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 患者实验诱发的疼痛和持续临床疼痛的反应 到I.V.雷替甘坦基输注。对于实验性疼痛，我们将使用一个模型 结合非妇女加热和局部辣椒素，产生稳定的区域 皮肤继发性痛觉过敏。在卫生志愿者中，该模型是阿片类药物 响应迅速。研究1是对安慰剂对照的两节对影响的影响 高疗效短暂输注的实验和临床疼痛， 超短作用的阿片类药物雷曲苯基在60非阿片类药物中使用慢性疼痛 患者。 2。在研究2中，我们将确定是否长时间的静脉雷替甘坦基输注 在阿片类药物中，志愿者将对这两者产生急性镇痛耐受性 有害的热刺激和实验诱导的皮肤次级 痛苦。然后，我们将测试患有持续慢性疼痛的患者。 证明急性镇痛耐受性同时发展 实验性疼痛和慢性疼痛将表明镇痛耐受性是 在长期阿片类药物疗法中可能。如果急性耐受性发展，物理 以戒断症状的形式依赖性，痛苦刺激的痛苦， 而且，在预处理水平上疼痛的反弹增加可能遵循 雷替甘坦基输注。 3。已证明在长期阿片类药物期间发展出镇痛耐受性 慢性非恶性疼痛的治疗。在研究3中，非阿片类药物使用慢性 疼痛患者将接受镇痛作用的安慰剂对照研究 i.v.在急性实验和慢性疼痛之前和 在9周后，随机并行设计，双盲试验。四十 受试者将接收阿片类氢电上的液压率和20人的对照组 接收三环抗抑郁药。在最初的3结束时 周期滴定期以及固定给药6周后，i.v. 将重复雷芬太尼输注以重建剂量反应曲线 用于实验和慢性疼痛。