Opioid-induced Hyperalgesia in Prescription Opioid Abusers: Effects of Pregabalin

描述（由申请人提供）：处方阿片类药物滥用者疼痛的临床管理对医疗保健专业人员提出了挑战。流行病学数据表明，该国510万处方阿片类药物滥用者中有相当一部分（40-50%）持续遭受疼痛，但阿片类镇痛剂治疗不仅因对药物寻求和成瘾的担忧而复杂化，而且还因阿片类药物滥用对疼痛系统的神经生理学后果而复杂化。与疼痛直接相关，阿片类药物滥用的神经反应越来越受到重视，阿片类药物诱导的痛觉过敏（OIH），或与持续暴露于阿片类药物相关的对有害刺激敏感性提高的状态，并导致疼痛的矛盾增加和阿片类镇痛作用的降低。阿片类药物诱导的痛觉过敏已在使用替代药物的患者中得到充分证实（例如，美沙酮、丁丙诺啡）用于治疗阿片类药物依赖;值得注意的是，研究者有新的试验数据显示GABA激动剂加巴喷丁（GPN）显著降低美沙酮患者的OIH（Compton等人，2010），提供了阿片类药物滥用者OIH药物治疗的第一个经验证据。为了指导其在临床环境中的使用，拟议的研究将全面评估慢性GPN治疗在接受丁丙诺啡治疗的处方阿片类药物滥用者人群中治疗OIH的疗效，并研究这些影响如何通过慢性疼痛的存在介导。直接建立在调查组的数据和正式研究活动的基础上，计划中的项目的设计和人员配备将在三年内完成，预计将提供有关GPN治疗阿片类药物滥用者OIH疗效的重要，有效和及时的细节。重要的是，这项工作将扩大感兴趣的临床人群，重点关注处方阿片类药物滥用者，这是一组慢性疼痛和成瘾使结果复杂化的患者，并且使他们特别容易受到治疗不足或疼痛管理不良的影响。测试GPN是治疗该人群中OIH的第一种已知药物疗法，是为滥用处方阿片类药物的患者提供充分缓解疼痛的重要一步。

DESCRIPTION (provided by applicant): The clinical management of pain in prescription opioid abusers presents a challenge to the health care professional. Epidemiological data indicate that a substantial number (40-50%) of the 5.1 million prescription opioid abusers in this country suffer pain on an ongoing basis, yet treatment with opioid analgesics is complicated not only by concerns about drug-seeking and addiction, but also by the neurophysiologic consequences of opioid abuse on pain systems. With direct relevance to pain, an increasingly appreciated neural response to opioid abuse is opioid-induced hyperalgesia (OIH), or a state of heightened sensitivity to noxious stimuli associated with ongoing exposure to opioids, and resulting in a paradoxical increase in pain and decrease in opioid analgesic effects. Opioid-induced hyperalgesia has been well-demonstrated in patients on substitution medication (e.g., methadone, buprenorphine) for the treatment of opioid dependence; notably the investigators have novel pilot data showing that the GABA-agonist gabapentin (GPN) significantly decreases OIH in methadone patients (Compton et al., 2010), providing the first empirical evidence of a pharmacotherapy for OIH in opioid abusers. In an effort to guide its use in the clinical setting, the proposed research will comprehensively evaluate the efficacy of chronic GPN therapy to treat OIH in a well-described population of prescription opioid abusers on buprenorphine therapy, and examine how these effects are mediated by the presence of chronic pain. Directly building upon the data and formalized research activities of the investigative group, the planned project is designed and staffed to be completed in three years, and is anticipated to provide important, valid, and timely detail on the efficacy of GPN for the treatment of OIH in opioid abusers. Importantly, this work will expand the clinical population of interest to focus on prescription opioid abusers, a group of patients for whom chronic pain and addiction complicate outcome, and leaves them uniquely vulnerable to under-treatment or poor pain management. Testing the GPN, the first-known pharmacotherapy to treat OIH in this population, is an important step toward providing adequate pain relief for patients who abuse prescription opioids.