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，该国510万处方阿片类药物滥用者中有相当数量(40%-50%)持续遭受疼痛，但阿片类止痛剂的治疗不仅因为对寻求药物和成瘾的担忧，而且还因为阿片类药物滥用对疼痛系统的神经生理学后果而复杂化。与疼痛直接相关的是阿片类药物滥用的神经反应是阿片诱导的痛觉过敏(OIH)，即与持续接触阿片类药物相关的对有害刺激高度敏感的状态，导致疼痛的矛盾增加和阿片类药物止痛效果的降低。阿片类药物诱导的痛敏在服用替代药物(如美沙酮、丁丙诺啡)治疗阿片依赖的患者中得到了很好的证明；值得注意的是，研究人员有新的试点数据表明，GABA激动剂加巴喷丁(GPN)显著降低了美沙酮患者的OIH(Compton等人，2010年)，这为阿片滥用者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使用，拟议的研究将全面评估慢性GPN疗法在丁丙诺啡疗法的处方阿片滥用者中治疗OIH的疗效，并研究这些效应是如何通过慢性疼痛的存在而调节的。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，计划在三年内完成，预计将提供关于GPN治疗阿片类药物滥用者OIH疗效的重要、有效和及时的细节。重要的是，这项工作将扩大感兴趣的临床人口，将重点放在处方阿片类药物滥用者身上，这是一群慢性疼痛和成瘾使结果复杂化的患者，并使他们特别容易受到治疗不足或疼痛管理不善的影响。测试GPN是已知的第一种治疗OIH的药物疗法，它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.