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卫生保健专业人员提出了挑战。流行病学数据表明，在美国510万处方阿片类药物滥用者中，有相当数量（40-50%）的人持续遭受疼痛，但阿片类镇痛药的治疗不仅由于对药物寻求和成瘾的担忧，而且由于阿片类药物滥用对疼痛系统的神经生理后果而变得复杂。与疼痛直接相关的是，阿片类药物滥用的神经反应是阿片类药物诱导的痛觉过敏（OIH），或对持续暴露于阿片类药物的有害刺激高度敏感的状态，导致疼痛增加和阿片类药物镇痛作用减少的矛盾现象。阿片类药物引起的痛觉过敏已经在使用替代药物（如美沙酮，丁丙诺啡）治疗阿片类药物依赖的患者中得到充分证明；值得注意的是，研究人员有新的试点数据显示，gaba激动剂加巴喷丁（GPN）可显著降低美沙酮患者的OIH (Compton et al., 2010)，为阿片类药物滥用者OIH的药物治疗提供了第一个经验证据。为了指导其在临床环境中的应用，本研究将全面评估慢性GPN治疗处方阿片类药物滥用丁丙诺啡治疗OIH的疗效，并研究慢性疼痛的存在如何介导这些效果。计划中的项目直接建立在调查小组的数据和正式研究活动的基础上，其设计和人员配备将在三年内完成，预计将提供关于GPN治疗阿片类药物滥用者OIH疗效的重要、有效和及时的详细信息。重要的是，这项工作将扩大关注处方阿片类药物滥用者的临床人群，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善的影响。GPN是目前已知的首个治疗OIH的药物疗法，是为滥用处方阿片类药物的患者提供足够的疼痛缓解的重要一步。

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.