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对瑞芬太尼静脉输注的实验诱导疼痛和持续临床疼痛的反应来检验潜在疼痛机制是阿片类药物敏感性决定因素的假设。对于实验性疼痛，我们将使用一个模型，它结合了非损伤性加热和局部辣椒素，以产生稳定的皮肤继发性痛觉过敏。在健康志愿者中，该模型对阿片类药物有反应。研究1是在60名使用慢性疼痛的非阿片类药物患者中进行的高效超短效阿片类药物瑞芬太尼脑输注对实验性和临床疼痛的影响的两个阶段、安慰剂对照研究。(2)在研究2中，我们将确定是否在阿片类药物初治志愿者中长时间静脉输注瑞芬太尼将产生对有害热刺激和实验诱导的皮肤继发性痛觉过敏的急性镇痛耐受。然后，我们将测试患有持续慢性疼痛的患者，这将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，则在雷米芬太尼输注后可能会出现戒断症状、对有害刺激的痛觉过敏和疼痛反弹增加等形式的身体依赖。(3)在慢性非恶性疼痛的长期阿片类药物治疗期间，尚未显示出镇痛耐受性。在研究3中，非阿片类药物使用慢性疼痛患者将在9周随机平行设计双盲试验之前和之后进行静脉注射瑞芬太尼对急性实验性疼痛和慢性疼痛的镇痛作用的安慰剂对照研究。40名受试者将接受阿片类氢吗啡酮，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和固定给药6周后，将重复静脉输注瑞芬太尼，以重建实验性和慢性疼痛的剂量-反应曲线。