CHRONIC NEUROPATHIC PAIN MECHANISMS AND MANAGEMENT

描述(改编自申请者摘要)：Michael Rowbotham，a 临床神经学家和专门研究慢性疼痛的临床神经学家， 在以病人为中心的研究方面享有国际声誉 神经病理性疼痛机制及临床止痛试验。加州大学旧金山分校的疼痛 临床研究中心(PCRC)由罗伯坦博士于1990年创立，是一家 临床研究单位位于大学拥有的空间内，接待NIH， 为探索性临床研究和临床提供私人和行业支持 审判。作为加州大学旧金山分校疼痛机制NINDS项目的PI， 将该计划的四个基本内容的进展转化为临床研究 科学实验室得到了培育。Rowbotham医生指导了15名临床初学者 来自不同背景的科学家在PCRC，并正在开发一种独特的两种 年研究/临床培训计划，将PCRC、 神经学疼痛研究培训助学金与麻醉-疼痛管理 中心联谊会。为期5年的K-24支持将协助罗伯坦博士 实现他长期的职业目标，建立一个综合的临床 研究计划：(1)有全面的疼痛研究培训 初级临床研究人员的课程；(2)进行探索性 不同神经病理性疼痛机制的临床研究 紊乱；(3)使用实验性疼痛模型评估新的止痛药 健康志愿者和患者，(4)将基础科学进步转化为 精心设计的促进疼痛治疗的临床试验；(5)与疼痛有关 阿片类药物敏感性、耐受性和长期疗效的机制。这个 项目I中的实验将：(A)确定阿片类药物不敏感的慢性 痛苦是通过同时测量实验诱导的 疼痛和持续的临床疼痛静脉注射。瑞芬太尼输注；(B)确定 长时间的静脉注射。瑞芬太尼输注可产生急性止痛耐受 实验诱导的疼痛和痛觉过敏以及正在进行的慢性 以及(C)前瞻性评估阿片类止痛剂耐受性的发展。 在长期口服阿片类药物治疗期间。项目II将检验假设 强直性带状疱疹后慢性带状疱疹后遗神经痛的发生 取决于初始神经损伤的严重程度和神经的质量 恢复。对患有急性带状疱疹疼痛的患者进行为期6个月的随访 疼痛强度、情绪、生活质量、痛觉异常、疼痛程度的测量 受影响的皮肤，感觉功能的定量测试，对受控的反应 辣椒素的应用和连续皮肤穿孔活检测量 病变皮肤和正常皮肤的皮肤神经支配。

DESCRIPTION (Adapted From The Applicant's Abstract): Michael Rowbotham, a clinical neurologist and clinical neuroscientist specializing in chronic pain, has an international reputation as a leader in patient-oriented research on neuropathic pain mechanisms and clinical analgesic trials. The UCSF Pain Clinical Research Center (PCRC), started by Dr. Rowbotham in 1990, is a clinical research unit located in University-owned space that receives NIH, private, and industry support for exploratory clinical research and clinical trials. As a PI in the NINDS Program Project on Pain Mechanisms at UCSF, clinical research that translates advances from the Program's four basic science labs is fostered. Dr. Rowbotham has mentored 15 beginning clinical scientists from diverse backgrounds in the PCRC, and is developing a unique two year research/clinical training program that brings together the PCRC, the Neurology Pain Research Training Grant, and the Anesthesia-Pain Management Center Fellowship. K-24 support for a 5 year period will assist Dr. Rowbotham achieve his long-term career goal of establishing an integrated clinical research program that: (1) has a comprehensive pain research training curriculum for beginning clinical investigators; (2) conducts exploratory clinical research on pain mechanisms underlying different neuropathic pain disorders; (3) uses experimental pain models to evaluate new analgesics in healthy volunteers and patients, (4) translates basic science advances into well designed clinical trials to advance pain therapy; (5) relates pain mechanisms to opioid sensitivity, tolerance, and long term efficacy. The experiments in Project I will: (a) determine if opioid-insensitive chronic pains exist by simultaneously measuring the response of experimentally induced pain and ongoing clinical pain to i.v. remifentanil infusion; (b) determine if a prolonged i.v. remifentanil infusion can produce acute analgesic tolerance to both the experimentally induced pain and hyperalgesia and the ongoing chronic pain; and (c) prospectively assess development of opioid analgesic tolerance during long term oral opioid therapy. Project II will test the hypothesis that development of chronic post-herpetic neuralgia after herpes zoster strongly depends on the severity of the initial neural injury and the quality of neural recovery. Patients with acute zoster pain will be followed for 6 months on measures of pain intensity, mood, quality of life, allodynia, extent of affected skin, quantitative tests of sensory function, response to controlled applications of capsaicin, and serial skin punch biopsy measurement of cutaneous innervation in affected and normal skin.