Opioid Responsivity/ Analgesic Tolerance in Chronic Pain

慢性疼痛中的阿片类药物反应/镇痛耐受性

• 批准号: 6565208
• 负责人: MICHAEL C ROWBOTHAM
• 金额: $ 18.85万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6565208
• 关键词: amitriptyline; analgesia; analgesics; chronic pain; clinical research; clinical trials; cutaneous sensory nerve; drug tolerance; endogenous opioid; human subject; hyperalgesia; injection /infusion; morphinans; receptor sensitivity; sensory receptors

DESCRIPTION (Applicant?s abstract): 1. We will test the hypothesis that underlying pain mechanism is a determinant of opioid sensitivity by simultaneously measuring in both neuropathic and non-neuropathic chronic pain patients the response of experimentally induced pain and ongoing clinical pain to I.V. remifentanyl infusion. For experimental pain, we will use a model which combine non-injurious heating and topical capsaicin to produce stable areas of cutaneous secondary hyperalgesia. In health volunteers, this model is opioid responsive. Study 1 is a two session, placebo-controlled study of the effect on experimental and clinical pain of brief infusions of the high efficacy, ultra-short acting opioid remifentanyl in 60 non-opioid using chronic pain patients. 2. In study 2 we will determine whether a prolonged I.V. remifentanyl infusion in opioid-naïve volunteers will produce acute analgesic tolerance to both noxious thermal stimulation and experimentally induced cutaneous secondary hyperalgesia. We will then test patients with ongoing chronic pain. Demonstrating the simultaneous development of acute analgesic tolerance to experimental pain and chronic pain would indicate that analgesic tolerance is possible during long term opioid therapy. If acute tolerance develops, physical dependence in the form of withdrawal symptoms, hyperalgesia to noxious stimuli, and a rebound increase in pain over pretreatment levels may follow the remifentanyl infusion. 3. Analgesic tolerance has been shown to develop during long term opioid therapy of chronic non-malignant pain. In Study 3, non-opioid using chronic pain patients will undergo a placebo-controlled study of the analgesic effect of I.V. remifentanyl on acute experimental and chronic pain before and following a 9 week, randomized parallel design, double-blind trial. Forty subjects will receive the opioid hydromorphone and a control group of 20 will receive the tricyclic antidepressant amitriptyline. At the end of the initial 3 week titration period and again after 6 weeks of fixed dosing, the I.V. remifentanyl infusion will be repeated to reconstruct the dose-response curve for experimental and chronic pain.

描述（申请人的摘要）： 1. 我们将检验以下假设： 潜在的疼痛机制是阿片类药物敏感性的决定因素 同时测量神经性和非神经性慢性疼痛 患者对实验引起的疼痛和持续的临床疼痛的反应 到 I.V.瑞芬太尼输注。对于实验性疼痛，我们将使用一个模型 将无害加热和局部辣椒素结合起来，产生稳定的区域 皮肤继发性痛觉过敏。在健康志愿者中，这个模型是阿片类药物 反应灵敏。研究 1 是一项为期两次的安慰剂对照研究，旨在研究 高效短暂输注的实验和临床疼痛， 超短效阿片类药物瑞芬太尼治疗 60 例非阿片类药物慢性疼痛 患者。 2. 在研究 2 中，我们将确定是否延长 I.V.瑞芬太尼输液 在未使用阿片类药物的志愿者中会对两种药物产生急性镇痛耐受 有害热刺激和实验诱导的皮肤继发性 痛觉过敏。然后我们将对患有持续慢性疼痛的患者进行测试。 证明急性镇痛耐受同时发展 实验性疼痛和慢性疼痛表明镇痛耐受性 在长期阿片类药物治疗期间可能发生。如果出现急性耐受性，身体 以戒断症状、对有害刺激的痛觉过敏的形式产生依赖， 并且疼痛可能会比治疗前水平反弹增加 瑞芬太尼输注。 3. 长期使用阿片类药物会产生镇痛耐受性 慢性非恶性疼痛的治疗。在研究 3 中，慢性非阿片类药物使用 疼痛患者将接受镇痛效果的安慰剂对照研究 静脉注射瑞芬太尼治疗前后对急性实验性和慢性疼痛的影响 经过为期 9 周的随机平行设计、双盲试验。四十 受试者将接受阿片类药物氢吗啡酮，20 名对照组将接受 接受三环类抗抑郁药阿米替林。在最初的3结束时 周滴定期和固定剂量 6 周后再次进行，I.V. 将重复瑞芬太尼输注以重建剂量反应曲线 用于实验性和慢性疼痛。