slide outlines the key challenges associated with diagnosing neuropathic pain. The key talking points on this slide are as follows: Part of the problem with recognizing neuropathic pain lies with the diversity of the symptomatology of the various pain syndromes and the multiplicity of the mechanisms that underlie them. The relationship between etiology, mechanisms and symptoms is complex; the same symptom in two patients may be caused by different mechanisms. Similarly, one mechanism could be responsible for many symptoms.1 In addition, reaching a diagnosis may be hampered by difficulties in communication between patients and their doctors. Patients may find the symptoms they experience difficult to describe and physicians may not always be able to interpret the terminology patients use to describe their symptoms. Because of the complexity of the relationship between mechanisms and symptoms, patients often respond differently to treatment of exactly the same pain syndrome. For example, two patients with PHN may respond differently to the same treatment. This can confound diagnosis even further.2 References Woolf CJ, Mannion RJ. Lancet. 1999;353: Bonezzi C, Demartini L. Acta Neurol Scand Suppl. 1999;173:25-3 1. Woolf CJ, Mannion RJ. Lancet. 1999;353: 2. Bonezzi C, Demartini L. Acta Neurol Scand Suppl. 1999;173:25-3

Historia del dolor en el dolor neuropático
Identificar los siguiente:1 Áreas de exploración adicional Tipo, distribución y localización del dolor Tipo de quejas e.g. ardor, similar a choque, alfileres y agujas, etc. Con base en un dibujo anatómico Territorio nervioso Extensión extraterritorial Duración de las quejas Intensidad promedio del dolor el último día/semana (0-10) Extensión de la interferencia con la actividad diaria (0-10) Historia medica previa Exposición a toxinas u otro tratamiento con fármacos e.g. taxol, radiación Uso de medicamentos para el dolor Alteración del estado de ánimo y psicológica asociada The assessment of neuropathic pain involves a series of systematic steps that should ideally be consistent between examiners. This slide show an example of how a diagnostic work-up might be performed for a patient with suspected neuropathic pain. The key talking points on this slide are as follows: The pain history should accompany a standard medical examination. The pain history should clarify pain location, distribution, intensity, quality and time course as well as the underlying disease and possibly the nervous system lesion responsible for the pain. In taking a full pain history, physicians should also explore any impact of the pain on sleep, daily functioning and emotional well-being. The possibility of the patient having psychiatric comorbidities such as anxiety and depression should also be explored. Reference Jensen and Baron. Pain. 2003;102:1-8 Additional key words: diagnosis, assessment 1. Jensen and Baron. Pain. 2003;102:1-8

Condiciones de la duración del dolor neuropático
67% de los pacientes tuvieron dolor neuropático por más de 1 año N=600 % de los que respondieron This slide shows results from the European Burden of Illness Survey, which was a cross-sectional, observational, one-time survey of patient self-reported health and well-being, pain experience, medication use and related treatment issues. The survey was conducted in 602 subjects with painful neuropathic conditions recruited by general practitioners and non-pain specialists in 6 European countries (France, Germany, Italy, The Netherlands, Spain and the UK). In total, 600 patients provided responses on the duration of their neuropathic pain. Physicians recruited patients as they presented for a regularly clinic scheduled visit. Patients must have experienced neuropathic pain due to one of 10 study-defined neuropathic pain conditions in the previous 7 days. Patients with low back pain were excluded from the survey to ensure that only those patients with clearly defined neuropathic pain were included. The mean age of the patient population was 63 years, with 50% of participants ≥65 years old. Equal numbers of men and women were recruited. The most frequent neuropathic pain conditions were DPN (23% of participants), PHN (14%), cervical radiculopathy (14%), trigeminal neuralgia (14%) and post traumatic neuropathy (12%). The key talking points on this slide are as follows: This survey confirmed that individuals with neuropathic pain often suffer for long periods of time. Two-thirds of patients involved in the survey (67%) had been suffering from neuropathic pain for more than 1 year. 43% of patients had been suffering from neuropathic pain for more than 3 years. Reference Data on file. Pfizer Inc. European Survey in Painful Neuropathic Disorders Additional key words: diabetes, diabetic, postherpetic 3 a 6 3 a 6 13 a 35 7 a 12 Meses con dolor neuropático Data on file, Pfizer Inc. European Survey in Painful Neuropathic Disorders

Prevalencia/Incidencia del dolor neuropático en diferentes condiciones
20-24% de los diabéticos experimentan DPN1 dolorosa 25-50% de los pacientes >50 años con herpes zoster desarrollan neuralgia postherpética (≥3 meses después de la curación del brote)1 Hasta 20% desarrollan dolor postmastectomía2 Un tercio de los pacientes con cáncer tienen dolor neuropático (solo o con dolor nociceptivo)3 7% de los pacientes con lumbalgia pueden tener dolor neuropático asociado4 The true prevalence of neuropathic pain in the general population is unknown because of a lack of large scale epidemiological studies. Current estimates suggest that up to 2% of the general population may be affected5, but this is likely to be an underestimate. This slide presents prevalence/incidence data from individual studies that have been conducted in different patient populations, including those with diabetes and cancer. The key talking points on this slide are as follows: Neuropathic pain is prevalent among patients with diabetes and following herpes zoster infection (shingles).1 Up to one quarter of patients with diabetes mellitus experience painful DPN; increased age, duration of diabetes, and poorer glycemic control are all thought to increase the risk of painful DPN.1 It has been estimated that around half of all patients (aged >50 years) with herpes zoster will be experiencing PHN at 3 months if they do not receive antiviral therapy.1 Even with antiviral treatment, 25% of these patients will experience PHN at 3 months. Post-mastectomy pain (a distinctive post-surgical neuropathic pain syndrome) may occur in 20% of women who have had a mastectomy.2 Neuropathic pain occurs in one-third of patients with cancer.3 Among patients with low back pain, 7% are estimated to have neuropathic pain (herniated disc or spinal stenosis)4 References Schmader. Clin J Pain. 2002;18:350-4. Stevens et al. Pain. 1995;61:61-8 Davis and Walsh. Am J Hosp Palliat Care. 2004;21(2): Deyo and Weinstein. NEJM 2001;344(5):363 – 370 Chong et al. J Pain Symptom Manage. 2003;25:S4-11 Additional key words: diabetic 1. Schmader. Clin J Pain. 2002;18: Stevens et al. Pain. 1995;61:61-8 3. Davis and Walsh. Am J Hosp Palliat Care. 2004;21(2): 4. Deyo and Weinstein. NEJM 2001;344(5):

Los médicos descubren que el dolor neuropático es más difícil de reconocer en algunas condiciones que en otras Qué tan desafiante es reconocer el dolor neuropático en los pacientes con las siguientes condiciones (n = 1230; incluyendo 35% médicos generales, 9% especialistas en medicina del dolor) No es fácil de reconocer % de médicos This slide describes the results from the Neuropathic Pain Patient Flow Survey, an extensive survey conducted in the UK, France, Germany and Spain, which involved 1230 physicians and 1172 patients with confirmed neuropathic pain (including axial back pain with a neuropathic component). The survey used both qualitative research (in-depth interviews with patients and physicians and focus groups) and quantitative research (interviews and case reviews with pain clinicians and patient questionnaires) to assess issues relating to the management of neuropathic pain. Physicians from different disciplines were asked to rate how challenging they found recognizing neuropathic pain in patients with particular conditions. The key talking points on this slide are as follows: As part of the survey, 1230 physicians from a variety of disciplines were asked how challenging it was to recognize neuropathic pain in different disease states on a 5-point scale: extremely challenging, somewhat challenging, neutral, somewhat easy, extremely easy. The slide shows the percentages of all physicians surveyed who did not find pain easy or somewhat easy to recognize. Among the 1230 physician respondents, the breakdown of specialty was as follows: GPs 35%, neurologists 16%, oncologists 12%, pain medicine specialists (PMS) 9%, HIV specialists 8%, rheumatologists 8%, endocrinologist 7%, orthopaedic/trauma specialists 5%. Mixed neuropathic pain states were generally harder to recognize than “pure” neuropathic pain states. However, even some pain states that might be considered to be “pure” neuropathic pain (e.g. DPN) or have an obvious and substantial neuropathic pain component (Cancer, HIV) were not easily recognized by over 50% of physicians. These data indicate that neuropathic pain may be under-recognized by physicians. Abbreviations: PHN – postherpetic neuralgia, CTS- carpal tunnel syndrome, TGN - trigeminal neuralgia, DPN – diabetic peripheral neuropathy, SCI- spinal cord injury, MS-multiple sclerosis, RSD- reflex sympathetic dystrophy (a complex regional pain syndrome) Reference Data on file, Pfizer Inc. Neuropathic Pain patient Flow Survey Additional key words: diagnosis, recognition Cáncer Neuralgia del trigémino Lumbalgia superior Lumbalgia inferior Lumbalgia inferior Cáncer Esclerosis múltiple VIH/SIDA Distrofia simpática refleja Virus Humuno Def H/SIDA Neuralgia postherpética Síndrome tunel carbal Neuropatía diabética periférica Lesión en médula espinal Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

Necesidades sin satisfacer en el manejo del dolor neuropático
El diagnóstico es a menudo desafiante Los mecanismos implicados son complejos Variabilidad de los síntomas a través de los pacientes y a través de los estados del dolor Reconocimiento y manejo de condiciones comórbidas pueden ser pasadas por alto La selección de opciones de tratamiento puede ser subóptima This slide describes some of the unmet needs in the management of neuropathic pain. The author reviewed the literature and identified the main areas where improvements are required to enhance the management of neuropathic pain. key talking points on this slide are as follows: The diagnosis of neuropathic pain can be challenging. (this is also reflected in other slides within this section based on data not reviewed by the author). Some of the reasons for this are that the mechanisms that underpin neuropathic pain are complex and that symptoms vary among patients with the same underlying etiology and across pain states of different etiologies, although there are many commonly reported symptoms. Comorbid conditions, such as anxiety and depression are common and may further contribute to functional impairment and disability among patients with neuropathic pain. They are often overlooked and need to be taken into account to achieve optimal management of patients with neuropathic pain. The selection from available treatments may be sub-optimal. Inappropriate treatments are often used and this may, in part, be due to lack of understanding of which treatments are most appropriate for neuropathic pain, and which analgesics confer little benefit. Reference Harden and Cohen. J Pain Symptom Manage. 2003;25 (5S)S12-S17 Harden and Cohen. J Pain Symptom Manage. 2003;25 (5S)S12-S17

Las comorbilidades se agregan al desafío médico en el dolor neuropático

Interrelación entre el dolor, sueño y ansiedad/depresión
Deterioro Funcional Patients who suffer from chronic pain experience difficulties initiating and maintaining sleep and are often depressed and anxious. The inter-relationship between these three factors, as shown on this slide, is complex, but must be considered carefully if treatment for neuropathic pain is to be satisfactory. The key talking points on this slide are as follows: Although most pain disorders begin with injury or disease, their course and outcome are affected by emotional, behavioral and social factors. An individual’s emotional reaction to, and capacity to cope with, the fluctuating course of neuropathic pain disorders and their complications such as physical impairment, disability, and loss of role functioning will also affect outcome. Chronic pain significantly interferes with sleep, with most studies showing a positive correlation between pain intensity and degree of sleep disturbance. Many chronic pain patients have signs and symptoms of depression and anxiety; sleep deprivation can lead to anxiety, and depression can be both the cause and result of sleep deprivation. Chronic pain, sleep disturbances, and depression/anxiety must be addressed if patients are to be restored to optimal functionality. Physicians must evaluate all aspects of pain, sleep and mood in patients with chronic pain. Management and treatment should address both the pain and the comorbidities, to improve daily functioning, and enhance quality of life. Reference Nicholson and Verma. Pain Med. 2004;5(suppl. 1):S9-S27 Additional key words: mood Ansiedad y depresión Alteraciones en el sueño Nicholson and Verma. Pain Med. 2004;5 (suppl. 1):S9-S27

Pacientes con dolor neuropático periférico experimentan síntomas comórbidos significativos
Dificultad para dormir Falta de energía Somnolencia Dificultades en la concentración Depresión Ansiedad This study was undertaken to assess the health-related quality of life and burden of illness due to pain and its treatment in 126 patients with neuropathic pain due to a peripheral nerve or root lesion. Patients were recruited from 2 multidisciplinary pain clinics in Sweden. Patients were asked to rate the extent to which they were bothered by 25 pain-related symptoms and/or side-effects of drug treatment during the previous week (rated as 1=no discomfort to 7=very severe discomfort). This slide shows the proportions of patients who rated their discomfort as 4 (moderate) to 7 (very severe). Data on 7 of the 10 most frequently reported comorbid symptoms are shown on the slide. Overall, 88% of patients reported some degree of discomfort associated with their pain or its treatment. The key talking points on this slide are as follows: Difficulty sleeping was the most bothersome symptom and was moderate to very severe in 60% of patients. A lack of energy, drowsiness, and difficulty in concentrating, were also troubling for many individuals. Moderate to very severe levels of depression were reported by 35% (1 in 3 patients), and anxiety by 27% (1 in 4 patients) These data indicate that sleep disturbance, anxiety and depression and related symptoms are prevalent among patients with peripheral neuropathic pain. Reference Meyer-Rosberg et al. Eur J Pain. 2001;5(4): Additional key words: mood Pobre apetito % de pacientes con molestia moderada a muy severa (n = 126) Meyer-Rosberg et al. Eur J Pain. 2001;5:

La ansiedad y la depresión son frecuentes en el dolor crónico
283 pacientes evaluados en centros de dolor1 63% con síntomas de ansiedad significativos (DSM-III) 56% con síntomas depresivos significativos (DSM-III) Depresión 71 de los pacientes con lumbalgia crónica2 44% con depresión mayor, 11% con menor (SADS-L) This slide reviews the results of 2 studies that have investigated the prevalence of anxiety and depression in patients with chronic pain (of different aetiologies) using validated psychiatric assessment instruments. In the study by Fishbain et al,1 283 chronic pain patients who were admitted consecutively to a pain center were evaluated using DSM-III criteria. In the study by Krishnan et al,2 71 patients with chronic low back pain were evaluated using the SADS-L criteria. The key talking points on this slide are as follows: Both anxiety and depression are common comorbidities in patients with chronic pain. In these studies, significant depressive symptoms were apparent in over 50% of individuals with chronic pain. Significant anxiety symptoms were found in over 60% of patients with chronic pain.1 Anxiety and depression in these patients may stem from the stressful negative consequences of living with pain (e.g. interference with work, relationships, and hobbies), as well as knowing that they have a painful condition with no particular treatable cause and no apparent way to obtain relief.3 Anxiety and depression may also result from sleep deprivation caused by pain-related sleep interference.3 Abbreviations: DSM-III: Diagnostic and Statistical Manual of Mental Disorders III; SADS-L: Schedule for affective disorders and schizophrenia – Lifetime version References Fishbain et al. Pain. 1986;26(2): Krishnan et al. Pain. 1985;22(3): Nicholson and Verma. Pain Med. 2004;5(suppl. 1):S9-S27 Additional key words: mood 1.Fishbain DA et al. Pain 1986;26: 2.Krishnan KR et al. Pain 1985;22:

Data on file, Pfizer Inc. Elderly PHN Survey
Los pacientes con neuralgia postherpética tienen un deterioro significativo en el sueño, estado de ánimo y actividad relacionado con el dolor Magnitud del deterioro en el inventario modificado breve del dolor (n=385) Moderado Moderado Severo % de los que respondieron This slide shows results from a population-based survey of 385 elderly (≥65 years of age) individuals with pain due to PHN (≥3 months). Subjects were recruited via advertisements in 24 newspapers in the USA. Respondents completed a 32-item questionnaire that addressed pain intensity, pain interference with daily activities, and health-related quality of life. Respondents were also asked about their use of prescription (Rx) and over-the-counter (OTC) medications for shingles pain, and satisfaction with therapy. Sixty-one percent of participants were 75 years of age or older; 59% were women. The mean duration of PHN was 3.3 years. The key talking points on this slide are as follows: The 7-item modified Brief Pain Inventory (mBPI) used in this survey required patients to rate the extent to which pain interfered with their daily activities, mood, relations with other people, sleep and enjoyment of life during the previous week. Response categories ranged from 0 (did not interfere) to 10 (completely interfered). Mild/no interference = 0-3, moderate interference = 4-6 , severe interference = 7-10. Almost all patients reported that their pain interfered with their sleep, mood and general activities to some extent. The extent of impairment was similar across these 3 domains, and although impairments across these domains might be related, the data have not been analyzed to investigate this. Approximately 25% (1 in 4 patients) reported moderate interference from pain in each of the 3 domains. Approximately 15% (1 in 6 patients) reported severe interference from pain in each of the 3 domains. These data demonstrate that 40% of patients with PHN have moderate or severe impairment in sleep, mood and general activities. Reference Data on file, Pfizer Inc, New York, NY, USA. Elderly PHN Survey. Additional key words: postherpetic Sueño Estado de ánimo Actividades generales Moderado: 4-6; Severo: 7-10 Data on file, Pfizer Inc. Elderly PHN Survey

Condiciones médicas crónicas comórbidas
Condiciones médicas crónicas comórbidas* entre los pacientes con trastornos neuropáticos dolorosos Convulsiones Convulsiones Otros de salud mental Insuficiencia renal Depresión Insuficiencia cardiaca congestiva Enfermedad pulmonar obstructiva crónica Enfermedad cardiaca coronaria This slide presents data from a retrospective chart review of 55,686 patients (≥ 18 years old) with painful neuropathic disorders in a USA-based managed care organization compared with age- and gender-matched controls (n=55,686 in each group). The prevalence of comorbid medical conditions among patients with neuropathic pain was evaluated. This was based on healthcare claims for the comorbid conditions listed i.e. patients diagnosed with the condition and receiving some form of treatment. key talking points on this slide are as follows: In this database, approximately two-thirds of patients were at least 50 years old, and almost one-third were at least 65 years old. This probably reflects the fact that neuropathic pain and some of the conditions that may lead to it, increase with increasing age. Patients with neuropathic pain often have comorbid medical disorders. They may be medically ill either because of the same condition that is related to their neuropathic pain (e.g. diabetes), comorbidities that may develop in association with their neuropathic pain (e.g. depression) or as a function of their age and environmental factors. Therefore, when managing and treating patients with neuropathic pain, it is important to be aware of the fact that they may have poor health in other domains and may be on medication for related or unrelated illnesses. Reference Berger et al. J Pain. 2004;5(3): Diabetes % de pacientes (n = ) *Con base en los reclamos del cuidado de la salud Berger et al J Pain. 2004;5(3):

El dolor neuropático está asociado con un deterioro significativo en la calidad de vida y funcionamiento

Los pacientes con dolor neuropático periférico tienen una calidad de vida significativamente deteriorada en comparación con la población general Población general sueca (n = 8930) Población de estudio (n = 126) Puntuación media del SF-36 This study investigated pain, employment status and quality of life in a survey of 126 patients with neuropathic pain (PHN, or lesion of peripheral, spinal or root nerve) from 2 Swedish Multidisciplinary Pain Centres. Patients rated quality of life on the Short-Form 36 (SF-36) questionnaire. The author compared values from patients with reference values for the Swedish General Population The key talking points on this slide are as follows: Patients with peripheral neuropathic pain have significantly impaired quality of life compared with the general population. Decrements in all domains can be seen on the slide, indicating that peripheral neuropathic pain is associated with impaired functional status and well-being across multiple domains, not just pain and physical function. Reference Meyer-Rosenberg et al. Eur J Pain. 2001;5(4): Función física Dolor corporal Salud general Vitalidad Salud mental Papel físico Función social Papel emocional Meyer-Rosenberg et al. Eur J Pain. 2001;5:

% de pacientes con interferencia substancial en la función (n = 105)
Pacientes con neuropatía diabética periférica tienen un deterioro funcional substancial a través de múltiples dominios Deterioro en la puntuación modificada del inventario breve del dolor 5 Social Recreación Cuidado propio Disfrute Sueño Relaciones Trabajo normal Movilidad In this survey of 105 patients with painful diabetic peripheral neuropathy (DPN ) patients were asked to complete the 10-item modified Brief Pain Inventory (mBPI), which required patients to rate the extent to which pain interfered with their daily activities, mood, normal work, relations with other people, sleep, enjoyment of life, self care, recreational and social activities during the previous week. Response categories ranged from 0 (did not interfere) to 10 (completely interfered). A score of 5 was considered an indication of substantial interference with activities because of pain. This slide reflects domains for which interference in function was substantial i.e. score 5. In this survey, the average age of respondents was 63 years; first onset of neuropathic pain was at the mean age of 57 years. The key talking points on this slide are as follows: A substantial proportion of patients reported that pain interfered with function in each of the 10 domains assessed (35-58%). Over half the patients reported substantial impairment in social and recreational activities, enjoyment of life, mobility and being able to work normally. Almost 60% reported that pain substantially interfered with sleep. Over 40% reported that pain substantially affected their mood. The results of this survey demonstrate that DPN has a definite and measurable negative impact on patient quality of life. Reference Galer et al. Diabetes Res Clin Pract. 2000;47(2): Estado de ánimo General % de pacientes con interferencia substancial en la función (n = 105) Galer et al. Diabetes Res Clin Prac 2000;47:

Comorbilidades en el dolor neuropático
Las condiciones comórbidas significativas están asociadas con el dolor neuropático Alteración en el sueño Trastornos del estado de ánimo Ansiedad y depresión En pacientes con dolor neuropático se reporta una disminución en la calidad de vida y un deterioro funcional This slide summarizes the previous slides that have addressed comorbid conditions and impairment of quality of life and function in patients with neuropathic pain. key talking points on this slide are as follows: Neuropathic pain is associated with significant comorbid conditions. Among these are sleep disturbance and signs and symptoms of anxiety and depression (see previous slide also). Patients with neuropathic pain have reduced quality of life, across multiple domains, and significant impairment of function in everyday activities. In the treatment of the “whole” patient with neuropathic pain, it is important to be mindful of those aspects, beyond pain itself, that may impact on achieving a good outcome.

Médicos generales: Papel crucial en el diagnóstico y tratamiento del dolor neuropático
Some of the slides in this sub-section are based on an extensive survey of physicians and patients in Europe (Neuropathic Pain Patient Flow Survey). The Neuropathic Pain Patient Flow Survey was an extensive survey conducted in the UK, France, Germany and Spain, which involved 1230 physicians and 1172 patients with confirmed neuropathic pain (including axial back pain with a neuropathic component). Among the 1230 physician respondents, the breakdown of specialty was as follows: general practitioners (GPs) 35%, neurologists 16%, oncologists 12%, pain medicine specialists (PMS) 9%, HIV specialists 8%, rheumatologists 8%, endocrinologist 7%, orthopaedic/trauma specialists 5%. The survey used both qualitative research (in-depth interviews with patients and physicians and focus groups) and quantitative research (interviews and case reviews with pain clinicians and patient questionnaires) to assess issues relating to the management of neuropathic pain. The slides in this subsection address the role general practitioners (GPs) play in the management and treatment of neuropathic pain, and how well equipped they feel to do so.

Los médicos generales juegan un papel crucial en el manejo continuo del dolor neuropático
¿Qué tipo de médico ve usted primero, qué tipo de médico es más responsable para tratar el dolor que usted le ha descrito? Otro Especialista en medicina del dolor Neurocirujano Cirujano Reumatólogo % de pacientes Especialista en cuidado paleativo Neurólogo The slide describes the results from the Neuropathic Pain Patient Flow Survey, an extensive survey of physicians and patients in Europe (Neuropathic Pain Patient Flow Survey). The Neuropathic Pain Patient Flow Survey was an extensive survey conducted in the UK, France, Germany and Spain, which involved 1230 physicians and 1172 patients with confirmed neuropathic pain (including axial back pain with a neuropathic component). The survey used both qualitative research (in-depth interviews with patients and physicians and focus groups) and quantitative research (interviews and case reviews with pain clinicians and patient questionnaires) to assess issues relating to the management of neuropathic pain. Patients with neuropathic pain (n=1056) responded when asked about what type of doctor they first saw for their pain, and what type of doctor is most responsible for treating their pain now. In the UK and Spain patients must go to a general practitioner (GP) first if they are not currently under the care of a specialist; in France and Germany they may seek specialist treatment without seeing a GP. The key talking points on this slide are as follows: Based on patient reports, the median number of physicians consulted for the treatment of pain was 2 and the median number of visits to a physician for the management of pain was 3 in the last year. Three-quarters (75%) of patients first consulted their GP for their pain. Over half (54%) were currently managed by their GP. Only 18% of patients were currently managed mainly by a neurologist and only 1% by a pain medicine specialist. These data indicate that GPs play a pivotal role in diagnosing and managing neuropathic pain. Reference Data on file, Pfizer Inc. Neuropathic Pain Patient Flow Survey. Cirujano ortopédico Médico general Median # MDs seen = 2 Visits in last year = 3 Mediana # Primer doctor visto Doctor actual Médicos vistos = 2 (n=1056) (n=1056) Visitas el año pasado = 3 Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

Los médicos generales juegan un papel crucial en el manejo continuo del dolor neuropático
Porcentaje de todos los pacientes encuestados en total (n = 1056) 75% % de pacientes con dolor neuropático 54% 46% 29% 25% The slide presents similar data to the previous slide, but demonstrates the overall flow of patients from first seeing their GP to ultimately being managed by their GP or a specialist. The results from the Neuropathic Pain Patient Flow Survey, an extensive survey of physicians and patients in Europe (Neuropathic Pain Patient Flow Survey). The Neuropathic Pain Patient Flow Survey was an extensive survey conducted in the UK, France, Germany and Spain, which involved 1230 physicians and 1172 patients with confirmed neuropathic pain (including axial back pain with a neuropathic component). The survey used both qualitative research (in-depth interviews with patients and physicians and focus groups) and quantitative research (interviews and case reviews with pain clinicians and patient questionnaires) to assess issues relating to the management of neuropathic pain. Patients with neuropathic pain (n=1056) responded when asked about what type of doctor they first saw for their pain, and what type of doctor is most responsible for treating their pain now. In the UK and Spain patients must go to a general practitioner (GP) first if they are not currently under the care of a specialist; in France and Germany they may seek specialist treatment without seeing a GP. The key talking points on this slide are as follows: It should be noted that the percentages expressed on the slide represent the % of entire patient population surveyed (they are not subsets of the 75% of GPs who were first consulted for pain, but the % of the entire patient population). Three-quarters (75%) of patients first consulted their GP for their pain. GPs referred 46% of all patients to a specialist (not necessarily a pain specialist). GPs reported that 25% of all patients were referred from the specialist back to the GP for the management of their pain. 29% of all patients were never referred to a medical specialist of any description and therefore had been managed entirely by their GP. Over half (54%) were currently managed by their GP. Only 18% of patients were currently managed mainly by a neurologist and only 1% by a pain medicine specialist. These data indicate that GPs play a pivotal role in diagnosing and managing neuropathic pain. Reference Data on file, Pfizer Inc. Neuropathic Pain Patient Flow Survey. Referido nuevamente a médico general por especialista Médico general primer doctor visto Médico general refiere a especialista Nunca Referido a especialista Médico general actualmente maneja el dolor Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

Reconocer de la mayoría del dolor neuropático es fácil para mí
Los médicos generales son los que más se enfrentan al reto de reconocer el dolor neuropático Reconocer de la mayoría del dolor neuropático es fácil para mí Algo de acuerdo Firmemente de acuerdo % de médicos The slide describes the results from the Neuropathic Pain Patient Flow Survey, an extensive survey of physicians and patients in Europe (Neuropathic Pain Patient Flow Survey). The Neuropathic Pain Patient Flow Survey was an extensive survey conducted in the UK, France, Germany and Spain, which involved 1230 physicians and 1172 patients with confirmed neuropathic pain (including axial back pain with a neuropathic component). The survey used both qualitative research (in-depth interviews with patients and physicians and focus groups) and quantitative research (interviews and case reviews with pain clinicians and patient questionnaires) to assess issues relating to the management of neuropathic pain. Among the physicians from a variety of disciplines, 428 (35%) were general practitioners (GPs). All physicians were asked to rate the extent to which they agree with the statement “Recognizing most neuropathic pain is easy for me” on a 5-point scale strongly disagree, somewhat disagree, neutral, somewhat agree, strongly agree. The key talking points on this slide are as follows: GPs were most challenged in the recognition of neuropathic pain. Pain medicine specialists (PMS) were, as expected, least challenged. The extent to which other specialties were challenged might reflect the exposure to patients with neuropathic pain, or their perceived importance of neuropathic pain within their specialty. Abbreviations GP- general practitioner, Onc-oncologist, Rheum-rheumatologist, HIV- HIV medicine specialist, Neuro- neurologist, Endo-endocrinologist, PMS – pain medicine specialist. Reference Data on file, Pfizer Inc. Neuropathic Pain Patient Flow Survey Additional key words: diagnosis Médicos generales (n = 428) Oncólogos (n = 144) Reumatólogos (n = 99) VIH (n = 103) Neurólogo (n = 200) Endocrin. (n = 87) Especialistas En medicina del dolor (n = 108) Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

% de médicos (médicos generales)
Los médicos generales descubren que el dolor neuropático es más difícil de reconocer en algunas condiciones que en otras ¿Qué tan desafiante es reconocer el dolor neuropático en los pacientes con las siguientes condiciones? (n = 428 médicos generales) No es fácil reconocer % de médicos (médicos generales) The slide describes the results from the Neuropathic Pain Patient Flow Survey, an extensive survey of physicians and patients in Europe (Neuropathic Pain Patient Flow Survey). The Neuropathic Pain Patient Flow Survey was an extensive survey conducted in the UK, France, Germany and Spain, which involved 1230 physicians and 1172 patients with confirmed neuropathic pain (including axial back pain with a neuropathic component). The survey used both qualitative research (in-depth interviews with patients and physicians and focus groups) and quantitative research (interviews and case reviews with pain clinicians and patient questionnaires) to assess issues relating to the management of neuropathic pain. Physicians from different disciplines were asked to rate how challenging they found recognizing neuropathic pain in patients with particular conditions. The key talking points on this slide are as follows: As part of the survey, 428 GPs were asked how challenging it was to recognize neuropathic pain in different disease states on a 5-point scale: extremely challenging, somewhat challenging, neutral, somewhat easy, extremely easy. The slide shows the percentages of all GPs surveyed who did not find pain easy or somewhat easy to recognize. Mixed neuropathic pain states were generally harder to recognize than “pure” neuropathic pain states. However, even some pain states that might be considered to be “pure” neuropathic pain (e.g. DPN) or have an obvious and substantial neuropathic pain component (Cancer, HIV) were not easily recognized by over 50% of GPs. Abbreviations: PHN – postherpetic neuralgia, CTS- carpal tunnel syndrome, TGN - trigeminal neuralgia, DPN – diabetic peripheral neuropathy, SCI- spinal cord injury, MS-multiple sclerosis, RSD- reflex sympathetic dystrophy (a complex regional pain syndrome) Reference Data on file, Pfizer Inc. Neuropathic Pain patient Flow Survey Additional key words: diagnosis Neuralgia postherpética Síndrome del túnel carpal Neuralgia del trigémino Lumbalgia baja Neuropatía diabética periférica Lesión de la médula espinal Lumbalgia superior Cáncer VIH/SIDA Distrofia simpática refleja Esclerosis múltiple Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

Los médicos generales son cruciales en el manejo del dolor neuropático
Los médicos generales son cruciales en el manejo y tratamiento del dolor neuropático1 La mayoría de los pacientes primero ven a sus médicos generales Aproximadamente 50% de los pacientes son manejados por médicos generales A pesar de la alta prevalencia del dolor crónico visto por los médicos generales, únicamente una pequeña proporción de todos los pacientes que son vistos por médicos generales tienen dolor neuropático Los médicos generales se enfrentan más al desafío de reconocer el dolor neuropático Es necesario mejorar la educación sobre el dolor This slide describes the results from the Neuropathic Pain Patient Flow Survey, an extensive survey conducted in the UK, France, Germany and Spain, which involved 1230 physicians and 1172 patients with confirmed neuropathic pain (including axial back pain with a neuropathic component). The survey used both qualitative research (in-depth interviews with patients and physicians and focus groups) and quantitative research (interviews and case reviews with pain clinicians and patient questionnaires) to assess issues relating to the management of neuropathic pain. As part of the survey, 1056 patients with neuropathic pain provided responses about what type of doctor they first visited for their pain and what type of doctor was responsible for managing their pain at the time of the survey. 428 general practitioners (GPs) were asked how easy they found it to recognize neuropathic pain. The key talking points on this slide are as follows: GPs play a key role in the diagnosis and management of neuropathic pain. Three-quarters (75%) of patients first consulted their GP for their pain. Over half (54%) were being managed by their GP at the time of the survey. Despite the high prevalence of chronic pain among patients seen by the GPs surveyed (24% of all patients) only one-quarter of chronic pain patients were reported by GPs to have neuropathic pain. Thus, in this sample neuropathic pain patients only represented 6% of all patients seen by the GPs surveyed. GPs admit to finding it difficult to recognize neuropathic pain. There is a clear need for enhanced education of GPs and other non-pain specialists to improve the recognition and diagnosis of neuropathic pain. References 1. Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey 2. Harden and Cohen. J Pain Symptom Manage. 2003;25 (5S)S12-S17 1. Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

Los pacientes buscan tratamiento, pero continúan experimentando dolor

La mayoría de los pacientes con dolor neuropático han hablado con su médico sobre su dolor
Han visto a un médico No han visto a un médico Cáncer (n = 47) Dolor central (n = 92) Virus Inmunod. Humana (n = 37) Compresión (n = 28) Buscan cuidado Reino Unido = 83% Francia = 93% Alemania = 88% España = 93% Focal (n = 53) Dolor radicular espalda (n = 181) Neuropatía diabética periférica (n = 38) Mecanismo desconocida/múltiple (n = 147) Dolor axial espalda (n = 534) This slide describes the results from the Neuropathic Pain Patient Flow Survey, an extensive survey conducted in the UK, France, Germany and Spain, which involved 1230 physicians and 1172 patients with confirmed neuropathic pain (including axial back pain with a neuropathic component). The survey used both qualitative research (in-depth interviews with patients and physicians and focus groups) and quantitative research (interviews and case reviews with pain clinicians and patient questionnaires) to assess issues relating to the management of neuropathic pain. As part of the survey, 1056 patients with neuropathic pain were asked if they had ever talked to a doctor about the pain they described. The key talking points on this slide are as follows: Most patients had talked to their doctor about their neuropathic pain, indicating that they were seeking help. Reference Data on file, Pfizer Inc. Neuropathic Pain Patient Flow Survey Total (n = 1172) 11% % de pacientes ¿Ha conversado usted con su médico sobre el dolor que describió? Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

Experiencia del dolor en pacientes con dolor neuropático en una encuesta en el Reino Unido
El peor dolor en las últimas 24 horas Índice de severidad del dolor Leve Leve Severo 13% 21% 25% Severo 51% 37% 54% Moderado Moderado This slide shows results from the European Burden of Illness Survey, which was a cross sectional, observational, one-time survey of patient self-reported health and well-being, pain experience, medication use and related treatment issues. The survey was conducted in 602 subjects with painful neuropathic conditions recruited by general practitioners and non-pain specialists in 6 European countries (France, Germany, Italy, The Netherlands, Spain and the UK). Physicians recruited patients as they presented for a regularly clinic scheduled visit. Patients must have experienced neuropathic pain due to one of 10 study-defined neuropathic pain conditions in the previous 7 days. Patients with low back pain were excluded from the survey to ensure that only those patients with clearly defined pain were included. The patient questionnaire included the Brief Pain Inventory (BPI) The mean age of the patient population was 63 years, with 50% of participants ≥65 years old. Equal numbers of men and women were recruited. The most frequent neuropathic pain conditions were DPN (23% of participants), PHN (14%), cervical radiculopathy (14%), trigeminal neuralgia (14%) and post traumatic neuropathy (12%). The key talking points on this slide are as follows: Pain severity was determined in this survey using 4 items from the BPI, in which patients graded their pain severity on an 11-point numeric rating scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). Pain was assessed at the time of completing the questionnaire and also at its worst, least, and average over the previous 24 hours. 88% of patients reported that their worst pain in the past 24 hours was moderate or severe. The Pain Severity Index was calculated using the patient’s average of the 4 severity ratings. Scores of 0-3 were considered to represent mild or no pain, scores of 4-6 to represent moderate pain, and scores of 7-10 to represent severe pain. 79% of patients in this survey reported moderate or severe Pain Severity Index scores. Reference Data on file. Pfizer Inc. European Survey in Painful Neuropathic Disorders Additional key words: diabetes, diabetic, postherpetic 88% de los pacientes reportaron su peor dolor como moderado o severo 77% de los pacientes reportaron un índice de severidad del dolor de moderado o severo N = 602; 93% con medicamentos Rx para el dolor N=602; 93% on Rx medication for pain Leve/ninguno: 0-3; Moderado: 4-6; Severo: 7-10 Data on file, Pfizer Inc. European Survey in Painful Neuropathic Disorders

El dolor neuropático es tratado subóptimamente

Tratamientos actuales: Puntos de vista de los expertos
“Un número relativamente grande de pacientes con dolor neuropático fracasan en descubrir el alivio adecuado con las prácticas existentes debido al efecto límite de los medicamentos disponibles; estos pacientes a menudo desarrollan una comorbilidad significativa con un impacto considerable sobre su calidad de vida” Smith y Sang. Eur J Pain.2002:6(suppl B):13-18 “No podemos proveer un tratamiento adecuado para un amplio número de pacientes con dolor neuropático establecido” Taylor BK. Pain and Headache Rep. 2001;5: This slide presents quotations made by experts in the published literature. key talking points on this slide are as follows: In reviewing available evidence, experts concede that many patients fail to achieve satisfactory relief of their neuropathic pain, with available treatments. References Smith and Sang. Eur J Pain.2002:6(suppl B):13-18 Taylor BK. Curr Pain and Headache Rep. 2001;5:

medicamentos de prescripción entre los pacientes tratados por dolor neuropático
Los medicamentos con eficacia establecida representan una pequeña proporción de Rx Todos los otros 2% Anticonvulsivantes 13% Anestésicos locales 6% Estabilizadores estado de ánimo/ antidepresivos 4% Tranquilizantes 9% Opiáceos 4% This slide shows the range of medications prescribed for the treatment of neuropathic pain, according to worldwide prescription data collated by IMS Health Inc., a provider of audited prescription data to the pharmaceutical industry.1 The slide represents data compiled during October-December 2003 in which 143 million prescriptions were written worldwide for neuropathic pain diagnosis codes. The key talking points on this slide are as follows: The wide variety of different types of medication prescribed for neuropathic pain reflects the fact that there is currently little consensus on the optimal pharmacological treatment of neuropathic pain, and that practices vary greatly worldwide.2 Non-steroidal anti-inflammatory drugs (NSAIDs) and non-narcotic analgesics are the most commonly prescribed medications for neuropathic pain. Unfortunately, these primary analgesic therapies used for neuropathic pain are frequently ineffective.2 The high proportion of NSAID prescriptions in this database probably reflects the traditional approach to the treatment of all chronic pain, even though there is little evidence to support the use of NSAIDs in the treatment of neuropathic pain. The treatment of neuropathic pain is largely empirical, often relying on data from small, inadequately designed clinical trials or anecdotal evidence.2 Antidepressants and antiepileptic drugs (AEDs) have some of the best evidence to support their use in the treatment of neuropathic pain.2 The data on the slide suggest, however, that only a relatively small proportion of patients are prescribed these treatments. References 1. IMS global Rx data 4Q 2003 2. Chong et al. J Pain Symptom Manage. 2003;25:S4-11. Additional key words: TCA analgésicos no narcóticos 21% AINES (incl. COX-II) 41% Información mundial sobre Rx del IMS en el 4Q del 2003 (n = 143 millones de Rx)

Carga económica del dolor neuropático
Sociedad Ausentismo Disminución en la productividad laboral Proveedores del cuidado de la salud Costos de los pacientes internados Costos de los pacientes ambulatorios Costos del medicamento Uso subóptimo de recursos Pacientes Costo del medicamento Costo del cuidado Pérdida de ganancias Encargados de cuidado This slide highlights the many factors that contribute to the economic burden of neuropathic pain, which falls on patients and their caregivers and on society as a whole. The key talking points on this slide are as follows: In economic terms, the patient may be required to contribute to the cost of medications and medical/nursing care, whilst often having to cope with loss of earnings.1 To care for patients with severe neuropathic pain, caregivers may have to reduce or give up their paid work. They too may be responsible for the cost of treatment. Neuropathic pain represents a significant cost to society in terms of absenteeism and loss of productivity at work. In the European Survey, 80% of respondents who were employed reported some degree of working productivity loss; over 20% of respondents reported that their productivity was reduced most or all of the time (see later slide).2 Healthcare services shoulder much of the economic burden associated with neuropathic pain.3 Improving the treatment and management of neuropathic pain is essential to minimize the burden of the condition. References Meyer-Rosberg et al. Eur J Pain. 2001;5: Data on file. Pfizer Inc. European Survey in Painful Neuropathic Disorders 3. Berger et al. J Pain. 2004;5:

Dolor neuropático: el desafío Resumen
La prevalencia neuropática puede ser reportada incorrectamente El diagnóstico puede ser desafiante para los médicos Los médicos generales son los que más se enfrentan al desafío, incluso son cruciales en el manejo del dolor neuropático Las condiciones comórbidas son prevalentes Signos y síntomas de ansiedad, depresión, alteración en el sueño El dolor neuropático está asociado con un deterioro funcional significativo y en la calidad de vida El tratamiento actual es subóptimo Tratamientos basados en evidencias (e.g. medicamentos antiepilépticos, antidep. tricícl.) no siempre prescritos Algunos pacientes no responden a medicamentos antiepilépticos ni antidep. tricícl. This slide summarizes the information and data presented in slides and notes within this section. The management and treatment of neuropathic pain is challenging for a variety of reasons: The prevalence of neuropathic pain reported in the literature is 1-2%. However, the extensive European patient Flow Survey suggests that the prevalence is in the order of 7% when axial back pain is included. Thus, the prevalence of neuropathic pain in the general population may be under-reported in the literature. Diagnosis neuropathic pain can be challenging to physicians. GPs appear to have most difficulty, yet most patients first consult their GP about their pain and approximately half are managed and treated by their GP. This indicates that enhanced education is needed among non-pain specialists to improve diagnosis. Comorbid conditions, such as signs and symptoms of anxiety, depression and sleep disturbance are prevalent. These conditions may often be overlooked. Treatment of comorbid conditions is important of functional and well-being is to be maximized. Patients with neuropathic pain have significant impairment of quality of life and function. If pain management was more effective, outcome might be improved. Current treatment is sub-optimal. This is due to the fact that even the available evidence-based therapies such as AEDs and TCAs appear under-prescribed and even when they are prescribed they are not effective and well tolerated in some patients. The development of new effective, well tolerated medications for neuropathic pain should also result in improved outcome for patients.

Eficacia de Pregabalina en el dolor neuropático periférico: Contenido
Revisión del programa de desarrollo, evaluaciones y criterios de selección de los pacientes Resultados combinados de los estudios de neuropatía diabética periférica y neuralgia postherpética Resultados de los estudios clave de neuralgia postherpética Resultados de los estudios clave de neuropatía diabética periférica Resultados del estudio clave de dosis flexible de neuropatía diabética periférica/neuralgia postherpética Resultados a largo plazo de los estudios de extensión de diseño abierto Conclusiones

Eficacia de Pregabalina en el dolor neuropático periférico

Dosis de pregabalina (mg/día)
Tasas de los que respondieron (50% de reducción en el dolor)* entre 10 ensayos clínicos de dolor neuropático periférico ***P vs. placebo *** 47% *** 34% % de pacientes *** 26% 19% This slide shows combined results from 10 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with neuropathic pain associated with DPN or PHN (studies 014, 029, 040, 131, 149, 030, 045, 127, 196, 155; 5-13 weeks duration). The results do not include LYRICA (pregabalin) 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which is included in the analysis, and one flexible-dose LYRICA mg/day arm). Patients were randomized to receive placebo or LYRICA 150, 300, or 600 mg/day. As LYRICA is renally excreted and dosage adjustment is required in renal impairment, in 3 studies, patients with low creatinine clearance (CLcr) (>30 and 60 mL/min) and randomized to the 600 mg/day group received a maximum dose of 300 mg/day, but were analyzed with the 600 mg/day group. In the remaining 7 studies, patients who had a creatinine clearance 60 mL/min were excluded. The primary efficacy variable was the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. A response was defined as having a 30% or 50% reduction in pain score from baseline to end point. The key talking points for this slide are as follows: The 50% responder rates are presented on this slide. A 30% reduction in the pain score has previously been shown to be clinically important (Farrar et al. 2001); a 50% reduction is accepted to be clinically significant and is often used to compare treatment responses for different agents across clinical trials. The 50% responder rate was significantly higher with all three LYRICA doses than placebo. Nearly half of all patients treated with LYRICA 600 mg/day had a 50% reduction in pain score. The response rates were comparable across the DPN and PHN programs. Similar proportions of LYRICA-treated patients had a 50% reduction in pain scores in the DPN (27-44%) and PHN studies (25-48%) across the mg/day dose range (see later slides). References Data on file, Pfizer Inc, New York, NY, USA Farrar et al. Pain 2001;94: Additional key words: diabetes, diabetic, postherpetic Dosis de pregabalina (mg/día) *50% de reducción en la puntuación del dolor desde el período inicial hasta el punto final en neuropatía diabética periférica y neuralgia postherpética Data on file, Pfizer Inc

Tasas altas de los que respondieron ( 30% reducción)* entre los 10 ensayos clínicos de dolor neuropático ***P0.001 vs. placebo *** *** 60% 51% *** % de pacientes 40% 30% This slide shows combined results from 10 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with neuropathic pain associated with DPN or PHN (studies 014, 029, 040, 131, 149, 030, 045, 127, 196, 155; 5-13 weeks duration). The results do not include LYRICA (pregabalin) 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which is included in the analysis, and one flexible-dose LYRICA mg/day arm). Patients were randomized to receive placebo or LYRICA 150, 300, or 600 mg/day. As LYRICA is renally excreted and dosage adjustment is required in renal impairment, in 3 studies, patients with low creatinine clearance (CLcr) (>30 and 60 mL/min) and randomized to the 600 mg/day group received a maximum dose of 300 mg/day, but were analyzed with the 600 mg/day group. In the remaining 7 studies, patients who had a creatinine clearance 60 mL/min were excluded. The primary efficacy variable was the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. A response was defined as having a 30% or 50% reduction in pain score from baseline to end point. The key talking points for this slide are as follows: The 30% responder rates are presented on this slide. A 30% reduction in the pain score has previously been shown to be clinically important (Farrar et al. 2001). The 30% responder rate was significantly higher with all three LYRICA doses than placebo. 40% of patients on pregabalin 150 mg/day had a ≥30% reduction in pain score, as did over 50% on pregabalin 300 mg/day. The 30% responder rate in the pregabalin 600 mg/day group (60%) was double that in the placebo group (30%). References Data on file, Pfizer Inc, New York, NY, USA Farrar et al. Pain 2001;94: Additional key words: diabetes, diabetic, postherpetic Dosis de pregabalina (mg/día) 30% de reducción en la puntuación del dolor desde el período inicial hasta el punto final en neuropatía diabética periférica y neuralgia postherpética Data on file, Pfizer Inc

Dolor neuropático periférico: Análisis continuo de los que respondieron*
% of patients 100 90 80 70 60 50 40 30 20 10 Pregabalina 600 mg/día Pregabalina 300 mg/día Pregabalina 150 mg/día Placebo % de pacientes This slide presents cumulative response data for each fixed LYRICA (pregabalin) dose and placebo, pooled, in 9 fixed-dose neuropathic pain trials (studies 014, 029, 040, 131, 149, 030, 045, 127, 196; 5-13 weeks duration). This analysis was conducted before the flexible/fixed dose study (study 155) was completed and therefore the fixed-dose 600 mg/day arm from this study is not included. The horizontal axis shows the % reduction in pain score from baseline to end point. The vertical axis shows the % of patients who had the % reduction in pain shown on the horizontal axis. The key talking points for this slide are as follows: The dose-response relationship for LYRICA and the superiority to placebo was consistent across all degrees of response to treatment. A ≥30% reduction in the pain score has previously been shown to be clinically important (Farrar et al. 2001). A ≥30% reduction in pain score was reported in over 40% of patients treated with LYRICA 150 mg/day, in over 50% on LYRICA 300 mg/day, and over 60% on LYRICA 600 mg/day, compared with only 30% on placebo. A ≥50% reduction is accepted to be clinically significant and is often used to compare treatment responses for different agents across clinical trials. A ≥50% reduction in pain score was reported in over 25% on LYRICA on 150 mg/day, over 30% on LYRICA 300 mg/day, and over 40% on LYRICA 600 mg/day, compared with only 20% on placebo. A ≥70% reduction in pain score, which represents a highly significant improvement in pain, was reported in approximately 25% on LYRICA 600 mg/day, compared with approximately 10% on placebo. These data further demonstrate that LYRICA mg day is effective in relieving pain and that some patients experience a highly significant improvement on LYRICA treatment. References Data on file, Pfizer Inc, New York, NY, USA Farrar et al. Pain 2001;94: Additional key words: diabetes, diabetic, postherpetic, responder 10 20 40 50 60 70 80 90 100 30 % de reducción en el dolor desde el período inicial * % de reducción en la puntuación del dolor desde el período inicial hasta el punto final Data on file, Pfizer Inc (9 estudios de dosis fija combinados)

Mejoría reportada por los pacientes entre los 10 ensayos clínicos de dolor neuropático periférico Impresión de cambio global del paciente (PGIC)* Peor Ningún cambio Mejorado *** *** P< vs. placebo *** *** % de pacientes This slide shows combined results from 10 double-blind, placebo-controlled, multicenter studies in patients 18 years of age with neuropathic pain associated with DPN or PHN (studies 014, 029, 040, 131, 149, 030, 045, 127, 196, 155; 5-13 weeks duration). Patients were randomized to receive placebo or LYRICA (pregabalin) 150, 300, or 600 mg/day. The results do not include LYRICA 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which is included in the analysis, and one flexible-dose LYRICA mg/day arm). As LYRICA is renally excreted and dosage adjustment is required in renal impairment, in 3 studies, patients with low creatinine clearance (CLcr) (>30 and 60 mL/min) and randomized to the 600 mg/day group received a maximum dose of 300 mg/day, but were analyzed with the 600 mg/day group. In the remaining 7 studies, patients who had a creatinine clearance 60 mL/min were excluded. Patients rated their global impression of change (PGIC) at end point (compared with baseline) on a 7-point categorical scale from 1=very much improved to 7=very much worse. Results were grouped according to if patients were worse, had no change or were improved at end point. Only those patients who had an end point assessment (upon discontinuation or completion) could be included in this analysis. As some patients did not complete their PGIC questionnaire, the patient numbers in this analysis are slightly lower than in the primary analysis, which was based on daily pain diaries (earlier slide). The key talking points for this slide are as follows: The patient global impression of change (PGIC) scale used in these studies is a global measure of effectiveness that indicates how patients might or might not be benefiting from treatment. The analysis tested the significance of the difference between each LYRICA group and the placebo group in the overall distribution of PGIC scores at end point. i.e. not any single PGIC category between LYRICA and placebo, but the relative distribution of categories in each treatment group. LYRICA 150, 300 and 600 mg/day were associated with significant improvements in overall status compared with placebo; the effect appeared to be dose related. Over 50% of patients on LYRICA 150 mg/day, 60% on 300 mg/day and 79% of patients who received LYRICA 600 mg/day reported significant improvements in their overall status. These data indicate that LYRICA mg/day is associated with significant global improvement in patients treated for peripheral neuropathic pain. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic Dosis de pregabalina (mg/día) *Medido en una escala de 7 puntos, condensado a 3 categorías Data on file, Pfizer Inc

Mejoría en la calidad de vida con pregabalina en dolor neuropático periférico: Puntuaciones medias de la SF-36 en el punto final a través de10 ensayos Pregabalina 150 mg/día (n=402) Pregabalina 300 mg/día (n=453) Pregabalina 600 mg/día (n=546) * P<0.05 vs. placebo * * * * * * * * * * * * * * * * * Puntuación media en el criterio de evaluación final de la SF-36 This slide presents pooled Short-Form 36 (SF-36) quality of life data from 10 double-blind, placebo-controlled, multicenter studies in patients 18 years of age with neuropathic pain associated with DPN or PHN (studies 014, 029, 040, 131, 149, 030, 045, 127, 196, 155). The results do not include LYRICA (pregabalin) 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which is included in the analysis, and one flexible-dose LYRICA mg/day arm). The SF-36 is a patient-completed questionnaire comprising 36 questions that evaluate 8 health concepts or domains of quality of life and functioning. Higher scores represent better quality of life and functioning. Mean end point scores in each LYRICA group were compared with placebo. The key talking points for this slide are as follows: LYRICA 300 and 600 mg/day were associated with significant improvements in 6 of the 8 domains of quality of life and functioning compared with placebo. The improvements observed with LYRICA encompassed a variety of domains including pain itself, as well as emotional and mental well-being, social functioning, vitality and overall perception of general health. These improvements indicate that the improvements in pain and pain-related sleep interference associated with LYRICA may result in improved quality of life across several domains. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic Limitación en la función física Función física Physical function Limitación en el rol físico Función social Dolor corporal Bodily pain Salud mental Mental health Emotional role Rol emocional Vitalidad Vitality General health perception Percepción generad de la salud Data on file, Pfizer Inc

Alivio efectivo del dolor en neuropatía diabética periférica y neuralgia postherpética
Neuralgia posthepérica Dosis de pregabalina (mg/día) Dosis de pregabalina (mg/día) *** Cambio medio desde el período inicial ** *** Cambio medio desde el período inicial *** *** This slide shows the pooled analysis of 10 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with neuropathic pain associated with DPN or PHN (studies 014, 029, 040, 131, 149, 030, 045, 127, 196, 155; 5-13 weeks duration). The results do not include LYRICA (pregabalin) 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which was included in the analysis, and one flexible-dose LYRICA mg/day arm). Patients were randomized to receive placebo or LYRICA 150, 300, or 600 mg/day. As LYRICA is renally excreted and dosage adjustment is required in renal impairment, in 3 studies, patients with low creatinine clearance (CLcr) (>30 and 60 mL/min) and randomized to the 600 mg/day group received a maximum dose of 300 mg/day, but were analyzed with the 600 mg/day group. In the remaining 7 studies, patients who had a creatinine clearance 60 mL/min were excluded. The primary efficacy variable was the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean change from baseline to end point was also compared. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean score across all groups approx. 6.5 in DPN and 6.6 in PHN) The improvement in pain from baseline to endpoint was significantly greater with LYRICA 150, 300 and 600 mg/day than placebo in both DPN and PHN patients. Efficacy was dose-related in both DPN and PHN patients Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic *** **P<0.01, ***P<0.001 vs. placebo ***P<0.001 vs. placebo Puntación media del dolor en el período inicial ~ 6.5 Puntación media del dolor en el período inicial ~ 6.6 Pacientes con neuropatía diabética periférica de 6 estudios, pacientes con neuralgia postherpética de 5 estudios combinados Data on file, Pfizer Inc

Pregabalina efectiva en neuropatía diabética periférica entre los estudios: diferencia en la puntuación media del dolor (intervalo de confianza de 95% ) de placebo en el criterio de evaluación Estudio 1 2 3 4 5 1 Diferencia media (IC 95%) -1 * * * * * -2 This slide shows results from 5 individual double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with DPN (studies 014, 029, 040, 131, 149; 5-12 weeks duration). Patients were randomized to receive placebo or LYRICA (pregabalin) 150, 300, or 600 mg/day. The primary efficacy variable was the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean pain score differences from placebo at end point, with 95% confidence intervals of the mean differences, are shown. The key talking points for this slide are as follows: LYRICA was effective in relieving neuropathic pain in 4 of 5 completed DPN studies. In one study (#3, 040), LYRICA 600 mg/day did not achieve statistical significance compared with placebo in the analysis of this end point. However, the planned analytic methods used for the primary end point in this study differed from all other registration studies. When analyzed, post-hoc, by the same method as the other studies, the study was positive (P=0.042). LYRICA 300 and 600 mg/day were both statistically and clinically significantly superior to placebo in relieving pain in most studies. Note: While this slide conveys a lot of important data, it is a complex slide, and is probably best presented as a back-up to address questions raised by pain specialists. It is probably not very meaningful to GPs. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic 150 600 300 600 600 300 150 300 600 -3 (n=79) (n=82) (n=81) (n=81) (n=86) (n=75) (n=96) (n=96) (n=98) Dosis de pregabalina (mg/día) *P<0.05 vs. placebo Data on file, Pfizer Inc

Alivio efectivo del dolor en neuropatía diabética periférica
Dosis de pregabalina (mg/día) ** Cambio medio desde el período inicial *** This slide shows the pooled analysis of data from 6 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with pain associated with DPN (studies 014, 029, 040, 131, 149 and 155; 5-12 weeks duration). The results do not include LYRICA (pregabalin) 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which is included in the analysis, and one flexible-dose LYRICA mg/day arm). Patients were randomized to receive placebo or LYRICA 150, 300, or 600 mg/day. As LYRICA is renally excreted and dosage adjustment is required in renal impairment, in one study, patients with low creatinine clearance (CLcr) (>30 and 60 mL/min) and randomized to the 600 mg/day group received a maximum dose of 300 mg/day, but were analyzed with the 600 mg/day group. In the remaining 5 studies, patients who had a creatinine clearance 60 mL/min were excluded. The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean change from baseline to end point was also compared. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean score across all groups approx. 6.5). The improvement in pain from baseline to end point was significantly greater with LYRICA 150, 300 and 600 mg/day than placebo. Efficacy was dose-related. References Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic *** **P<0.01, ***P<0.001 vs. placebo Puntuación media del dolor en el período inicial ~ 6.5 Pacientes con neuropatía diabética periférica de 6 estudios combinados Data on file, Pfizer Inc

Reducción efectiva en la interferencia del sueño relacionada con el dolor en neuropatía diabética periférica Dosis de pregabalina (mg/día) ** Cambio medio desde el período inicial *** This slide shows the pooled analysis of data from 6 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with pain associated with DPN (studies 014, 029, 040, 131, 149 and 155; 5-12 weeks duration). The results do not include LYRICA (pregabalin) 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which was included in the analysis, and one flexible-dose LYRICA mg/day arm). Patients were randomized to receive placebo or LYRICA 150, 300, or 600 mg/day. As LYRICA is renally excreted and dosage adjustment is required in renal impairment, in one study, patients with low creatinine clearance (CLcr) (>30 and 60 mL/min) and randomized to the 600 mg/day group received a maximum dose of 300 mg/day, but were analyzed with the 600 mg/day group. In the remaining 5 studies, patients who had a creatinine clearance 60 mL/min were excluded. The change from baseline to end point in the mean pain-related sleep interference score in each LYRICA group was compared with placebo. The key talking points for this slide are as follows: Patients had moderate pain-related sleep interference at baseline (mean score across all groups approx. 5.4) The improvement in pain-related sleep interference from baseline to endpoint was significantly greater with LYRICA 150, 300 and 600 mg/day than placebo. Efficacy was dose-related. References Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic *** **P<0.01, ***P<0.001 vs. placebo Puntuación media de interferencia en el sueño en el período inicial ~ 5.4 Pacientes con neuropatía diabética periférica de 6 estudios combinados Data on file, Pfizer Inc

Estudios de neuropatía diabética periférica : Mejoría reportada por los pacientes Impresión global de cambio del paciente (PGIC)* Peor Ningún cambio Mejorado *** *** P<0.001 vs. placebo *** % de pacientes This slide shows the pooled analysis of data from 6 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with pain associated with DPN (studies 014, 029, 040, 131, 149 and 155; 5-12 weeks duration). The results do not include LYRICA (pregabalin) 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which was included in the analysis, and one flexible-dose LYRICA mg/day arm). Patients were randomized to receive placebo or LYRICA 150, 300, or 600 mg/day. As LYRICA is renally excreted and dosage adjustment is required in renal impairment, in one study, patients with low creatinine clearance (CLcr) (>30 and 60 mL/min) and randomized to the 600 mg/day group received a maximum dose of 300 mg/day, but were analyzed with the 600 mg/day group. In the remaining 5 studies, patients who had a creatinine clearance 60 mL/min were excluded. Patients rated their global impression of change (PGIC) at end point (compared with baseline) on a 7-point categorical scale from 1=very much improved to 7=very much worse. Results were grouped according to if patients were worse, had no change or were improved at end point. Only those patients who had an end point assessment (upon discontinuation or completion) could be included in this analysis. As some patients did not complete their PGIC questionnaire, the patient numbers in this analysis are slightly lower than in the primary analysis, which was based on daily pain diaries (earlier slide). The key talking points for this slide are as follows: The patient global impression of change (PGIC) scale used in these studies is a global measure of effectiveness that indicates how patients might or might not be benefiting from treatment. The analysis tested the significance of the difference between each LYRICA group and the placebo group in the overall distribution of PGIC scores at end point. i.e. not any single PGIC category between LYRICA and placebo, but the relative distribution of categories in each treatment group. LYRICA 300 and 600 mg/day were associated with significant improvements in overall status compared with placebo; the effect appeared to be dose related. Over 70% of patients on LYRICA 300 mg/day and 80% of patients who received LYRICA 600 mg/day reported significant improvements in their overall status. These data indicate that a significant proportion of patients with DPN reported they improved on LYRICA treatment. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic Dosis de pregabalina (mg/día) *Medido en una escala de 7 puntos, condensada a 3 categorías Pacientes con neuropatía diabética periférica de 6 estudios combinados. Data on file, Pfizer Inc

Pregabalina efectiva en neuralgia postherpética entre los estudios: Diferencia en la puntuación media del dolor (95% IC) desde placebo hasta el criterio de evaluación Estudio 1 2 3 4 1 0.5 -0.5 * -1 * Diferencia media (95% IC) * -1.5 * * * -2 This slide shows results from 4 individual double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with PHN (studies 030, 045, 127, 196; 5-13 weeks duration). Patients were randomized to receive placebo or LYRICA (pregabalin) 150, 300, or 600 mg/day. The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean pain score differences from placebo at end point, with 95% confidence intervals of the mean differences, are shown. The key talking points for this slide are as follows: LYRICA was effective in relieving neuropathic pain in 3 of 4 completed PHN studies. The 150 mg/day dose of LYRICA did not reduce pain scores compared with placebo in study 1 (protocol 030), but it did in the other two studies in which it was evaluated (studies 2 and 4; protocols 045 and 196, respectively), suggesting that 150 mg/day is the minimally effective dose of LYRICA. LYRICA 150, 300 and 600 mg/day were statistically and clinically significantly superior to placebo in relieving pain. Note: While this slide conveys a lot of important data, it is a complex slide, and is probably best presented as a back-up to address questions raised by pain specialists. It is probably not very meaningful to GPs. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic -2.5 -3 150 150 300 600 150 300 600 (n=82) (n=81) (n=76) (n=88) (n=87) (n=98) (n=88) Dosis de pregabalina (mg/día) *P<0.05 vs. placebo Data on file, Pfizer Inc

Alivio efectivo del dolor en neuralgia postherpética
Dosis de pregabalina (mg/día) *** *** Cambio medio desde el período inicial *** This slide shows the pooled analysis of data from 5 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with PHN (studies 030, 045, 127, 196, 155 – 5-13 weeks duration). The results do not include LYRICA (pregabalin) 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which was included in the analysis, and one flexible-dose LYRICA mg/day arm). Patients were randomized to receive placebo or LYRICA 150, 300, or 600 mg/day. As LYRICA is renally excreted and dosage adjustment is required in renal impairment, in two studies, patients with low creatinine clearance (CLcr) (>30 and 60 mL/min) and randomized to the 600 mg/day group received a maximum dose of 300 mg/day, but were analyzed with the 600 mg/day group. In the remaining 3 studies, patients who had a creatinine clearance 60 mL/min were excluded. The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean change from baseline to end point was also compared. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean score across all groups approx. 6.6). The improvement in pain from baseline to end point was significantly greater with LYRICA 150, 300 and 600 mg/day than placebo. Efficacy was dose-related. References Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic ***P<0.001 vs. placebo Puntuación media del dolor desde el período inicial ~ 6.6 Pacientes con neuralgia postherpética de 5 estudios combinados Data on file, Pfizer Inc

Reducción efectiva en la interferencia del sueño relacionada con el dolor en neuralgia postherpética
Dosis de pregabalina (mg/día) *** *** Cambio medio desde el período inicial *** This slide shows the pooled analysis of data from 5 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with PHN (studies 030, 045, 127, 196, 155 – 5-13 weeks duration). The results do not include LYRICA (pregabalin) 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which was included in the analysis, and one flexible-dose LYRICA mg/day arm). Patients were randomized to receive placebo or LYRICA 150, 300, or 600 mg/day. As LYRICA is renally excreted and dosage adjustment is required in renal impairment, in two studies, patients with low creatinine clearance (CLcr) (>30 and 60 mL/min) and randomized to the 600 mg/day group received a maximum dose of 300 mg/day, but were analyzed with the 600 mg/day group. In the remaining 3 studies, patients who had a creatinine clearance 60 mL/min were excluded. The change from baseline to end point in the mean pain-related sleep interference score in each LYRICA group was compared with placebo. The key talking points for this slide are as follows: Patients had moderate pain-related sleep interference at baseline (mean score across all groups approx. 4.7). The improvement in pain-related sleep interference from baseline to endpoint was significantly greater with LYRICA 150, 300 and 600 mg/day than placebo. Efficacy was dose-related. References Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic ***P<0.001 vs. placebo Puntuación media de la interferencia del sueño en el período inicial ~ 4.7 Pacientes con neuralgia postherpética de 5 estudios combinados Data on file, Pfizer Inc

Estudios de neuralgia postherpética : Mejoría reportada por los pacientes Impresión global de cambio en el paciente (PGIC)* Peor Ningún cambio Mejorado *** P≤0.001 vs. placebo *** *** *** % de pacientes This slide shows the pooled analysis of data from 5 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with PHN (studies 030, 045, 127, 196, 155 – 5-13 weeks duration). The results do not include LYRICA (pregabalin) 75 mg/day (sub-therapeutic dose) or the flexible-dose arm of the PHN/DPN study (study 155 had one fixed-dose LYRICA 600 mg/day arm, which was included in the analysis, and one flexible-dose LYRICA mg/day arm). Patients were randomized to receive placebo or LYRICA 150, 300, or 600 mg/day. As LYRICA is renally excreted and dosage adjustment is required in renal impairment, in two studies, patients with low creatinine clearance (CLcr) (>30 and 60 mL/min) and randomized to the 600 mg/day group received a maximum dose of 300 mg/day, but were analyzed with the 600 mg/day group. In the remaining 3 studies, patients who had a creatinine clearance 60 mL/min were excluded. Patients rated their global impression of change (PGIC) at end point (compared with baseline) on a 7-point categorical scale from 1=very much improved to 7=very much worse. Results were grouped according to if patients were worse, had no change or were improved at end point. Only those patients who had an end point assessment (upon discontinuation or completion) could be included in this analysis. As some patients did not complete their PGIC questionnaire, the patient numbers in this analysis are slightly lower than in the primary analysis, which was based on daily pain diaries (earlier slide). The key talking points for this slide are as follows: The patient global impression of change (PGIC) scale used in these studies is a global measure of effectiveness that indicates how patients might or might not be benefiting from treatment. The analysis tested the significance of the difference between each LYRICA group and the placebo group in the overall distribution of PGIC scores at end point. i.e. not any single PGIC category between LYRICA and placebo, but the relative distribution of categories in each treatment group. LYRICA 150, 300 and 600 mg/day were all associated with significant improvements in overall status compared with placebo; the effect appeared to be dose related. Over 50% of patients on LYRICA 150 and 300 mg/day and 76% of patients who received LYRICA 600 mg/day reported significant improvements in their overall status. These data indicate that a significant proportion of patients with PHN reported they improved on LYRICA treatment. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic Dosis de pregabalina (mg/día) *Medido en una escala de 7 puntos; condensada a 3 categorías Pacientes con neuralgia postherpética de 5 estudios combinados. Data on file, Pfizer Inc

Uso de medicación concomitante a través de los estudios de neuralgia postherpética
Anticonvulsivante Opiáceos Antidepresivos Otros Cualquier medicación concomitante This slide shows combined results from 4 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with PHN (studies 030, 045, 127, 196). Patients were randomized to receive placebo or LYRICA (pregabalin) 150, 300, or 600 mg/day. In these studies, patients were allowed to remain on stable doses of analgesics and antidepressants. Patients who were taking anticonvulsants for pain were required to discontinue these agents before the study, However, if patients were taking anticonvulsants (AEDs) for indications other than pain, they were permitted to remain on treatment during the study. Thus, only a very small proportion of patients were taking these agents, and not as a prescribed treatment for their PHN-related pain. The key talking points for this slide are as follows: Over half the patients were receiving co-medications for their pain during these studies. Despite this, pain control was sub-optimal and patients had sufficiently high levels of pain to be enrolled in the studies. Approximately 20% of patients were taking antidepressants and/or opioids, yet their mean baseline pain scores were 6-7, indicating moderate to severe pain. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: concomitant, postherpetic % de pacientes A los pacientes con neuralgia posthepética se les permitió continuar con el medicamento concomitante estable durante los ensayos clínicos Data on file, Pfizer Inc

Cualquier medicamento
Efecto del tratamiento de pregabalina no impactado por la medicación concomitante en los estudios de neuralgia postherpética Diferencia media (95% IC) desde placebo This slide shows combined analyses from 4 double-blind, placebo-controlled, multicenter studies (both TID [three times daily] and BID [twice daily] dose regimens) in patients 18 years of age with PHN (studies 030, 045, 127, 196) Patients were randomized to receive placebo or LYRICA (pregabalin) 150, 300, or 600 mg/day. In these studies, patients were allowed to remain on stable doses of analgesics and antidepressants. The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean pain score differences from placebo at end point, with 95% confidence intervals of the mean differences, are shown. The key talking points for this slide are as follows: Over half of the patients were receiving co-medications for their pain during these studies. The treatment effect of LYRICA was similar among those who were taking concomitant medications and those who were not, in all three LYRICA dose groups. These data indicate that LYRICA is effective in relieving pain associated with PHN in patients who have significant pain whether or not they are taking other pain medications. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: concomitant, postherpetic Cualquier medicamento concomitante Ninguno Cualquier medicamento concomitante Ninguno Ninguno Cualquier medicamento concomitante Dosis diaria de pregabalina por uso de medicamento concomitante Data on file, Pfizer Inc

Efecto del tratamiento de pregabalina no impactado por la respuesta previa a gabapentina
Excluidos los que no respondieron a gabapentina Incluidos los que no respondieron a gabapentina Diferencia media (IC de 95%) de placebo This slide shows results from double-blind, placebo-controlled, multicenter studies of pregabalin in DPN (studies 014, 029, 040, 149), PHN studies (127, 196) and the DPN/PHN study (155). All of these studies included a pregabalin 600 mg/day arm. One of the DPN studies (149) and one of the PHN studies (196), and the DPN/PHN study (155) allowed patients who had previously failed to respond to gabapentin to enter. The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean pain score differences from placebo at end point, with 95% confidence intervals of the mean differences, are shown. The key talking points for this slide are as follows: The pregabalin 600 mg/day dose was selected to compare results between studies that excluded gabapentin non-responders and studies that permitted inclusion of non-responders as this was the most commonly studied dose across the trial program. Results were similar for the comparison of 150 and 300 mg/day according to the exclusion/inclusion of gabapentin non-responders. The flexible-dose mg/day dose arm for the DPN/PHN study is also shown on this slide. In both DPN and PHN, response to pregabalin treatment was similar in those studies that excluded and included previous gabapentin non-responders. The exclusion of gabapentin non-responders did not bias the validity of the pregabalin treatment effect. These data indicate that pregabalin is effective in patients who previously demonstrated non-response to gabapentin. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: gabapentin Estudios de neuropatía diabética periférica Estudios de neuralgia postherpética Estudios de neuropatía diabética periférica / neuralgia postherpética Dosis de 600 mg/día de pregabalina de los estudios individuales utilizada como ejemplo Data on file, Pfizer Inc

Dosis de pregabalina (fija)
Eficacia de pregabalina demostrada en 8 estudios de dolor neuropático periférico Dosis de pregabalina (fija) Estudio # 150 mg/día 300 mg/día 600 mg/día Neuropatía diabética periférica 014 (TID)   029 (TID) 131 (TID) 040 (TID) 149 (BID) Neuralgia postherpética 030 (TID) 127 (TID) 045 (TID ) 196 (BID) Neuropatía diabética periférica/ neuralgia postherpética 155 (BID)* This slides summarizes the significant and non-significant findings by dose studied in the analysis of the primary end point. Ticks represent those LYRICA (pregabalin) doses that were statistically significantly more effective than the placebo group in improving pain (P<0.05). The primary efficacy variable was, for all pain studies, the comparison of mean end point pain scores between each LYRICA group and the placebo group, based on pain scores from the last 7 days’ diary entries while patients were on treatment. Results from all 10 completed studies in neuropathic pain are summarized (only 600 mg/day fixed-dose arm of study 155; study 155 was a 12-week study in DPN/PHN and included one LYRICA 600 mg/day fixed-dose arm and one LYRICA mg/day flexible-dose arm). This slide includes only results for fixed-dose LYRICA. The key talking points for this slide are as follows: Only those doses studied are marked with a tick or cross (blanks indicates that the dose was not studied) LYRICA 150 mg/day was associated with a significant improvement in pain compared with placebo in 2 out of 3 PHN studies. LYRICA 300 mg/day was associated with a significant improvement in pain compared with placebo in 4 out of 5 studies LYRICA 600 mg/day was associated with a significant improvement in pain compared with placebo in 6 out of 7 studies. In study 040, the improvement seen with LYRICA 600 mg/day just failed to reach statistical significance in the primary analysis (P=0.082). Flexible-dose LYRICA mg/day (study 155) was also significantly more effective than placebo but is not shown on the slide, which shows only the fixed-dose arms. Based on the results of these studies, the recommended dose range for LYRICA in peripheral neuropathic pain is mg/day taken in a BID (twice daily) or a TID (three times daily) dosing schedule. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetic, diabetes, postherpetic  = no significativo  = P<0.05 en el criterio de evaluación primario del dolor Data on file, Pfizer Inc *Dosis flexible de pregabalina de mg/día también significativamente superior a placebo

 = No significativo  = P<0.05
Criterios de evaluación secundarios positivos frente a Placebo en estudios de dolor neuropático periférico con dosis fija Estudio # 150 mg/día 300 mg/día 600 mg/día Neuropatía diabética periférica PGIC CGIC Sueño SF-MPQ 014 (TID)   029 (TID) 131 (TID) 040 (TID) 149 (BID) Neuralgia postherpética 030 (TID) 127 (TID) 045 (TID) 196 (BID) /Neuralgia postherpética 155 (BID) This slides summarizes the significant and non-significant findings by dose studied in the analysis of secondary end points. Ticks represent those LYRICA (pregabalin) doses that were statistically significantly more effective than the placebo group in improving the variable shown (P<0.05). Results from all 10 completed studies in neuropathic pain are summarized (only 600 mg/day fixed-dose arm of study 155; study 155 was a 12-week study in DPN/PHN and included one LYRICA 600 mg/day fixed-dose arm and one LYRICA mg/day flexible-dose arm). This slide includes only results for fixed-dose LYRICA. The key talking points for this slide are as follows: Only those doses and assessments studied are marked with a tick or cross (blanks indicates dose was not studied or assessment not conducted). The patient and clinical global impressions of change from baseline at end point (PGIC and CGIC) indicate that patients rated themselves, and clinicians rated patients, as improved, in most studies of LYRICA 300 and 600 mg/day. Overall these results indicate that LYRICA is consistently associated with global improvement as rated by both patients and clinicians. Sleep interference improved significantly in all studies of LYRICA 600 and 300 mg/day and in 3 out of 5 studies of LYRICA 150 mg/day, indicating that LYRICA is consistently associated with a significant improvement in sleep across the dose range. The SF-McGill Pain Questionnaire (SF-MPQ) pain visual analogue scale (VAS) results also demonstrated that LYRICA was consistently effective in improving pain, corroborating the findings of the primary end point analysis of mean pain diary scores. Flexible-dose LYRICA mg/day (study 155) was also significantly more effective than placebo on all assessments shown on this table for that study, but is not shown on the slide which includes only fixed-dose arms. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetic, diabetes, postherpetic  = No significativo  = P<0.05 Sueño= Interferencia de sueño. SF-MPQ = VAS del dolor Data on file, Pfizer Inc

Eficacia de pregabalina en el dolor neuropático periférico
Resultados de los estudios claves en neuralgia postherpética

Pregabalina efectiva en neuralgia postherpética: Alivio rápido y sostenido del dolor
Placebo (n = 81) Pregabalina 150 mg/día (n = 81) Pregabalina 300 mg/día (n = 76) * * * * * * * * * Puntuación media del dolor * * * * * * * * * This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of postherpetic neuralgia (PHN) (study 045). Patients were randomized to, and treated with, LYRICA 150 mg/day (n=81) and 300 mg/day (n=76) or placebo (n=81), taken in a TID (three times daily) dosing schedule. Patients in the LYRICA 150 mg/day and 300 mg/day groups were escalated to these doses over the first week. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score for all groups ranged from ). LYRICA 150 and 300 mg/day were significantly effective in improving pain as early as 1 week, and for the duration of the 8-week study. LYRICA 150 and 300 mg/day were significantly more effective in improving pain than placebo at end point. Efficacy was dose-related, and clinically significant. Reference Sabatowski et al. Pain. 2004;109(1-2):26-35 Additional key words: postherpetic, rapid, sustained *P<0.01 cada dosis de pregabalina vs. placebo semanas 1 – 8 y punto final *P<0.01 each pregabalin dose vs. placebo weeks 1-8 and end point Final Semana Sabatowski et al. Pain. 2004;109(1-2):26-35

*P<0.05 each pregabalin dose vs. placebo weeks 1-8
Pregabalina efectiva en neuralgia postherpética : Alivio rápido y sostenido del dolor *P<0.05 each pregabalin dose vs. placebo weeks 1-8 *P<0.05 cada dosis de pregabalina vs. placebo semanas 1 - 8 * * * * * * * * * * Cambio medio en la puntuación del dolor * * * * * * Placebo (n = 81) This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of postherpetic neuralgia (PHN) (study 045). Patients were randomized to, and treated with, LYRICA 150 mg/day (n=81) and 300 mg/day (n=76) or placebo (n=81), taken in a TID (three times daily) dosing schedule. Patients in the LYRICA 150 mg/day and 300 mg/day groups were escalated to these doses over the first week. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly scores were also compared. This slide shows the mean change from baseline throughout the study. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score for all groups ranged from ). LYRICA 150 and 300 mg/day were significantly effective in improving pain as early as 1 week, and for the duration of the 8-week study. LYRICA 150 and 300 mg/day were also significantly more effective in improving pain than placebo at end point. Efficacy was dose-related, and clinically significant. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic, rapid, sustained Pregabalina 150 mg/día (n = 81) Pregabalina 300 mg/día (n = 76) Semana La puntuación media en el período inicial fue de 6.6 – 7.0 Data on file, Pfizer Inc

Pregabalina en neuralgia postherpética: Mejoría rápida en la interferencia del sueño relacionada con el dolor *P<0.01 pregabalina vs. placebo Placebo (n = 81) Pregabalina 150 mg/día (n = 81) Pregabalina 300 mg/día (n = 76) Puntuación media de interferencia del sueño * * * * * * * * * * * * * This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of postherpetic neuralgia (PHN) (study 045). Patients were randomized to, and treated with, LYRICA 150 mg/day (n=81) and 300 mg/day (n=76) or placebo (n=81), taken in a TID (three times daily) dosing schedule. Patients in the LYRICA 150 mg/day and 300 mg/day groups were escalated to these doses over the first week. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The mean end point pain-related sleep interference score in each LYRICA group was compared with placebo. Mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate sleep interference at baseline (mean sleep interference score for all groups ranged from ). LYRICA 150 and 300 mg/day were significantly more effective than placebo in improving pain-related sleep interference as early as 1 week and for the duration of the 8-week study. Reference Sabatowski et al. Pain. 2004;109(1-2):26-35 Additional key words: postherpetic, rapid, sustained * * * * * Final Semana Sabatowski et al. Pain. 2004;109(1-2):26-35

*P<0.01 cada dosis de pregabalina vs. placebo
Pregabalina en neuralgia postherpética: Alivio rápido y sostenido del dolor y reducción en la interferencia del sueño relacionado con el dolor Dolor Interferencia del sueño Puntuación media Puntuación media * * * * * * * * * * * * * * * * * * Final Final This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of postherpetic neuralgia (PHN) (study 045). Patients were randomized to, and treated with, LYRICA 150 mg/day (n=81) and 300 mg/day (n=76) or placebo (n=81), taken in a TID (three times daily) dosing schedule. Patients in the LYRICA 150 mg/day and 300 mg/day groups were escalated to these doses over the first week. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly and end point pain and sleep interference scores (a measure of the extent to which pain disturbed sleep) in each LYRICA group were compared with placebo. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score for all groups ranged from ). Patients had moderate sleep interference at baseline (mean sleep interference score for all groups ranged from ) . LYRICA 150 and 300 mg/day were significantly more effective in improving pain than placebo at end point. Efficacy was dose-related, and clinically significant. LYRICA 150 and 300 mg/day were significantly effective in improving pain as early as 1 week, and for the duration of the 8-week study. LYRICA 150 and 300 mg/day were also significantly more effective than placebo in improving pain-related sleep interference as early as 1 week, and for the duration of the 8-week study. These data indicate that LYRICA 150 and 300 mg/day were significantly effective in relieving pain and reducing pain-related sleep interference in patients with PHN. Reference Sabatowski et al. Pain. 2004;109(1-2):26-35 Additional key words: postherpetic, rapid, sustained Semana Semana Placebo (n = 81) *P<0.01 cada dosis de pregabalina vs. placebo semanas 1 – 8 y final Pregabalina 150 mg/día (n = 81) Pregabalina 300 mg/día (n = 76) Sabatowski et al. Pain. 2004;109(1-2):26-35

Pregabalina efectiva en neuralgia postherpética : Alivio rápido y sostenido del dolor
Placebo (n = 84) *P0.01 vs. placebo Pregabalina 600 mg/día (n = 89) Puntuación media del dolor * * * * * * * * * This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of postherpetic neuralgia (PHN) (study 127). Patients were randomized to, and treated with, LYRICA 300/600 mg/day (n=89) or placebo (n=84), taken in a TID (three times daily) dosing schedule. Patients with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). Patients randomized to LYRICA received 150 mg/day for days 1-3 then 300 mg/day on day 4. At the end of the first week, patients with a CLcr >60 mL/min received 600 mg/day. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score for both groups ranged from ). LYRICA was significantly more effective in improving pain than placebo as early as 1 week, and for the duration of the 8-week study. Significantly greater pain relief was achieved with LYRICA compared with placebo from the second day of the study (see next slide and Dworkin paper page 1279). Note: This slide is hyperlinked to the next slide. In full screen view, if you pass the mouse cursor over the figure the “hand” will appear and when right-clicked once this will take you automatically to the next slide, which provides further data on the rapidity of onset of efficacy. Reference Dworkin et al. LYRICA for the treatment of postherpetic neuralgia. Neurology 2003;60: Additional key words: rapid, sustained Final Semanas Dworkin et al. Neurology, 2003;60:

Pregabalina efectiva en neuralgia postherpética: Alivio rápido del dolor
Días Semanas Placebo Pregabalina Placebo Pregabalina Puntuación media del dolor Puntuación media del dolor * * * * * * * * * * * * * * *P<0.01 vs. placebo *P<0.01 vs. placebo This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (PHN) (study 127). Patients were randomized to, and treated with, LYRICA 300/600 mg/day (n=89) or placebo (n=84), taken in a TID (three times daily) dosing schedule. Patients with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). Patients randomized to LYRICA received 150 mg/day for days 1-3 then 300 mg/day on day 4. At the end of the first week, patients with a CLcr >60 mL/min received 600 mg/day. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time in the analysis of weekly mean pain scores are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. To establish the rapidity of onset of efficacy, mean pain daily diary scores were analyzed by day during the first week of treatment. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score for both groups ranged from ). LYRICA was significantly more effective in improving pain than placebo as early as 1 week, and for the duration of the 8-week study. Significantly greater pain relief was achieved with LYRICA compared with placebo from the second day of the study (see Dworkin paper page 1279). These data indicate that even with escalation from the minimally effective dose (150 mg/day), the onset of pain relief is rapid with LYRICA treatment. Reference Dworkin et al. LYRICA for the treatment of postherpetic neuralgia. Neurology 2003;60: Additional key words: rapid, sustained Día Semana Dosis de pregabalina 150 mg/día 300 mg/día 600 mg/día Dworkin et al. Neurology, 2003;60:

Dworkin et al. Neurology, 2003;60:1274-1283
Pregabalina en neuralgia postherpética : Reducción rápida y sostenida en la interferencia del sueño relacionada con el dolor Placebo (n = 84) *P0.01 vs. placebo Pregabalina 600 mg/día (n = 89) Puntuación media en la interferencia del sueño This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (PHN) (study 127). Patients were randomized to, and treated with, LYRICA 300/600 mg/day (n=89) or placebo (n=84), taken in a TID (three times daily) dosing schedule. Patients with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). Patients randomized to LYRICA received 150 mg/day for days 1-3 then 300 mg/day on day 4. At the end of the first week, patients with a CLcr >60 mL/min received 600 mg/day. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The mean end point pain-related sleep interference score (a measure of the extent to which pain disturbed sleep) in each LYRICA group was compared with placebo. Mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate sleep interference at baseline (mean sleep interference score for both groups was 4.4). LYRICA was significantly more effective in improving pain-related sleep interference than placebo as early as week 1 and for the duration of the 8-week study. Reference Dworkin et al. Pregabalin for the treatment of postherpetic neuralgia. Neurology. 2003;60: Additional key words: rapid, sustained * * * * * * * * * Final Semana Dworkin et al. Neurology, 2003;60:

Pregabalina en neuralgia postherpética :
Dolor Interferencia del sueño Puntuación media Puntuación media * * * * * * * * * * * * * * * * * * This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (PHN) (study 127). Patients were randomized to, and treated with, LYRICA 300/600 mg/day (n=89) or placebo (n=84), taken in a TID (three times daily) dosing schedule. Patients with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). Patients randomized to LYRICA received 150 mg/day for days 1-3 then 300 mg/day on day 4. At the end of the first week, patients with a CLcr >60 mL/min received 600 mg/day. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly and end point pain and sleep interference scores (a measure of the extent to which pain disturbed sleep) in the LYRICA group were compared with placebo The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score for both groups ranged from ). Patients had moderate sleep interference at baseline (mean sleep interference score for both groups was 4.4). LYRICA was significantly more effective in improving pain than placebo as early as 1 week, and for the duration of the 8-week study. LYRICA was significantly more effective than placebo in improving pain-related sleep interference as early as 1 week, and for the duration of the 8-week study. These data indicate that LYRICA 600 mg/day was significantly effective in relieving pain and reducing pain-related sleep interference in patients with PHN. Reference Dworkin et al. Pregabalin for the treatment of postherpetic neuralgia. Neurology. 2003;60: Additional key words: postherpetic, rapid, sustained Final Final Semana Semana Placebo (n = 84) *P≤0.01 vs. placebo Pregabalina 600 mg/día (n = 89) Dworkin et al. Neurology, 2003;60:

en puntuación media del dolor en puntuación media del dolor
Pregabalina efectiva en neuralgia postherpética1: Reducción del dolor ‘clínicamente importante’2 Pregabalina 600 mg/día (n = 89) * P= vs. placebo * 63% * 50% % de pacientes 25% 20% This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (PHN) (study 127). Patients were randomized to, and treated with, LYRICA 300/600 mg/day (n=89) or placebo (n=84), taken in a TID (three times daily) dosing schedule. Patients with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). Patients randomized to LYRICA received 150 mg/day for days 1-3 then 300 mg/day on day 4. At the end of the first week, patients with a CLcr >60 mL/min received 600 mg/day. Response rates were defined as the proportion of patients with a 30% and a 50% reduction in their pain score from baseline at end point. The response rates in the LYRICA group were compared with the placebo group. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score for both groups ranged from ). A 30% reduction in the pain score has previously been shown to be clinically important (Farrar et al. 2001); a 50% reduction is accepted to be clinically significant and is often used to compare treatment responses for different agents across clinical trials. Significant and substantial proportions of patients had 30% and 50% reductions in pain. These data indicate that LYRICA 600 mg/day was effective in providing meaningful pain relief in patients with PHN. References Dworkin et al. Pregabalin for the treatment of postherpetic neuralgia. Neurology. 2003;60: Farrar et al. Pain 2001;94:  30% disminución en puntuación media del dolor  50% disminución en puntuación media del dolor 1. Dworkin et al. Neurology 2003;60: Farrar et al. Pain 2001;94:

Estudio de 13 semanas en neuralgia postherpética: Antecedentes
Tratamiento del estudio Pregabalina 150, 300 y 600 mg/día frente a placebo Dosis de 600 mg estratificada de acuerdo con CLcr (300 mg/día con CLcr 30–60 mL/min; 600 mg/día con CLcr 60 mL/min) Dosificación BID Tratamiento de 13 semanas, 1 semana con escala de dosis, dosis aleatorizada durante 12 semanas Analgésicos concomitantes permitidos (estables previos al estudio y durante el estudio, excluyendo anticonvulsivantes) Características del período inicial 366 pacientes tratados Edad media = 71 años (18-92) Duración media de PHN = 3.5 años Puntuación media del dolor en el período inicial (SD) = 6.7 (1.5) 53% con analgésicos concomitantes 23% paracetamol, 12% amitriptilina, 6% tramadol This slide describes the background and baseline characteristics in a 13-week, multicenter, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (study 196). Patients were randomized to, and treated with, LYRICA 150 mg (n=87), 300 mg (n=98), 600 mg (n=88) or placebo (n=93) taken in a BID (twice daily) dosing schedule. Patients randomized to LYRICA 600 mg were stratified according to baseline creatinine clearance; those with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). The study design and patient selection criteria were similar to the earlier PHN TID (three times daily) dosing studies. e.g. pain for 3 months after healing of herpes zoster rash, clinically relevant baseline pain, allowed to continue stable analgesics. The key talking points for this slide are as follows: The baseline characteristics in this study were similar to earlier studies and representative of the broader population with PHN. The mean baseline score indicated moderate to severe pain (mean baseline score 6.7). Half the patients were taking concomitant medications for pain. The three most common were paracetamol, amitriptyline and tramadol. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic Data on file, Pfizer Inc

**P<0.01 cada dosis de pregabalina vs. placebo
Estudio en neuralgia postherpética : Mejoría temprana y sostenida en el dolor Pregabalina 150 mg/día (n = 87) Pregabalina 300 mg/día (n = 98) Pregabalina 600 mg/día (n = 88) ** ** Puntuación media del dolor ** ** ** ** ** ** ** ** ** ** ** ** ** ** This slide presents data from a 13-week, multicenter, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (study 196). Patients were randomized to, and treated with, LYRICA 150 mg (n=87), 300 mg (n=98), 600 mg (n=88) or placebo (n=93) taken in a BID (twice daily) dosing schedule. Patients randomized to LYRICA 600 mg were stratified according to baseline creatinine clearance; those with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score was 6.7). Significant improvements in pain scores were observed for all LYRICA doses compared with placebo. LYRICA 150, 300 and 600 mg/day, dosed BID, were all significantly more effective than placebo in improving pain as early as week 1, and for the duration of the 13-week study. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic, rapid, sustained **P<0.01 cada dosis de pregabalina vs. placebo Semanas 1-13 y punto final Final Semana Data on file, Pfizer Inc

**P<0.01 cada dosis de pregabalina frente a placebo semanas 1-13
Estudio en neuralgia postherpética : Mejoría temprana y sostenida en el dolor **P<0.01 cada dosis de pregabalina frente a placebo semanas 1-13 ** Cambio medio en la puntuación del dolor ** ** ** ** ** ** ** ** This slide presents data from a 13-week, multicenter, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (study 196). Patients were randomized to, and treated with, LYRICA 150 mg (n=87), 300 mg (n=98), 600 mg (n=88) or placebo (n=93) taken in a BID (twice daily) dosing schedule. Patients randomized to LYRICA 600 mg were stratified according to baseline creatinine clearance; those with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly scores were also compared. This slide shows the mean change from baseline throughout the study. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score was 6.7). Significant improvements in pain scores were observed for all LYRICA doses compared with placebo. LYRICA 150, 300 and 600 mg/day, dosed BID, were all significantly more effective than placebo in improving pain as early as week 1 and for the duration of the 13-week study. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic, rapid, sustained Placebo (n = 93) ** ** ** Pregabalina 150 mg/día (n = 87) Pregabalina 300 mg/día (n = 98) Pregabalina 600 mg/día (n = 88) Semana La puntuación media del dolor en el período inicial fue 6.7 Data on file, Pfizer Inc

**P<0.01 cada dosis de pregabalina frente a placebo
Estudio en neuralgia postherpética : Mejoría temprana y sostenida en la interferencia del sueño relacionada con el dolor Placebo (n = 93) Pregabalina 150 mg/día (n = 87) Pregabalina 300 mg/día (n = 98) Pregabalina 600 mg/día (n = 88) **P<0.01 cada dosis de pregabalina frente a placebo semanas 1-13 y punto final Puntuación media en la interferencia del sueño ** ** This slide presents data from a 13-week, multicenter, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (study 196). Patients were randomized to, and treated with, LYRICA 150 mg (n=87), 300 mg (n=98), 600 mg (n=88) or placebo (n=93) taken in a BID (twice daily) dosing schedule. Patients randomized to LYRICA 600 mg were stratified according to baseline creatinine clearance; those with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The mean end point pain-related sleep interference score (a measure of the extent to which pain disturbed sleep) in each LYRICA group was compared with placebo. Mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate sleep interference at baseline (mean sleep interference score across groups range from ). Significant improvements in pain-related sleep interference scores were observed for all LYRICA doses compared with placebo. LYRICA 150, 300 and 600 mg/day, dosed BID, were all significantly more effective than placebo in reducing pain-related sleep interference as early as week 1 and for the duration of the 13-week study. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic, rapid, sustained ** ** ** ** ** ** ** ** ** ** ** ** ** ** Final Semana Data on file, Pfizer Inc

Estudio en neuralgia postherpética : Reducción rápida y sostenida del dolor e interferencia en el sueño relacionada con el dolor Dolor Interferencia del sueño *P<0.01 cada dosis de pregabalina frente a placebo semanas 1-13 y punto final *P<0.01 cada dosis de pregabalina frente a placebo semanas 1-13 y punto final Puntuación media Puntuación media * * * * * * * * * * * * * * * * * * * * * * * * * * * * Final Final This slide presents data from a 13-week, multicenter, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (study 196). Patients were randomized to, and treated with, LYRICA 150 mg (n=87), 300 mg (n=98), 600 mg (n=88) or placebo (n=93) taken in a BID (twice daily) dosing schedule. Patients randomized to LYRICA 600 mg were stratified according to baseline creatinine clearance; those with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). Patients in the 300 and 600 mg/day groups were escalated to these doses over the first week. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly and end point pain and sleep interference scores (a measure of the extent to which pain disturbed sleep) in each LYRICA group were compared with placebo. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score was 6.7). Patients had moderate sleep interference at baseline (mean sleep interference score across groups range from ). LYRICA 150, 300 and 600 mg/day were all significantly more effective than placebo in improving pain and pain-related sleep interference as early as week 1, and for the duration of the 13-week study. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic, rapid, sustained Semana Semana Placebo (n=93) Pregabalina 150 mg/día (n=87) Pregabalina 300 mg/día (n=97) Pregabalina 600 mg/día (n=88) Data on file, Pfizer Inc

Estudio en neuralgia postherpética: Tasas de los que respondieron ( 50% de reducción del dolor)* *** P=0.001 vs. placebo *** 38% *** *** % de pacientes 27% 26% This slide presents data from a 13-week, multicenter, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (study 196). Patients were randomized to, and treated with, LYRICA 150 mg (n=87), 300 mg (n=98), 600 mg (n=88) or placebo (n=93) taken in a BID (twice daily) dosing schedule. Patients randomized to LYRICA 600 mg were stratified according to baseline creatinine clearance; those with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). Response rates were defined as the proportion of patients with a 30% and a 50% reduction in their pain score from baseline at end point. The response rates in the LYRICA group were compared with the placebo group. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score 6.7). The 50% responder rates are presented on this slide. A 30% reduction in the pain score has previously been shown to be clinically important (Farrar et al. 2001); a 50% reduction is accepted to be clinically significant and is often used to compare treatment responses for different agents across clinical trials. Significantly more LYRICA-treated patients had a 50% reduction in pain at end point compared with placebo. These data indicate that LYRICA mg/day, dosed BID, is highly effective in relieving pain associated with PHN. References Data on file, Pfizer Inc, New York, NY, USA Farrar et al. Pain 2001;94: Additional key words: postherpetic 8% Dosis de pregabalina (mg/día) *50% de reducción en la puntuación del dolor desde el período inicial hasta el punto final Data on file, Pfizer Inc

Estudio en neuralgia postherpética : Tasas de los que respondieron ( 30% de reducción en el dolor)* *** P<0.001 vs. placebo *** 52% *** *** 41% 39% % de pacientes 17% This slide presents data from a 13-week, multicenter, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (study 196). Patients were randomized to, and treated with, LYRICA 150 mg (n=87), 300 mg (n=98), 600 mg (n=88) or placebo (n=93) taken in a BID (twice daily) dosing schedule. Patients randomized to LYRICA 600 mg were stratified according to baseline creatinine clearance; those with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). Response rates were defined as the proportion of patients with a 30% and a 50% reduction in their pain score from baseline at end point. The response rates in the LYRICA group were compared with the placebo group. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score 6.7). The 30% responder rates are presented on this slide. A ≥30% reduction in the pain score has previously been shown to be clinically important (Farrar et al. 2001). Significantly more LYRICA-treated patients had a clinically important (30%) reduction in pain compared with placebo. These data indicate that LYRICA mg/day, dosed BID, is highly effective in relieving pain associated with PHN. References Data on file, Pfizer Inc, New York, NY, USA Farrar et al. Pain 2001;94: Additional key words: postherpetic Dosis de pregabalina (mg/día) *30% de reducción en la puntuación del dolor desde el período inicial hasta el punto final Data on file, Pfizer Inc

Pregabalina: Alivio efectivo del dolor en neuralgia postherpética
Puntuación media del dolor Respondieron (50%)* *** P<0.001 vs. placebo Pregabalina 150 mg/día (n = 87) *** Pregabalina 300 mg/día (n = 98) Pregabalina 600 mg/día (n = 88) 38% *** *** Puntuación media % de pacientes 26% 27% * * * * * * * * * * * * * * This slide presents data from a 13-week, multicenter, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of post-herpetic neuralgia (study 196). Patients were randomized to, and treated with, LYRICA 150 mg (n=87), 300 mg (n=98), 600 mg (n=88) or placebo (n=93) taken in a BID (twice daily) dosing schedule. Patients randomized to LYRICA 600 mg were stratified according to baseline creatinine clearance; those with CLcr >60 mL/min received LYRICA 600 mg/day and those with CLcr >30 and ≤60 mL/min received LYRICA 300 mg/day because plasma levels would have been higher as a result of renal impairment (equivalent to 600 mg/day in patients with normal renal function). Patients in the 150 mg/day group received this dose from the start of the study. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly scores and ≥50% responder rates were also compared. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean score 6.7). LYRICA 150, 300 and 600 mg/day, dosed BID, were all significantly more effective than placebo in improving pain as early as week 1 and for the duration of 13-week study. Significantly more LYRICA-treated patients had a 50% reduction in pain at endpoint compared with placebo. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: postherpetic, rapid, sustained 8% Final Semana Dosis de pregabalina (mg/día) *P<0.01 cada dosis de pregabalina vs. placebo Semanas y punto final *50% de reducción en la puntuación del dolor desde el período inicial hasta el punto final Data on file, Pfizer Inc

Resultados de estudios clave de neuropatía diabética periférica

Pregabalina efectiva en neuropatía diabética periférica: Reducción rápida del dolor
*P<0.001 vs. placebo Pregabalina 75 mg/día (n = 77) Pregabalina 300 mg/día (n = 81) Pregabalina 600 mg/día (n = 82) * Punturación media del dolor * * * * * * * * * * * This slide presents data from a 5-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of painful diabetic peripheral neuropathy (DPN) (study 029). Patients were randomized to, and treated with, LYRICA 75 mg/day (n=77), 300 mg/day (n=81) and 600 mg/day (n=82) or placebo (n=97), taken in a TID (three times daily) dosing schedule. Patients in the 75 and 300 mg/day groups received their full randomized dose from the start of the study. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score for all groups ranged from ). LYRICA 300 and 600 mg/day were significantly more effective in improving pain than placebo as early as week 1, and for the duration of the 5-week study. LYRICA 75 mg/day was no more effective than placebo and is not within the therapeutic dose range. The therapeutic dose range is mg/day. Reference Lesser et al. Neurology. 2004: In Press Additional key words: diabetes, diabetic, rapid Final Semanas Lesser et al. Neurology. 2004: In Press

Pregabalina en neuropatía diabética periférica : Mejoría rápida en la interferencia del sueño relacionada con el dolor *P<0.001 vs. placebo Pregabalina 75 mg/día (n = 77) Pregabalina 300 mg/día (n = 81) Pregabalina 600 mg/día (n = 82) Puntuación media en la interferencia del sueño * * * * * * * This slide presents data from a 5-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of painful diabetic peripheral neuropathy (DPN) (study 029). Patients were randomized to, and treated with, LYRICA 75 mg/day (n=77), 300 mg/day (n=81) and 600 mg/day (n=82) or placebo (n=97), taken in a TID (three times daily) dosing schedule. Patients in the 75 and 300 mg/day groups received their full randomized dose from the start of the study. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The mean end point pain-related sleep interference score (a measure of the extent to which pain disturbed sleep) in each LYRICA group was compared with placebo. Mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate sleep interference at baseline (mean sleep interference score for all groups ranged from ). LYRICA 300 and 600 mg/day were significantly more effective in reducing pain-related sleep interference than placebo as early as week 1, and for the duration of the 5-week study. LYRICA 75 mg/day was no more effective than placebo and is not within the therapeutic dose range. The therapeutic dose range is mg/day. Reference Lesser et al. Neurology. 2004: In Press Additional key words: diabetes, diabetic, rapid * * * * * Final Semana Lesser et al. Neurology. 2004: In Press

Estudio en neuropatía diabética periférica: Mejoría en el dolor y reducción en la interferencia del sueño relacionado con el dolor Dolor Interferencia del sueño *P 0.001 vs. placebo *P 0.001 vs. placebo * Puntuación media Puntuación media * * * * * * * * * * * * * * * * * * * * * * * This slide presents data from a 5-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of painful diabetic peripheral neuropathy (DPN) (study 029). Patients were randomized to, and treated with, LYRICA 75 mg/day (n=77), 300 mg/day (n=81) and 600 mg/day (n=82) or placebo (n=97), taken in a TID (three times daily) dosing schedule. Patients in the 75 and 300 mg/day groups received their full randomized dose from the start of the study. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly and end point pain and sleep interference scores (a measure of the extent to which pain disturbed sleep) in each LYRICA group were compared with placebo The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score for all groups ranged from ). Patients had moderate sleep interference at baseline (mean sleep interference score for all groups ranged from ). LYRICA 300 and 600 mg/day were significantly more effective in improving pain than placebo as early as week 1, and for the duration of the 5-week study. LYRICA 300 and 600 mg/day were also significantly more effective than placebo in improving pain-related sleep interference as early as week 1, and for the duration of the 5-week study. LYRICA 75 mg/day was no more effective than placebo and is not within the therapeutic dose range. The therapeutic dose range is mg/day. Reference Lesser et al. Neurology. 2004: In Press Additional key words: diabetes, diabetic, rapid Final Final Semana Semana Pregabalina 75 mg/día (n = 77) Pregabalina 300 mg/día (n = 81) Pregabalina 600 mg/día (n = 82) Lesser et al. Neurology. 2004: In Press

Pregabalina efectiva en neuropatía diabética periférica: Reducción rápida del dolor
Placebo (n = 70) Pregabalina 300 mg/día (n = 76) Puntuación media del dolor *** *** *** *** *** *** ** ** *** This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of painful diabetic peripheral neuropathy (DPN) (study 131). Patients were randomized to, and treated with, LYRICA 300 mg/day (n=76) or placebo (n=70), taken in a TID (three times daily) dosing schedule. Patients in the LYRICA group received 300 mg/day from the start of the study. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score was across both groups). LYRICA 300 mg/day was significantly more effective in improving pain than placebo as early as week 1, and for the duration of the 8-week study. Reference Rosenstock et al. Pain.2004;110:628-38 Additional key words: diabetes, diabetic, rapid, sustained **P<0.01; ***P<0.001 vs. placebo Final Semana Rosenstock et al. Pain.2004;110:628-38

Pregabalina en neuropatía diabética periférica: Mejoría rápida en la interferencia del sueño relacionada con el dolor Placebo (n = 70) Pregabalina 300 mg/día (n = 76) **P<0.01; ***P<0.001 vs. placebo Puntuación media de la interferencia del sueño *** *** *** *** *** *** ** ** *** This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of painful diabetic peripheral neuropathy (DPN) (study 131). Patients were randomized to, and treated with, LYRICA 300 mg/day (n=76) or placebo (n=70), taken in a TID (three times daily) dosing schedule. Patients in the LYRICA group received 300 mg/day from the start of the study. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The mean end point pain-related sleep interference score (a measure of the extent to which pain disturbed sleep) in each LYRICA group was compared with placebo. Mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate sleep interference at baseline (mean sleep interference score was across both groups). LYRICA 300 mg/day was significantly more effective than placebo in improving pain-related sleep interference as early as week 1, and for the duration of the 8-week study Reference Rosenstock et al. Pain.2004;110:628-38 Additional key words: diabetes, diabetic, rapid, sustained Final Semana Rosenstock et al. Pain.2004;110:628-38

Pregabalina en neuropatía diabética periférica : Mejoría rápida del dolor y en la interferencia del sueño relacionada con el dolor Dolor Interferencia del sueño *P<0.01 vs. placebo *P<0.01 vs. placebo Puntuación media Puntuación media * * * * * * * * * * * * * * * * * * This slide presents data from an 8-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in the treatment of painful diabetic peripheral neuropathy (DPN) (study 131). Patients were randomized to, and treated with, LYRICA 300 mg/day (n=76) or placebo (n=70), taken in a TID (three times daily) dosing schedule. Patients in the LYRICA group received 300 mg/day from the start of the study. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly and end point pain and sleep interference scores (a measure of the extent to which pain disturbed sleep) in the LYRICA group were compared with placebo. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean pain score was across both groups). Patients had moderate sleep interference at baseline (mean sleep interference score was across both groups). LYRICA 300 mg/day was significantly more effective in improving pain than placebo as early as week 1 and for the duration of the 8-week study. LYRICA 300 mg/day was significantly more effective than placebo in improving pain-related sleep interference as early as week 1, and for the duration of the 8-week study Reference Rosenstock et al. Pain.2004;110:628-38 Additional key words: diabetes, diabetic, rapid, sustained Final Final Semana Semana Pregabalina 300 mg/día (n = 76) Rosenstock et al. Pain.2004;110:628-38

Resultados del estudio clave de dosis flexible en neuropatía diabética periférica/neuralgia posherpética

Estudio de dosis flexible en neuropatía diabética periférica/neuralgia posherpética: antecedentes
Tratamiento del estudio 2 brazos de dosis de pregabalina frente a placebo Dosis fija de 600 mg/día Dosis flexible de mg/día (inicio con 150 mg, ajuste semanal en la dosis) 12 semanas, a doble ciego, aleatorizado Dosificación BID con una fase de dosis flexible de 4 semanas en un brazo Pacientes con neuropatía diabética periférica/neuralgia posherpética No se permitieron analgésicos concomitantes Características del período inicial Total aleatorizado y tratados n = 329 (~70% con neuropatía diabética periférica y ~30% con neuralgia posherpética) 54% de hombres, edad media = 62 años (26-87) Puntuación media del dolor en el período inicial (SD) = 6.7 (1.6); neuropatía diabética periférica y neuralgia posherpética similares This slide describes the background and baseline characteristics in a 12-week, randomized, double-blind study in the treatment of neuropathic pain (~70% with DPN and ~30% with PHN), taken in a BID (twice daily) dosing schedule (study 155). Patients were randomized to, and treated with, either flexible-dose LYRICA (pregabalin) mg/day (n=139), fixed-dose LYRICA 600 mg/day (n=128) or placebo (n=62), taken in a BID dosing schedule. Patients randomized to fixed-dose LYRICA 600 mg/day received 300 mg/day for the first week then 600 mg/day for the 11 weeks thereafter. Patients randomized to flexible-dose LYRICA mg/day received 150 mg/day for the first week and doses could be escalated to 300, 450 and 600 mg/day at 150 mg/week intervals based on patients’ clinical response (i.e. 4-week dose-adjustment period to maximum LYRICA dose). Only one downward dose adjustment was permitted to manage adverse events. The key talking points for this slide are as follows: Patients with creatinine clearance (CLcr) <60mL/min were excluded, as LYRICA is renally excreted and dosage adjustment is required in renal impairment. Of the the 249 patients with DPN, 83% had Type II diabetes and the mean duration of DPN was 4.8 years. Of the 89 patients with PHN, the mean duration of PHN was 3 years. Mean baseline pain scores were similar in patients with DPN (~6.7) and PHN (~7.1). Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic Data on file, Pfizer Inc

Período inicialde 1 semana Dosis de mantenimiento
Estudio de dosis flexible en neuropatía diabética periférica/neuralgia posherpética: Diseño 12 semanas a doble ciego Período inicialde 1 semana Aleatorización 0 – 1 Semana dosis en escala Dosis flexible 1-4 semanas Dosis de mantenimiento 5-12 semanas PGB 600 mg/día PGB 300 mg/día PGB 600 mg/día PGB 450 mg/día PGB 300 mg/día This slide shows the design of a 12-week, randomized, double-blind study in which patients (~70% with DPN and ~30% with PHN), were randomized to, and treated with, either flexible-dose LYRICA (pregabalin) mg/day (n=139), fixed-dose LYRICA 600 mg/day (n=128) or placebo (n=62), taken in a BID (twice daily) dosing schedule (study 155). The key talking points for this slide are as follows: Randomization in this study was 2:2:1(placebo) unlike other studies, and gabapentin non-responders were allowed to enter this study. Patients randomized to fixed-dose LYRICA 600 mg/day received 300 mg/day for the first week then 600 mg/day for the 11 weeks thereafter. Patients randomized to flexible-dose LYRICA mg/day received 150 mg/day for the first week and doses could be escalated to 300, 450 and 600 mg/day at 150 mg/week intervals based on patients’ clinical response (i.e. 4-week dose-adjustment period to maximum LYRICA dose). Only one downward dose adjustment was permitted to manage adverse events. The average LYRICA dose in the flexible dosing group from weeks 5-12, during which time the selected dose was maintained (after minimum 4 weeks to adjust to 600 mg/day if needed), was 457 mg/day. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic PGB 150 mg/día Placebo Semana 0 Semana 4 Semana 12 Tiempo Data on file, Pfizer Inc

Estudio de dosis flexible en neuropatía diabética periférica/ neuralgia posherpética: Mejoría del dolor similar en ambos regímenes de dosificación Pregabalina 150 – 600 mg/día (n = 139) Pregabalina 600 mg/día (n = 128) Puntuación media del dolor * * **P<0.01 * * ***P<0.001 * * * * * * This slide presents data from the 12-week, randomized, double-blind, placebo-controlled, study of LYRICA (pregabalin) in neuropathic pain (DPN and PHN) (study 155). Patients were randomized to, and treated with, either flexible-dose LYRICA mg/day (n=139), fixed-dose LYRICA 600 mg/day (n=128) or placebo (n=62), taken in a BID (twice daily) dosing schedule. Patients randomized to fixed-dose LYRICA 600 mg/day received 300 mg/day for the first week then 600 mg/day for the 11 weeks thereafter. Patients randomized to flexible-dose LYRICA mg/day received 150 mg/day for the first week and doses could be escalated to 300, 450 and 600 mg/day at 150 mg/week intervals based on patients’ clinical response (i.e. 4-week dose-adjustment period to maximum LYRICA dose). Only one downward dose adjustment was permitted to manage adverse events. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly scores were also compared. To simplify the slide all P values in the OC analysis from weeks 1 to 12 have been shown as P<0.05; however, at some points, P values were lower (i.e. P<0.01). The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean score 6.7). Flexible-dose LYRICA mg/day and fixed-dose LYRICA 600 mg/day were both significantly more effective in improving pain at end point than placebo. LYRICA 600 mg/day was significantly more effective than placebo as early as week 1, and for the duration of the 12-week study. LYRICA mg/day was not significantly more effective than placebo at week 1 (when all patients were on 150 mg/day before they could be escalated to 300 mg/day), but thereafter, the pain improvement was significantly greater than placebo for the duration of the study. These data indicate that LYRICA is highly effective in the treatment of pain when dosed flexibly. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic, rapid, sustained * * * * * * * * * * * * * *P< mg/día *P< mg/día vs. placebo Final Semana Data on file, Pfizer Inc

Estudio de dosis flexible en neuropatía diabética periférica/ neuralgia posherpética: mejoría rápida y sostenida del dolor Pregabalina 150 – 600 mg/día (n = 139) Pregabalina 600 mg/día (n = 128) * Cambio medio en la puntuación del dolor * * * * * * This slide presents data from the 12-week, randomized, double-blind, placebo-controlled, study of LYRICA (pregabalin) in neuropathic pain (DPN and PHN) (study 155). Patients were randomized to, and treated with, either flexible-dose LYRICA mg/day (n=139), fixed-dose LYRICA 600 mg/day (n=128) or placebo (n=62), taken in a BID (twice daily) dosing schedule. Patients randomized to fixed-dose LYRICA 600 mg/day received 300 mg/day for the first week then 600 mg/day for the 11 weeks thereafter. Patients randomized to flexible-dose LYRICA mg/day received 150 mg/day for the first week and doses could be escalated to 300, 450 and 600 mg/day at 150 mg/week intervals based on patients’ clinical response (i.e. 4-week dose-adjustment period to maximum LYRICA dose). Only one downward dose adjustment was permitted to manage adverse events. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly scores were also compared. This slide shows mean change from baseline throughout the study. To simplify the slide all P values in the OC analysis from weeks 1 to 12 have been shown as P<0.05; however, at some points, P values were lower (i.e. P<0.01). The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean score 6.7). LYRICA 600 mg/day was significantly more effective than placebo as early as week 1, and for the duration of the 12-week study. LYRICA mg/day was not significantly more effective than placebo at week 1 (when all patients were on 150 mg/day before they could be escalated to 300 mg/day), but thereafter, the pain improvement was significantly greater than placebo for the duration of the 12-week study. These data indicate that LYRICA is highly effective in the treatment of pain when dosed flexibly. Reference Data on file, Pfizer Inc, New York, NY, USA . Additional key words: diabetes, diabetic, postherpetic, rapid, sustained * * * * * * * * * * * * * * * * Semana *P< mg/día *P< mg/día vs. placebo La puntuación media del dolor en el periodo inicial fue 6.7 Data on file, Pfizer Inc

*P<0.05 150-600 mg/día, *P<0.05 600 mg/día vs. placebo
Estudio de dosis flexible en neuropatía diabética periférica/neuralgia posherpética: reducción rápida y significativa en la interferencia del sueño relacionada con el dolor Pregabalina 150 – 600 mg/día (n = 139) Pregabalina 600 mg/día (n = 128) *P< mg/día, *P< mg/día vs. placebo Puntuación media en la interferencia del sueño * * * * * * * * * * ***P< ambas dosis * * * * * * * * This slide presents data from the 12-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in neuropathic pain (DPN and PHN) (study 155). Patients were randomized to, and treated with, either flexible-dose LYRICA mg/day (n= 139), fixed-dose LYRICA 600 mg/day (n=128) or placebo (n=62), taken in a BID (twice daily) dosing schedule. Patients randomized to fixed-dose LYRICA 600 mg/day received 300 mg/day for the first week then 600 mg/day for the 11 weeks thereafter. Patients randomized to flexible-dose LYRICA mg/day received 150 mg/day for the first week and doses could be escalated to 300, 450 and 600 mg/day at 150 mg/week intervals based on patients’ clinical response (i.e. 4-week dose-adjustment period to maximum LYRICA dose). Only one downward dose adjustment was permitted to manage adverse events. The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The mean end point pain-related sleep interference score (a measure of the extent to which pain disturbed sleep) in each LYRICA group was compared with placebo. Mean weekly scores were also compared. The key talking points for this slide are as follows: Patients had moderate sleep interference at baseline (mean sleep interference scores across groups range from ). Flexible-dose LYRICA mg/day and fixed-dose LYRICA 600 mg/day were both significantly more effective in improving pain-related sleep interference at end point than placebo. These data indicate that LYRICA significantly improves pain-related sleep interference when dosed flexibly. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic, rapid, sustained Final Semana Data on file, Pfizer Inc

Estudio de dosis flexible en neuropatía diabética periférica/ neuralgia posherpética: reducción rápida y significativa del dolor e interferencia del sueño relacionada con el dolor Dolor Interferencia del sueño Puntuación media * Puntuación media * * * * * * * * * * * * * * * * * * * * * * * * Final Final This slide presents data from the 12-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in neuropathic pain (DPN and PHN) (study 155). Patients were randomized to, and treated with, either flexible-dose LYRICA mg/day (n= 139), fixed-dose LYRICA 600 mg/day (n=128) or placebo (n=62), taken in a BID (twice daily) dosing schedule. Patients randomized to fixed-dose LYRICA 600 mg/day received 300 mg/day for the first week then 600 mg/day for the 11 weeks thereafter. Patients randomized to flexible-dose LYRICA mg/day received 150 mg/day for the first week and doses could be escalated to 300, 450 and 600 mg/day at 150 mg/week intervals based on patients’ clinical response (i.e. 4-week dose-adjustment period to maximum LYRICA dose). Only one downward dose adjustment was permitted to manage adverse events The patient numbers shown on the slide refer to the number of patients included in the primary intention to treat (ITT), last observation carried forward (LOCF) analysis at end point. Changes over time are based on observed case analysis (OC). The primary efficacy variable was, for all pain studies, the mean end point pain score in each LYRICA group compared with placebo, based on pain scores from the last 7 days’ diary entries while patients were on treatment. The mean weekly and end point pain and sleep interference scores were also compared. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean score 6.7). Patients had moderate sleep interference at baseline (mean sleep interference scores across groups range from ). Flexible-dose LYRICA mg/day and fixed-dose LYRICA 600 mg/day were both significantly more effective in improving pain at end point than placebo. LYRICA mg/day was not significantly more effective than placebo in the treatment of pain at week 1 (when all patients were on 150 mg/day before they could be escalated to 300 mg/day), but thereafter, the pain improvement was significantly greater than placebo for the duration of the 12-week study. LYRICA 600 mg/day was significantly more effective than placebo as early as week 1, and for the duration of the 12-week study. Flexible-dose LYRICA mg/day and fixed-dose LYRICA 600 mg/day were both significantly more effective in improving pain-related sleep interference at end point than placebo. These data indicate that LYRICA is highly effective in the treatment of pain and pain-related sleep interference when dosed flexibly. Reference: Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic, rapid, sustained Semana Semana Placebo (n=62) Pregabalina 150 – 600 mg/día (n = 139) Pregabalin mg/day (n=139) Pregabalina 600 mg/día (n = 128) Pregabalin 600 mg/day (n=128) * P< mg/día vs. placebo * P< y 600 mg/día vs. placebo Data on file, Pfizer Inc

Estudio de dosis flexible en neuropatía diabética periférica/ neuralgia posherpética: tasas de los que respondieron (50% de reducción del dolor)* *** *** P<.001 vs. placebo *** 52% 48% % de pacientes 24% This slide presents data from the 12-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in neuropathic pain (DPN and PHN) (study 155). Patients were randomized to, and treated with, either flexible-dose LYRICA mg/day (n= 139), fixed-dose LYRICA 600 mg/day (n=128) or placebo (n=62), taken in a BID (twice daily) dosing schedule. Patients randomized to fixed-dose LYRICA 600 mg/day received 300 mg/day for the first week then 600 mg/day for the 11 weeks thereafter. Patients randomized to flexible-dose LYRICA mg/day received 150 mg/day for the first week and doses could be escalated to 300, 450 and 600 mg/day at 150 mg/week intervals based on patients’ clinical response (i.e. 4-week dose-adjustment period to maximum LYRICA dose). Only one downward dose adjustment was permitted to manage adverse events. Response rates were defined as the proportion of patients with a 30% and a 50% reduction in their pain score from baseline to end point; these were compared between each LYRICA group and the placebo group. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean score 6.7). The 50% responder rates are presented on this slide. A ≥30% reduction in the pain score has previously been shown to be clinically important (Farrar et al. 2001); a ≥50% reduction is accepted to be clinically significant and is often used to compare treatment responses for different agents across clinical trials. Approximately half the patients on flexible-dose LYRICA mg/day (48%) and on fixed-dose LYRICA 600 mg/day (52%) had 50% reduction in their pain score, significantly more than in the placebo group (24%). These data indicate that LYRICA is highly effective in the treatment of pain when dosed flexibly. References Data on file, Pfizer Inc, New York, NY, USA Farrar et al. Pain 2001;94: Additional key words: diabetes, diabetic, postherpetic Dosis de pregabalina (mg/día) *50% de reducción en la puntuación del dolor desde el período inicial hasta el punto final Data on file, Pfizer Inc

Dosis de pregabalina (mg/día) Dosis de pregabalina (mg/día)
Estudio de dosis flexible en neuropatía diabética periférica/ neuralgia posherpética: 50% y 30% de respuesta a reducción del dolor* Respuesta (50%) Respuesta (30%) *** P<0.001 vs. placebo ** P<0.01 vs. placebo ** ** 66% *** 59% *** 52% 48% % de pacientes % de pacientes 37% 24% This slide presents data from the 12-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in neuropathic pain (DPN and PHN) (study 155). Patients were randomized to, and treated with, either flexible-dose LYRICA mg/day (n= 139), fixed-dose LYRICA 600 mg/day (n=128) or placebo (n=62), taken in a BID (twice daily) dosing schedule. Patients randomized to fixed-dose LYRICA 600 mg/day received 300 mg/day for the first week then 600 mg/day for the 11 weeks thereafter. Patients randomized to flexible-dose LYRICA mg/day received 150 mg/day for the first week and doses could be escalated to 300, 450 and 600 mg/day at 150 mg/week intervals based on patients’ clinical response (i.e. 4-week dose-adjustment period to maximum LYRICA dose). Only one downward dose adjustment was permitted to manage adverse events. Response rates were defined as the proportion of patients with a 30% and a 50% reduction in their pain score from baseline to end point; these were compared between each LYRICA group and the placebo group. The key talking points for this slide are as follows: Patients had moderate to severe pain at baseline (mean score 6.7). A ≥50% reduction is accepted to be clinically significant and is often used to compare treatment responses for different agents across clinical trials. Approximately half the patients on flexible-dose LYRICA mg/day (48%) and on fixed-dose LYRICA 600 mg/day (52%) had 50% reduction in their pain score, significantly more than in the placebo group (24%). A ≥30% reduction in the pain score has previously been shown to be clinically important (Farrar et al. 2001) Over half the patients on flexible-dose LYRICA mg/day (59%) and two-thirds on on fixed-dose LYRICA 600 mg/day (66%) had 30% reduction in their pain score, significantly more than in the placebo group (37%). These data indicate that LYRICA is highly effective in the treatment of pain when dosed flexibly. Reference Data on file, Pfizer Inc, New York, NY, USA Farrar et al. Pain 2001;94: Additional key words: diabetes, diabetic, postherpetic, responder Dosis de pregabalina (mg/día) Dosis de pregabalina (mg/día) * Reducción  50% y 30% en la puntuación del dolor desde el período inicial hasta punto final Data on file, Pfizer Inc

Estudio de dosis flexible en neuropatía diabética periférica/ neuralgia posherpética: Mejoría reportada por los pacientes Cambio en la impresión global del paciente (PGIC)* Peor Peor Ningún cambio Mejorado *** ** **P<0.01, ***P<0.001 vs. placebo % de pacientes This slide presents data from the 12-week, randomized, double-blind, placebo-controlled study of LYRICA (pregabalin) in neuropathic pain (DPN and PHN) (study 155). Patients were randomized to, and treated with, either flexible-dose LYRICA mg/day (n= 139), fixed-dose LYRICA 600 mg/day (n=128) or placebo (n=62), taken in a BID (twice daily) dosing schedule. Patients randomized to fixed-dose LYRICA 600 mg/day received 300 mg/day for the first week then 600 mg/day for the 11 weeks thereafter. Patients randomized to flexible-dose LYRICA mg/day received 150 mg/day for the first week and doses could be escalated to 300, 450 and 600 mg/day at 150 mg/week intervals based on patients’ clinical response (i.e. 4-week dose-adjustment period to maximum LYRICA dose). Only one downward dose adjustment was permitted to manage adverse events. Patients rated their global impression of change (PGIC) at end point (compared with baseline) on a 7-point categorical scale from 1=very much improved to 7=very much worse. Results were grouped according to if patients were worse, had no change or were improved at end point. Only those patients who had an end point assessment (upon discontinuation or completion) could be included in this analysis. As some patients did not complete their PGIC questionnaire, the patient numbers in this analysis are slightly lower than in the primary analysis, which was based on daily pain diaries (earlier slide). The analysis tested the significance of the difference between each LYRICA group and the placebo group in the overall distribution of PGIC scores at end point. i.e. not any single PGIC category between LYRICA and placebo, but the relative distribution of categories in each treatment group. The key talking points for this slide are as follows: The proportion of patients that improved was similar in both LYRICA treatment groups. Almost three-quarters of patients on LYRICA 600 mg/day (74%) and on flexible-dose LYRICA mg/day (71%) rated themselves as improved at end point. This was significantly higher than the proportion who were improved in the placebo group (47%). Few patients deteriorated (got worse) on LYRICA (9% on mg/day, 13% on 600 mg/day) compared with placebo (17%). These data indicate that LYRICA is significantly superior to placebo when dosed flexibly. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic Dosis de pregabalina (mg/día) *Medido en una escala de 7 puntos, condensada a 3 categorías Data on file, Pfizer Inc

Puntuación media del dolor
Dosificación BID y TID similarmente efectiva en dolor neuropático periférico Por régimen de dosificación de pregabalina Puntuación media del dolor This slide presents data from 9 completed, fixed-dose studies of LYRICA (pregabalin) in peripheral neuropathic pain (DPN and PHN combined; 5-12 weeks duration). To examine if there were any clinically relevant differences between the TID (three times daily) and BID (twice daily) dosing regimens, the weekly mean pain scores (95% CI) were calculated for pooled 150, 300 and 600 mg/day LYRICA doses according to dosing regimen up to week 5. Of the 810 patients in the pooled TID LYRICA dosing group, 30% were on 150 mg/day, 32% on 300 mg/day and 38% on 600 mg/day. Of the 563 patients in the BID LYRICA dose group pooled, 33% were on 150 mg/day, 41% on 300 mg/day and 26% on 600 mg/day. Thus, the distribution of fixed pregabalin doses within the TID and BID groups was similar. As the shortest study was 5 weeks long, scores were only examined from weeks 1 to 5, and thus all patients from all studies could be included in the analysis up to 5 weeks. The key talking points for this slide are as follows: For each of the three LYRICA fixed doses (150, 300 and 600 mg/day) there were no clinically relevant differences between BID and TID dosing regimens in weekly mean pain scores (data not shown on this slide). In the analysis of all doses pooled, as shown on the slide, the overlapping confidence intervals demonstrate that there are no clinically relevant differences between BID and TID dosing. These data indicate that BID dosing is as effective as TID dosing across the therapeutic dose range ( mg/day). LYRICA may be administered BID (twice daily). TID (three times daily) dosing is possible, offering additional flexibility if needed. Reference Data on file, Pfizer Inc, New York, NY, USA Semana BID = dos veces al día; TID = tres veces al día Data on file, Pfizer Inc

Eficacia de la pregabalina en el dolor neuropático periférico
Resultados a largo plazo de los estudios de extensión de diseño abierto

Estudios de extensión de diseño abierto en neuropatía diabética periférica/ neuralgia posherpética
Extensión de diseño abierto donde ingresaron: 80% (1233/150) tratados con pregabalina a doble ciego 82% (632/775) tratados con placebo a doble ciego Pacientes que completaron la VAS de la SF-MPQ del dolor a intervalos regulares Dosificación flexible de pregabalina permitida; mg/día La dosis más comúnmente seleccionada fue de aproximadamente 300 mg/día La dosis media aproximada fue de 420 mg/día en pacientes tratados por ≥60 semanas (n = 656) This slide outlines some of the background to the open-label extension studies conducted with LYRICA (pregabalin) in the treatment of neuropathic pain (DPN and PHN). Patients were eligible to enter the open-label extension studies if they had participated in double-blind studies and wished to continue on or initiate LYRICA treatment. In these studies, flexible LYRICA dosing was allowed and doses could be adjusted within the dose range of mg/day (based on response to treatment and tolerability) throughout the studies. Although the main objective of these studies was to assess the safety profile of LYRICA with long-term exposure, long-term efficacy data were also collected using the Short-Form McGill (SF-MPQ) pain questionnaire VAS scale data. A fixed date for data cut-off was set (14 February 2003) for the analysis of the SF-MPQ data so that the data could be provided to regulatory authorities. By the data cut-off date, 8.9% of patients had discontinued from these extension studies due to a lack of efficacy and 15.5% of patients had discontinued due to adverse events. The key talking points for this slide are as follows: Substantial proportions (~80%) of patients who had received placebo (632/775) and LYRICA (1233/1550) in 9 double-blind, fixed-dose studies elected to participate in the open-label extension studies. The SF-MPQ pain VAS was completed at regularly scheduled clinic visits (1-6 monthly intervals. The most commonly selected LYRICA dose was approximately 300 mg/day. The mean dose used in patients receiving LYRICA treatment for 60 weeks or more was approximately 420 mg/day. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic

Dosificación en el dolor neuropático periférico Estudios de extensión de diseño abierto*
En general la dosis de pregabalina seleccionada más comúnmente fue de aproximadamente 300 mg/día Ajuste en la dosis (día ) Período (día) 1er trimestre (61–150) 2do trimestre (151–240) 3er trimestre (241–330) 4to (331–420) Media (SD) (141.5) (155.7) (155.3) (156.2) (156.3) Mediana 337 400 405 411 This slide shows LYRICA (pregabalin) dosing data from the 656 patients who received LYRICA for at least 60 weeks (420 days) in open-label extension studies in neuropathic pain (DPN and PHN). Patients were eligible to enter the open-label extension studies if they had participated in double-blind studies and wished to continue on, or initiate, LYRICA treatment. In these studies, flexible LYRICA dosing was allowed and doses could be adjusted within the dose range of mg/day (based on response to treatment and tolerability) throughout the studies. In this analysis of dosing over time, a 60-day ‘dose optimization’ interval was undertaken. Thereafter, the subsequent 1-year period was divided into 90-day increments, and median and mean doses were calculated for each interval. Although these time periods were arbitrary, the aim was to examine dosing data in a group of patients over a long duration of treatment. The key talking points for this slide are as follows: A high proportion (~80%) of patients who had received placebo (632/775) and LYRICA (1233/1550) in the 9 double-blind, fixed-dose studies elected to participate in the open-label extension studies. At the time of the dosing data analysis, a cohort of 656 of these patients had been treated with LYRICA for at least 420 days. The most commonly selected LYRICA dose was approximately 300 mg/day (mean dose mg/day). No clinically meaningful changes in mean or median doses over time were detected, indicating that effective pain relief is maintained with long-term treatment without dose escalation. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic * Una cohorte de pacientes seguida por lo menos 420 días (n = 656) Data on file, Pfizer Inc

Eficacia de la pregabalina en el dolor neuropático periférico sostenido con el tratamiento a largo plazo* Doble ciego Flexible-dose open-label pregabalin ( mg/day) Dosis flexible de pregabalina de diseño abierto (150 – 600 mg/día)) Puntuación media en VAS de la SF-MPQ del dolor This slide presents long-term treatment data from 217 patients who were treated during open-label extension trials for at least 1 year, following double-blind treatment with either placebo or fixed doses of LYRICA (pregabalin; 150, 300 or 600 mg/day). A fixed date for data cut-off was set (14 February 2003) for the analysis of the SF-MPQ data so that the data could be provided to regulatory authorities. Upon entering the open-label extension phase, all patients received flexible-dose LYRICA mg/day. Patients were asked to evaluate their pain at regular clinic visits using the Short-form McGill Pain Questionnaire (SF-MPQ) pain VAS scale, which provides a rating of pain over the past week. The patient placed a mark across a 100-mm line to indicate the intensity of the pain from left (where 0 mm = no pain) to right (100 mm = worst possible pain). The key talking points for this slide are as follows: The SF-MPQ pain VAS was completed at regularly scheduled clinic visits (1-6 monthly intervals. It should be noted that the data are based on 217 patients who were followed from the end of the double-blind phase for the subsequent year. After the double-blind treatment phase, all patients received LYRICA mg/day. The colored icons and lines identify which fixed-dose treatment patients were assigned to in double-blind studies before receiving open-label LYRICA. Patients who received placebo and LYRICA 150 mg/day during the double-blind phase demonstrated improvement in pain after entering the open-label extension and receiving flexible-dose LYRICA. In patients who received fixed doses of LYRICA 300 and 600 mg/day during double-blind treatment, pain relief was maintained after entering the open-label phase (during which doses may have been increased or decreased depending on patient response and tolerability). Overall, the data for all groups, irrespective of double-blind treatment assignment, during the open-label phase demonstrate that effective pain relief was maintained with long-term treatment and that tolerance did not develop (this is corroborated by data on the previous slide showing dosing with long-term treatment). Reference Data on file, Pfizer Inc, New York, NY, USA . Additional key words: diabetes, diabetic, postherpetic, sustained Doble ciego Final Months Meses Dosis asignadas durante el tratamiento a doble ciego antes de que todos los pacientes recibieran la dosis flexible, pregabalina de diseño abierto Placebo Pregabalina 150 mg/día Pregabalina 300 mg/día Pregabalina 600 mg/día *Pacientes tratados por lo menos 1 año (n=217) Data on file, Pfizer Inc

Eficacia de pregabalina en el dolor neuropático periférico: Conclusiones
Eficacia de la pregabalina demostrada en 8 estudios a doble ciego Rango de dosis terapéutica de mg/día Reducción significativa del dolor tan pronto como en una semana y sostenida durante el curso del tratamiento Mejoría clínicamente significativa Tasas altas de los que respondieron a través de los estudios clínicos Eficacia sostenida a largo plazo en estudios de diseño abierto ≥ 1 año Reducción significativa en la interferencia del sueño relacionada con el dolor tan pronto como en una semana Los pacientes reportaron una mejoría general significativa en la Impresión Global de Cambio del Paciente (PGIC) The efficacy and safety of LYRICA (pregabalin) in the treatment of neuropathic pain has been evaluated in an unprecedented clinical development program. Efficacy data are available from 10 completed, randomized, double-blind, controlled studies that included 2750 patients with PHN and DPN. In these studies, LYRICA mg/day provided rapid and sustained relief of peripheral neuropathic pain, significant reductions in pain-related sleep interference, and overall improvements in Patient Global Impression of Change (PGIC). The key talking points for this slide are as follows: LYRICA was statistically superior to placebo (based on primary pain end point) in 8 of the 10 completed studies. The LYRICA therapeutic dose range is mg/day. In the treatment of both PHN and DPN, LYRICA produced significant reductions in pain as early as week 1. Continued improvements were observed over time. Pain reductions were maintained for the duration of double-blind studies (up to 13 weeks) and for at least 1 year in open-label extension studies. A 2-point or ≥30% reduction in the pain score has previously been shown to be a clinically important improvement (Farrar et al. 2001). A clinically important improvement in pain was seen within 1-2 weeks of LYRICA treatment initiation. A ≥50% reduction is accepted to be clinically significant and is often used to compare treatment responses for different agents across clinical trial. Across the 10 neuropathic pain studies, approximately 50% of patients who received LYRICA reported 50% reduction in pain scores. Reductions in pain with LYRICA treatment were accompanied by improvements in pain-related sleep interference. Up to 80% of LYRICA-treated patients rated their overall status (PGIC) as being improved compared with <10% of placebo-treated patients. The results from all studies indicate that LYRICA mg/day is the effective dose range for the treatment of peripheral neuropathic pain. References Data on file, Pfizer Inc, New York, NY, USA Farrar et al. Pain 2001;94: Additional key words: diabetes, diabetic, postherpetic

Tolerabilidad y seguridad de pregabalina en el dolor neuropático periférico: contenido
Revisión de los estudios incluidos en el análisis combinado de tolerabilidad Eventos adversos más frecuentes y suspensiones debido a eventos adversos en los estudios de dolor neuropático periférico Eventos adversos más frecuentes en la base de datos completa a través de las indicaciones Conclusiones This slide provide a brief overview of data and information on LYRICA (pregabalin) tolerability and safety presented in subsequent slides.

Estudios a doble ciego, controlados en el análisis combinado de tolerabilidad: Revisión
Información de 10 estudios del dolor neuropático controlados con placebo 6 neuropatía diabética periférica: duración 5-12 semanas 4 neuralgia postherpética: duración 5-12 semanas Fecha fija de corte para la inclusión de la información en la base de datos combinada, 28 de junio del 2002 Estudios completados recientemente no incluidos: estudios en neuralgia postherpética de 13 semanas y 12 semanas en neuralgia postherpética / neuropatía diabética periférica Rango de dosis terapéutica: pregabalina en dosis de 150, 300 y 600 mg/día Eventos adversos emergentes del tratamiento observados o reportados espontáneamente This slide outlines the pooled neuropathic pain adverse events database for LYRICA (pregabalin; 6 DPN studies 014, 029, 040, 131, 149, 173 and 4 PHN studies 030, 045, 127, 132). All safety data available at cut-off date, 28 June 2002, were included in the safety analysis. Two studies, 173 and 132, were terminated before completion but were included in the pooled safety database (but not in the efficacy database). Two studies included in the pooled efficacy analysis (196 PHN and 155 PHN/DPN) were not included in the safety database as data were not available at the time of the cut-off date. Data from these studies will be included in subsequent updates of the safety database. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic, tolerability Data on file, Pfizer Inc

Tasas bajas de suspensión entre los estudios de dolor neuropático periférico
Total Evento adverso Pregabalina (n = 1556) Falta de eficacia Sin cumplimiento This slide summarizes the discontinuation rates, across the 10 fixed-dose neuropathic pain studies included in the pooled safety analysis database (studies of 5-12 weeks duration). The studies in the pooled neuropathic pain adverse events database for LYRICA (pregabalin) were 014, 029, 040, 131, 149, 173 (DPN) and 030, 045, 127, 132 (PHN). All safety data available at cut-off date, 28 June 2002, were included in the safety analysis. Two studies, 173 and 132, were terminated before completion but were included in the pooled safety database (but not in the efficacy database). Two studies included in the pooled efficacy analysis (196 PHN and 155 PHN/DPN) were not included in the safety database as data were not available at the time of the cut-off date. Placebo (n=764) LYRICA (n=1556) Total 24.2% % Adverse event 5.0% % Lack of efficacy 6.0% % Non-compliance 0.8% % Other 12.4% % The key talking points for this slide are as follows: Discontinuation rates were pooled across the 10 studies. “Other” includes administrative reasons and non-compliance. Overall discontinuation rates were low in the LYRICA and placebo groups. The discontinuation rate due to lack of efficacy was slightly higher in the placebo group than the LYRICA group, and the discontinuation rate due to adverse events was slightly higher in the LYRICA group than in the placebo group. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic, tolerability Otro % de pacientes suspendidos Data on file, Pfizer Inc

Eventos adversos‡ más frecuentes en estudios de dolor neuropático periférico (% de pacientes)
Placebo (n=764) Dosis de pregabalina (mg/día) Todas las dosis de pregabalina combinadas 150 (n=427) 300 (n=509) 600 (n=459) Incidencia (n=1556) Suspensión Mareos 6.4 13.3 25.5 29.6 21.7* 3.1 Somnolencia 3.8 9.8 15.9 17.6 13.8* 2.6 Edema periférico 1.8 5.2 12.0 13.5 9.5* 0.8 Infección 4.8 6.6 7.1 3.9 6.2 0.1 Boca seca 4.7 5.3 8.1 5.9* 0.3 This slide presents pooled data from 10 placebo-controlled studies in neuropathic pain (duration 5-12 weeks). The incidence of all spontaneously reported or observed treatment-emergent adverse events occurring in ≥5% of LYRICA- (pregabalin) treated patients and with higher frequency in the LYRICA group than the placebo group is presented as a percentage of the total number of patients in each group. The incidence of discontinuations associated with these adverse events, in all LYRICA dose groups pooled, is also shown in the far right hand column. The incidence of adverse events in the LYRICA group (all doses pooled) was compared with placebo using the odds ratio or Fisher’s Exact test. P<0.05 indicates LYRICA was statistically significantly different from placebo. Note: Specific data on the subtherapeutic 75 mg fixed dose (n=161) are not shown on the slide, but are included in the all pregabalin doses pooled group. The key talking points for this slide are as follows: LYRICA was well tolerated and the overall discontinuation rate due to adverse events was low (10.8% for LYRICA vs. 5.1% for placebo). Most adverse events were mild or moderate in intensity (only 9.7% severe with LYRICA and 7.1% severe with placebo). The most frequent adverse events tended to be dose-related. The exception was infection which was not significantly different in the LYRICA and placebo groups. Dizziness and somnolence were the most common adverse events reported in the pooled database (and in most of the individual studies). These adverse events tended to be dose-related. Weight gain was an infrequently reported adverse event, but may be observed in some patients in the clinic. Thus additional information is included in these notes. Weight gain was reported as an adverse event in 0.4% on placebo and 3.7% on pregabalin. Only 2 patients (0.1%) discontinued pregabalin due to weight gain. Mean weight change was +0.3 kg on placebo and +1.5 kg on pregabalin. Additional information on some specific adverse events is provided on subsequent slides (dizziness, somnolence, peripheral edema and weight gain). Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic, tolerability ‡ Aquellos que ocurrieron en ≥5% de los paciente tratados con pregabalina y con una frecuencia más alta con pregabalina que con placebo Data on file, Pfizer Inc * P<0.05 todos de pregabalina frente a placebo

Eventos adversos‡ más frecuentes y suspensiones en los estudios de dolor neuropático periférico (% de pacientes) Placebo (n=764) Pregabalina (n=1556) Incidencia Suspendieron Mareos 6.4 0.3 21.7* 3.1 Somnolencia 3.8 0.1 13.8* 2.6 Edema periférico 1.8 9.5* 0.8 Infección 4.8 6.2 Boca seca 5.9* This slide presents pooled data from 10 placebo-controlled studies in neuropathic pain (duration 5-12 weeks). The incidence of all spontaneously reported or observed treatment-emergent adverse events occurring in >5% of LYRICA- (pregabalin) treated patients and with higher frequency in the LYRICA group than the placebo group is presented as a percentage of the total number of patients in each group. The incidence of discontinuations associated with these adverse events is also shown. The incidence of adverse events in the LYRICA group (all doses pooled) was compared with placebo using the odds ratio or Fisher’s Exact test. P<0.05 indicates LYRICA was statistically significantly different from placebo. The key talking points for this slide are as follows: LYRICA was well tolerated and the overall discontinuation rate due to adverse events was low (10.8% for LYRICA vs. 5.1% for placebo). Most adverse events were mild or moderate in intensity (only 9.7% severe with LYRICA and 7.1% severe with placebo). Dizziness and somnolence were the most common adverse events reported in the pooled database, but infrequently resulted in discontinuation. These adverse events were dose-related and tended to occur upon initiation of treatment and resolve on treatment (see late slide). Weight gain was an infrequently reported adverse event, but may be observed in some patients in the clinic. Thus additional information is included in these notes. Weight gain was reported as an adverse event in 0.4% on placebo and 3.7% on pregabalin. Only 2 patients (0.1%) discontinued pregabalin due to weight gain. Mean weight change was +0.3 kg on placebo and +1.5 kg on pregabalin. Additional information on some specific adverse events is provided on subsequent slides (dizziness, somnolence, peripheral edema and weight gain). Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic, tolerability * P<0.05 todos de pregabalina frente a placebo ‡ Aquellos que ocurrieron en ≥5% de los pacientes tratados con pregabalina y con una frecuencia más alta con pregabalina que con placebo Data on file, Pfizer Inc

Tasa baja de suspensión debido a eventos adversos‡ más frecuentes en los estudios de dolor neuropático periférico (% de pacientes) Placebo (n=764) Dosis de pregabalina (mg/día) 150 (n=427) 300 (n=509) 600 (n=459) Todos (n=1556) Mareos 0.3 2.3 2.6 5.7 3.1 Somnolencia 0.1 1.2 2.8 4.6 Edema periférico edema 0.5 1.1 0.8 Infección 0.2 Boca seca 0.9 This slide presents pooled data from 10 placebo-controlled studies in neuropathic pain (duration 5-12 weeks). The discontinuation rates, by LYRICA (pregabalin) dose, and for all doses pooled, for the most frequent adverse events is presented as a percentage of the total number of patients in each group. Note: Specific data on the subtherapeutic 75 mg fixed dose (n=161) are not split out on this slide, but are included in the all pregabalin doses pooled group. The key talking points for this slide are as follows: LYRICA was well tolerated and the overall discontinuation rate due to adverse events was low (10.8% for LYRICA vs. 5.1% for placebo). The discontinuation rate was low, and dose-related across LYRICA dose groups. Despite the adverse events listed being the most frequently reported, all were associated with a low discontinuation rate. Even at the highest LYRICA dose (600 mg/day), the two most common adverse events, dizziness and somnolence, only resulted in the discontinuation of 5.7% and 4.8% of patients, respectively. Weight gain was an infrequently reported adverse event, but may be observed in some patients in the clinic. Thus additional information is included in these notes. Only two patients (0.1%) with neuropathic pain discontinued LYRICA due to weight gain (both on LYRICA 300 mg/day) Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic, tolerability ‡ Las suspensiones debidas a eventos adversos ocurrieron en >5% de los pacientes tratados con pregabalina y con una frecuencia mayor con pregabalina que con placebo Data on file, Pfizer Inc

Eventos adversos más frecuentes en todos los ensayos controlados‡ (% de pacientes)
Placebo (n=2290) Dosis de pregabalina (mg/día) Todas las dosis combinadas de pregabalina 150 (n=1077) 300 (n=1100) 600 (n=1738) Incidencia (n=5232) Suspensión Mareos 8.7 15.1 30.0 35.6 29.1* 4.0 Somnolencia 7.8 13.4 21.4 28.3 22.6* 3.5 Boca seca 3.4 5.4 6.9 10.8 9.1* 0.4 Infección 8.0 7.5 6.0 8.1 <0.1 Astenia 5.2 5.8 9.3 7.3* 0.9 Ambliopía 2.1 4.4 9.0 6.5* 0.7 Edema periférico 1.4 3.8 8.3 7.0 5.6* 0.5 Pensamiento anormal 1.6 2.3 2.9 0.8 Aumento de peso 4.7 8.2 0.2 This slide presents the most frequent treatment-emergent adverse events reported during all 29 controlled LYRICA (pregabalin) trials across all indications studied (pain, epilepsy and psychiatry). The frequency of adverse events is expressed as a percentage of the total patient number. Adverse events for LYRICA fixed doses 150, 300 and 600 mg/day are shown. In addition, the frequency for all LYRICA doses pooled is shown ( mg/day). It should be noted that some trials in indications other than pain employed some other LYRICA doses (200, 400 and 450 mg/day) but these are not split out on the slide. In addition, subtherapeutic doses (<150 mg/day) are not split out on the slide but are included in the all pregabalin doses pooled. Therefore the total patient numbers shown for all LYRICA doses pooled exceeds the sum of the fixed doses shown. The incidence of adverse events in the LYRICA group (all doses pooled) was compared with placebo using the odds ratio or Fisher’s Exact test. P<0.05 indicates LYRICA was statistically significantly different from placebo. The key talking points for this slide are as follows: The overall profile of adverse events, across indications, was similar to the profile in neuropathic pain studies. LYRICA was well tolerated and the overall discontinuation rate due to adverse events was low (13.4% for LYRICA vs. 5.9% for placebo). Dizziness and somnolence were the two most frequent adverse events. They were generally mild or moderate, occurred soon after initiation of treatment (1-2 days), tended to resolve on treatment and infrequently resulted in discontinuation. The remaining seven adverse events also infrequently resulted in discontinuation (<1%). The adverse event, amblyopia, was the term used to classify adverse events that were mainly described by the investigators as blurred/blurry vision. The adverse event, thinking abnormal, was used to classify adverse events reported by investigators such as difficulty with concentration/attention. Serious adverse events (SAEs) were reported in 2.3% of LYRICA-treated (n=5232) and 2.1% of placebo-treated (n=2290) patients in the database of 29 controlled trials across indications. The most common SAEs were accidental injury, chest pain, congestive heart failure, myocardial infarction and pneumonia. Overall, these data demonstrate that LYRICA has a favorable tolerability profile. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: tolerability ‡ Aquellos que ocurrieron en ≥5% de los pacientes tratados con pregabalina y con una frecuencia más alta con pregabalina que con placebo en 29 estudios a través de las indicaciones Data on file, Pfizer Inc * P<0.05 todos de pregabalina frente a placebo

Inicio y resolución de mareo y somnolencia en los ensayos de dolor neuropático periférico
Mareos Somnolencia Incidencia* 21.7% 13.8% Suspensión* 3.1% 2.6% Mediana de tiempo hasta el inicio† 1-2 días Mediana de tiempo hasta la resolución (completaron)† 6-17 días 26-31 días This slide presents some key data to further explain the onset and resolution of the 2 most common adverse events associated with LYRICA (pregabalin), dizziness and somnolence. The data in the table are for all LYRICA doses from 10 pooled controlled studies in neuropathic pain. The day of onset and of resolution was recorded by the investigator on the Case Report Form. Resolution data are only available for those patients who completed the studies, as if patients dropped out of the study (and ceased treatment) there was no way of ascertaining if these adverse events resolved while on treatment. The key talking points for this slide are as follows: Although dizziness and somnolence were the most frequently reported adverse events associated with LYRICA treatment, these events infrequently led to discontinuation from treatment. This indicates that patients tolerate these adverse events. Both occurred very soon after the initiation of treatment. Both dizziness and somnolence resolved in the majority of patients who stayed on treatment, indicating these adverse events do not persist and that patients developed tolerance to them. Of the patients who experience dizziness, 86% remained on LYRICA treatment. Of the patients who experienced somnolence, 81% remained on LYRICA treatment. The data indicate that these adverse events are tolerated by patients and tend to resolve on treatment. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic, tolerability *Todos los grupos de dosis de pregabalina combinados; n=1556 † Mediana de tiempo hasta el inicio y resolución entre los grupos de dosis de 150, 300 y 600 mg/día Data on file, Pfizer Inc

Tolerabilidad en los ancianos en 10 ensayos de dolor neuropático periférico
Pregabalina ha sido bien estudiada en pacientes ancianos Edad media en 10 ensayos = 64 años (rango de 21 a 100 años) Edad media de 72 años en los estudios en neuralgia posherpética 22% de todos los pacientes tenían 75 años La eficacia en los ancianos fue similar a la de los pacientes más jóvenes La pregabalina fue igualmente bien tolerada en los pacientes jóvenes como en los ancianos No se requirió ningún ajuste en la dosificación, excepto en función renal deteriorada This slide summarizes information on adverse events in the elderly reported in the 10 double-blind, controlled neuropathic pain studies included in the safety and tolerability summary. The key talking points for this slide are as follows: In the LYRICA (pregabalin) neuropathic pain clinical development program, a large proportion of patients were over 65 years. The mean age was 64 years. In PHN studies alone the mean age was 72 years. 22% (1 in 5) of patients were 75 years. LYRICA was well tolerated in elderly patients and there is no evidence that the most common adverse events increased in frequency with increasing age. “Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication” (from Summary of Product Characteristics) The prescribing information advises that dizziness and somnolence may increase the occurrence of falls in the elderly, and that care should be taken. The incidence of accidental injury in older patients (≥75 years) who experienced dizziness and somnolence was not significantly greater than among younger patients. The advice to use care in the elderly who might experience dizziness or somnolence was based on usual clinical practice recommendations when using CNS-active drugs in the elderly. LYRICA dosing does not require adjustment in older patients, unless they have renal impairment. Reference Data on file, Pfizer Inc, New York, NY, USA Summary of Product Characteristics: please consult local prescribing information Additional key words: diabetes, diabetic, postherpetic Data on file, Pfizer Inc

Perfil de laboratorio, signos vitales y examen por ECG
Perfil de laboratorio similar a placebo Ningún patrón en anormalidad en laboratorio asociado con la pregabalina Ningún cambio clínicamente relevante en el control de glucosa en neuropatía diabética periférica Ningún cambio clínicamente importante en los signos vitales Presión arterial, frecuencia cardiaca Ningún hallazgo clínicamente importante en el electrocardiograma (ECG) This slide summarizes information from the overall LYRICA (pregabalin) clinical development program. The key talking points for this slide are as follows: LYRICA was not associated with any pattern of clinically relevant laboratory abnormalities (e.g. no transaminase elevation, electrolyte disturbance). LYRICA was not associated with clinically important changes in cardiovascular assessments such as blood pressure (BP) and heart rate (HR). ECGs were performed in several studies and the ECGs were read by an external expert reader. LYRICA was not associated with any clinically significant ECG changes. These data indicate that LYRICA has a favorable safety profile. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: safety Data on file, Pfizer Inc

Tolerabilidad y seguridad: Resumen
La pregabalina es generalmente bien tolerada Tasas bajas de suspensión (10.8% con pregabalina frente a 5.0% con placebo) Bien tolerado en pacientes ancianos La mayoría de los eventos adversos leves o moderados Relacionados con la dosis La mayoría de los eventos adversos afectan el sistema nervioso central Mareos y somnolencia Generalmente transitorios Ninguna preocupación de seguridad especial emergió ECG, signos vitales, pruebas de laboratorio, eventos adversos serios This slide summarizes the conclusions from the evaluation of tolerability and safety in the neuropathic pain studies completed to date. These conclusions are supported by the data previously presented on slides and in the notes. The key talking points for this slide are as follows: LYRICA (pregabalin) has a favorable tolerability and safety profile. Discontinuation due to adverse events was infrequent, despite the fact that many elderly patients were treated in neuropathic pain studies. Adverse events were generally mild or moderate in intensity, and the most frequent adverse events tended to be dose-related. As expected for a CNS-active agent, the most common adverse events associated with LYRICA treatment were dizziness and somnolence. These events tended to occur soon after initiation of treatment and resolved while patients remained on treatment. Very few patients discontinued LYRICA due to these adverse events, further indicating that they are generally well tolerated and do not persist. Extensive safety monitoring was undertaken in the clinical studies and no special safety concerns emerged in the extensive database. Reference Data on file, Pfizer Inc, New York, NY, USA Additional key words: diabetes, diabetic, postherpetic, tolerability, safety Data on file, Pfizer Inc

Indicación y dosificación: dolor neuropático periférico
La pregabalina está indicada para el tratamiento del dolor neuropático periférico en adultos Rango de dosis El rango de dosificación es de 150 a 600 mg por día administrado en dos o tres dosis divididas. La pregabalina puede ser tomada con o sin alimento Dosis en el dolor neuropático periférico El tratamiento de pregabalina puede ser iniciado a una dosis de 150 mg al día Con base en la respuesta individual del paciente y la tolerabilidad, la dosis puede ser aumentada a 300 mg al día después de un intervalo de 3 a 7 días y; En caso necesario, aumentar hasta una dosis máxima de 600 mg por día después de un intervalo adicional de 7 días This slide shows a summary of the approved indication and recommended dosing for LYRICA (pregabalin) in neuropathic pain. The key talking points for this slide are as follows: LYRICA is approved for the treatment of peripheral neuropathic pain in adults, based on clinical trials in patients with PHN and DPN. The recommended LYRICA dose range is mg/day. LYRICA may be administered BID (twice daily). TID (three times daily) dosing is possible, offering additional flexibility if needed. In long-term extension studies, the most commonly selected LYRICA was approximately 300 mg/day. References Data on file, Pfizer Inc, New York, NY, USA Summary of Product Characteristics: please consult local prescribing information Resumen de las características del producto

Dosificación simple de pregabalina en dolor neuropático periférico
Dosificación BID (dos veces al día) La dosis utilizada más a menudo en estudios de diseño abierto fue aproximadamente de 300 mg/día Relación clara de respuesta a la dosis Puede ser tomado con o sin alimento Es necesaria la reducción en la dosificación en pacientes con insuficiencia renal This slide illustrates the simplicity and flexibility associated with using LYRICA (pregabalin) in the treatment of peripheral neuropathic pain. The key talking points for this slide are as follows: LYRICA is approved for the treatment of peripheral neuropathic pain in adults. LYRICA may be administered BID (twice daily). TID (three times daily) dosing is possible, offering additional flexibility if needed. Studies suggest that LYRICA doses are equally effective whether given BID or TID; the BID dose schedule is suggested with the optional flexibility of TID dosing. LYRICA treatment should be started at a dose of 150 mg/day (75 mg BID). Based on individual patient response and tolerability, the dosage may be increased to 300 mg/day (150 mg BID) after an interval of 3 to 7 days, and if needed, to a maximum dose of 600 mg/day (300 mg BID) after an additional 7-day interval. In long-term extension studies, the most commonly selected LYRICA dose was 300 mg/day. A dosage reduction is necessary in patients with renal impairment. References Data on file, Pfizer Inc, New York, NY, USA Summary of Product Characteristics: please consult local prescribing information

FIBROMIALGIA Y PREGABALINA

FIBROMIALGIA Aunque previamente se pensó que era un trastorno musculoesquelético primario, información reciente ha dado evidencia de que la fibromialgia es un padecimiento resultante de un procesamiento desordenado del sistema nervioso central. La FM es un padecimiento subdiagnosticado, pero su prevalencia es de al menos 2%, lo que arrojaría una cifra total de alrededor de 8 millones en EEUU Se piensa que la fibromialgia es producto de cambios neurológicos en la forma en la que los pacientes perciben el dolor, específicamente una elevada sensibilidad a los estímulos que normalmente no son dolorosos.

PREVALENCIA POR SEXO Con respecto al sexo, la Fibromialgia es una patología que afecta masivamente a las mujeres en una proporción que se cifra entre 8/1 y 20/1 (mujeres / hombres), sin que sepamos a qué se debe esta masiva predilección por el sexo femenino. Pese a ello es conveniente recordar que existen hombres con Fibromialgia, pues a veces su diagnóstico se hace más difícil por ésta circunstancia

PUNTOS DOLOROSOS

El Dolor en los relatos de la mujer
“… me duele todo…” “… pero como me ven de pie, suponen que no tengo nada…” “ ...y debo seguir adelante... “ ...y como mis análisis y placas son normales, insisten en que no tengo nada..” “ ...y además me dicen que todo “está en mi cabeza”.... “ ...y debo seguir adelante...” EEUU Interconsulta y Psiquiatría de Enlace Dra Ingrid Brunke 2009 University of North Carolina at Wilmington, EEUU

CRITERIOS DIAGNOSTICOS DE FIBROMIALGIA
Dolor difuso durante más de tres meses, en más de tres localizaciones. Ausencia de signos biológicos, artritis o traumatismos. Cinco o más puntos dolorosos a la palpación. Presencia de 3 o más síntomas menores: ansiedad, alteraciones del sueño, sensación de hinchazón y hormigueo,...)

CARACTERISTICAS fibromialgia se caracteriza por dolor crónico generalizado que puede ser implacable y usualmente está acompañado de sueño deficiente, rigidez (tensión) y fatiga; quienes la padecen también reportan alteraciones en la sensibilidad dolor y malestar de tipo gripal. El dolor de la fibromialgia puede limitar la capacidad de un paciente para trabajar y a menudo da como resultado mayores costos médicos y discapacidad. “Yo tuve que dejar mi carrera y no me fue posible participar en muchas de las actividades de mis hijos”, expresó Carolyn Bishop, una paciente con fibromialgia , quien participó en uno de los estudios clínicos de Pregabalina.

La Fibromialgia es una enfermedad de causa desconocida (como el 67% de todas las enfermedades definidas hoy en día) cuyo síntoma principal es el dolor crónico generalizado que se localiza, esencialmente, en zonas musculares, tendinosas, articulares y viscerales. La Fibromialgia es la causa más frecuente de dolor generalizado y configura un grupo importante y heterogeneo de pacientes, que requiere un enfoque individualizado. En la actualidad, la Fibromialgia se hipotetiza que forma parte de un espectro amplio de síndromes y situaciones clínicas que cursan con procesos de sensibilización e hipersensibilidad central, los llamados "Central Sensitivity Syndromes" El profesional más adecuado para confirmar el diagnóstico de la Fibromialgia es el reumatólogo, pues la fiabilidad diagnóstica del médico de asistencia primaria es baja (una unidad especializada confirmó el diagnóstico sólo en un 68% de los casos), aunque una vez diagnosticada, el seguimiento de los casos no complejos, puede quedar en manos del médico de familia

Aunque su causa, como decimos, es desconocida, cada vez se detectan más evidencias al respecto de una base genética de la Fibromialgia que se expresa ante determinadas circunstancias y que condiciona una respuesta anómala del Sistema Nervioso y una facilidad específica para incrementar los procesos de sensibilización al dolor , al menos en aquellos casos que cursan con una extraordinaria sensibilidad dolorosa ante el tacto, el roce o los estímulos térmicos mínimos (alodinia). El dolor y otros síntomas de la Fibromialgia se autoalimentan con el paso del tiempo, lo que hace especialmente importante un diagnóstico precoz

CARACTERISTICAS Crónica, costosa en su tratamiento
Debilitante, puede llegar a ser invalidante Prevalencia 2% + Población femenina De largo derrotero en la consulta multidisciplinaria: clínicos, reumatólogos, traumatólogos, psiquiatras, etc Colegio Americano de reumatología – 1990 Criterios diagnósticos de Fibromialgia dispareunia Síntomas afectivos Trastornos del sueño Astenia cefalea parestesias 11 de 18 ptos dolorosos positivos Sindromes asociados FIBROMIALGIA PSICOPATOLOGIA Sobreadaptadas Comorbilidad con trastornos de personalidad (narcisista, obsesiva, histriónica,dependiente...)‏ Comorbilidad en eje I fundamentalmente con trastorno adaptativo, trastornos por ansiedad generalizada y distimia, Hipótesis: depresión enmascarada. Situaciones de stress previo desencadenante.

TRATAMIENTO AINES(antiinflamatorios). Antidepresivos.
Relajantes musculares. Fármacos que aumenten el nivel activo de serotonina en el cerebro. Infiltraciones de anestésicos en los puntos dolorosos.

25/06/2007 La FDA ha aprobado el uso de Pregabalina para el tratamiento de la Fibromialgia.
Madrid, 25 de junio de La Food and Drug Administration (FDA) ha dado luz verde al uso de pregabalina para el tratamiento de la fibromialgia, uno de los trastornos de dolor crónico y extendido más comunes en los Estados Unidos. La aprobación de pregabalina, representa un gran paso para aquellas personas que sufren este tipo de síndrome. La FDA no contaba previamente con opciones de tratamiento de esta patología autorizadas. Esta aprobación se ha conseguido gracias en los resultados de un estudio de 14 semanas que incluyó a 745 pacientes con fibromialgia. Los pacientes que fueron tratados con pregabalina en este estudio, redujeron hasta en un 50% o más su dolor, frente a aquellos que recibieron placebo. Igualmente, los pacientes a los que se les administró pregabalina reportaron mejoras significativas en su estado general de salud.

Dolor Neuropatico.

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