Opioid Responsivity/ Analgesic Tolerance in Chronic Pain

描述（申请人？s abstract）：1.我们将检验这个假设， 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 患者对实验诱导疼痛和持续临床疼痛的反应 静脉输注瑞芬太尼对于实验性疼痛，我们将使用一个模型， 结合联合收割机非伤害性加热和局部辣椒素， 皮肤继发性痛觉过敏在健康志愿者中，这种模型是阿片样物质 反应灵敏。研究1是一项为期两个阶段的安慰剂对照研究， 实验和临床疼痛的短暂输液的高疗效， 超短效阿片类药物瑞芬太尼治疗慢性疼痛60例 患者 2.在研究2中，我们将确定是否延长静脉输注瑞芬太尼 在阿片类药物初治志愿者中， 伤害性热刺激和实验诱导的皮肤继发性 痛觉过敏然后，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的同时发展， 实验性疼痛和慢性疼痛表明， 在长期的阿片类药物治疗中可能会发生。如果出现急性耐受性， 以戒断症状形式的依赖，对有害刺激的痛觉过敏， 并且在治疗前水平上的疼痛反弹增加可能遵循 瑞芬太尼输注。 3.镇痛耐受性已被证明在长期阿片类药物治疗期间会产生 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 疼痛患者将接受一项安慰剂对照的镇痛效果研究 静脉注射瑞芬太尼对急性实验性疼痛和慢性疼痛的作用， 在9周、随机平行设计、双盲试验之后。四十 受试者将接受阿片样物质氢吗啡酮，20名对照组将 接受三环类抗抑郁药阿米替林。在最初的3年结束时， 6周滴定期和6周固定给药后再次给药， 将重复输注瑞芬太尼以重建剂量-反应曲线 治疗实验性和慢性疼痛

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.