Optimizing Pain Treatment while Reducing Abuse Liability in Opioid Dependence

描述（由申请人提供）：处方阿片类药物的滥用已经成为一种全国性的流行病，导致吸毒成瘾的巨大社会成本。个体反复给出疼痛作为潜在和维持这种疾病的主要原因，但关于疼痛如何影响药物滥用风险的知识有限。尽管行为药理学实验已经验证了药物作用的主观和客观测量作为滥用潜力的临床有价值的预测指标的使用，但很少有系统的研究全面检查了阿片类镇痛药暴露后阿片类药物依赖者的镇痛特性和滥用倾向测量。该申请是为K23指导病人导向的研究职业发展奖，为博士大卫·安德鲁·汤普金斯发展一个独立的研究事业，开展临床试验，调查有效的策略，管理疼痛，同时减少滥用阿片类药物依赖的人的责任。在他的培训计划中，Tompkins博士建议通过同时攻读临床研究健康科学硕士学位，参与正在进行的成瘾药物治疗临床试验，并完成两项新的试验，检查阿片类药物依赖者急性疼痛管理的有效策略，来扩展他在临床试验设计，管理和分析方面的知识。新的试验将使汤普金斯博士获得定量感觉测试（QST）方面的专业知识，这是一种涉及多种实验性疼痛技术的综合评估方法，可以帮助研究人员和临床医生评估疼痛体验和有效的疼痛治疗。QST很少用于阿片类药物依赖人群，但最终可能为这些患者的未来疼痛研究提供有效可靠的模型。Tompkins博士将采用双盲安慰剂对照设计来测量静脉注射氢吗啡酮和丁丙诺啡的镇痛作用（实验疼痛阈值和耐受性的变化）、主观和客观药物效应，分为三组：无痛美沙酮维持参与者（N=30）、无痛丁丙诺啡维持参与者（N=30）和丁丙诺啡维持慢性肌肉骨骼疼痛的参与者（N=30）。收集这三个独立人群的QST和滥用责任数据，将进一步研究维持剂和慢性肌肉骨骼疼痛在显著增加疼痛阈值和耐受性所需药物量中的重要性。对QST镇痛反应的个体差异将进行检查，包括使用疼痛灾难化量表(PCS) -一个客观测量疼痛的重要预期和情绪方面的量表。这两项临床试验将补充培训计划，并帮助Tompkins博士作为独立疼痛和成瘾研究人员的职业发展，其结果可用于准备R01，以(1)将工作扩展到更大的急性疼痛治疗的2/3期对照临床试验，和/或(2)临床试验以探索额外的镇痛药物或输送系统。

DESCRIPTION (provided by applicant): The abuse of prescription opioids has become a national epidemic, contributing to the enormous societal costs of drug addiction. Individuals repeatedly give pain as a leading reason underlying and maintaining this disorder, but there exists limited knowledge into how pain influences the risk for drug abuse. Although behavioral pharmacology experiments have validated the use of subjective and objective measurements of drug effects as clinically valuable predictors of abuse potential, few systematic investigations have comprehensively examined both the analgesic properties and abuse liability measurements in persons with opioid dependence after exposure to opioid analgesics. This application is for a K23 Mentored Patient-Oriented Research Career Development Award for Dr. David Andrew Tompkins to develop an independent research career in conducting clinical trials investigating effective strategies for the management of pain while reducing abuse liability in persons with opioid dependence. In his training plan, Dr. Tompkins proposes to expand his knowledge of clinical trial design, management, and analysis by concurrently pursuing a Master in Health Science degree in Clinical Investigation, participating in ongoing clinical trials of pharmacological treatment of addiction, and completing two new trials examining effective strategies for the management of acute pain in persons with opioid dependence. The new trials will allow Dr. Tompkins to gain expertise in quantitative sensory testing (QST) - a comprehensive evaluation methodology involving multiple experimental pain techniques that can assist researchers and clinicians in assessing both pain experiences and effective pain treatments. QST has rarely been used in opioid dependent populations but may ultimately provide a valid and reliable model for future pain research with these patients. Dr. Tompkins will utilize a double-blind placebo controlled design to measure the analgesic (change in experimental pain threshold and tolerance), subjective, and objective drug effects provided by intravenous doses of hydromorphone and buprenorphine in 3 groups: pain-free methadone maintained participants (N=30), pain-free buprenorphine maintained participants (N=30), and buprenorphine maintained participants with chronic musculoskeletal pain (N=30). Collection of QST and abuse liability data in these three separate populations will additionally allow for an investigation of the importance of maintenance agent and chronic musculoskeletal pain in the amount of drug required for significant increases in pain threshold and tolerance. Individual differences in analgesic response to QST will be examined, including use of the pain catastrophizing scale (PCS) - a scale that objectively measures important anticipatory and emotional aspects of pain. These two clinical trials will complement the training plan and aid in Dr. Tompkins' career development as an independent pain and addiction researcher and the results can be used in preparation of an R01 to (1) extend the work to larger Phase 2/3 controlled clinical trials of acute pain treatment, and/or (2) clinical trials to explore additiona analgesic medications or delivery systems.