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: 6302765
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-01-15 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6302765
• 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

(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. remifentanil infusion. For experimental pain we will use a model which combines non-injurious heating and topical capsaicin to produce stable areas of cutaneous secondary hyperalgesia. In healthy volunteers, this model is opioid responsive. Study 1 is a two session, placebo-controlled study of the effect on experimental and clinical pain of brain infusions of the high efficacy, ultra-short acting opioid remifentanil in 60 non-opioid using chronic pain patients. (2) In study 2 we will determine whether a prolonged i.v. remifentanil infusion in opioid-naive 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 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 remifentanil infusion. (3) Analgesic tolerance has not 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. remifentanil 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 amitriptyline. At the end of the initial 3 week dose titration period and again after 6 weeks of fixed dosing, the i.v. remifentanil infusion will be repeated to reconstruct the dose-response curves for experimental and chronic pain.

(1) 我们将通过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的临床疼痛对静脉注射的反应，来检验以下假设：潜在的疼痛机制是阿片类药物敏感性的决定因素。瑞芬太尼输液。对于实验性疼痛，我们将使用一种模型，该模型结合了非伤害性加热和局部辣椒素，以产生稳定的皮肤继发性痛觉过敏区域。在健康志愿者中，该模型对阿片类药物有反应。研究 1 是一项两期安慰剂对照研究，研究了 60 名非阿片类药物使用的慢性疼痛患者脑部输注高效、超短效阿片类药物瑞芬太尼对实验和临床疼痛的影响。 (2) 在研究 2 中，我们将确定是否延长静脉注射。未使用阿片类药物的志愿者输注瑞芬太尼会对有害热刺激和实验诱导的皮肤继发性痛觉过敏产生急性镇痛耐受。然后，我们将测试患有持续慢性疼痛的患者，这表明在长期阿片类药物治疗期间镇痛耐受是可能的。如果出现急性耐受性，输注瑞芬太尼后可能会出现戒断症状、对有害刺激的痛觉过敏以及疼痛较治疗前水平反弹增加等形式的身体依赖性。 (3) 慢性非恶性疼痛的长期阿片类药物治疗并未显示出镇痛耐受性。在研究 3 中，使用非阿片类药物的慢性疼痛患者将接受一项关于静脉注射镇痛效果的安慰剂对照研究。瑞芬太尼在为期 9 周的随机平行设计双盲试验前后对急性实验性疼痛和慢性疼痛的影响。 40 名受试者将接受阿片类药物氢吗啡酮，20 名对照组将接受三环阿米替林。在最初的 3 周剂量滴定期结束时以及在 6 周的固定剂量后再次进行，静脉注射。将重复瑞芬太尼输注，以重建实验性疼痛和慢性疼痛的剂量反应曲线。