Optimizing Pain Treatment while Reducing Abuse Liability in Opioid Dependence

优化疼痛治疗，同时减少阿片类药物依赖的滥用责任

• 批准号: 8300440
• 负责人: David Andrew Tompkins
• 金额: $ 18.57万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8300440
• 关键词: Absence of pain sensation; Accident and Emergency department; Acute; Acute Pain; Address; Analgesics; Area; Attention; Biological Factors; Buprenorphine; Chronic; Clinical; Clinical Pharmacology; Clinical Trials; Clinical Trials Design; Clinical assessments; Collection; Complement; Complex; Conduct Clinical Trials; Controlled Clinical Trials; Data; Disease; Dose; Double-Blind Method; Drug Addiction; Drug abuse; Emotional; Environmental Risk Factor; Epidemic; Evaluation; Evaluation Methodology; Exhibits; Exposure to; Funding; Future; Goals; Grant; Health Sciences; Heating; Histocompatibility Testing; Hydromorphone; Hyperalgesia; Individual; Individual Differences; Intravenous; Investigation; Knowledge; Lead; Maintenance; Measurement; Measures; Medical; Mentored Patient-Oriented Research Career Development Award; Mentors; Methadone; Modeling; Musculoskeletal Pain; Opiate Addiction; Opioid; Opioid Analgesics; Outcome; Pain; Pain Measurement; Pain Research; Pain Threshold; Pain management; Pain-Free; Participant; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Phase; Placebo Control; Placebos; Population; Preparation; Procedures; Process; Property; Provider; Psychological Factors; Recruitment Activity; Research; Research Personnel; Risk; Sensory; Severities; System; Techniques; Testing; Training; Training Programs; Treatment outcome; Visit; Work; addiction; behavioral pharmacology; career; career development; chronic pain; cost; design; effective therapy; experience; nonmedical use; patient oriented; prescription opioid; prescription opioid abuse; pressure; research study; response; substance abuse treatment

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. PUBLIC HEALTH RELEVANCE: The treatment of pain with opioid medications has increased dramatically over the last 10 years, but so have the addiction problems due to those same prescription pain relievers. This grant proposes to provide Dr. David Andrew "Andy" Tompkins mentoring and other career development activities to become an independent and expert researcher on the relationship between pain and addiction. Additionally, Dr. Tompkins proposes to perform two experiments to examine the association between experimental acute pain and addiction in persons with opioid dependence. Understanding this association will lead to more effective treatments for both chronic pain and opioid dependence.

描述（由申请人提供）：滥用处方阿片类药物已成为一种全国性流行病，导致吸毒成瘾的巨大社会成本。个人反复给予疼痛作为一个主要原因的基础和维持这种疾病，但存在有限的知识如何疼痛影响药物滥用的风险。虽然行为药理学实验已经验证了使用主观和客观的测量药物的影响，滥用潜力的临床有价值的预测，一些系统的研究已经全面检查了阿片类药物依赖的人暴露于阿片类镇痛剂后的镇痛性能和滥用倾向的测量。本申请是为大卫安德鲁汤普金斯博士K23指导的以患者为导向的研究职业发展奖，以发展独立的研究生涯，进行临床试验，调查疼痛管理的有效策略，同时减少阿片类药物依赖者的滥用责任。汤普金斯博士在他的培训计划中提出，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，以研究阿片类药物依赖者急性疼痛管理的有效策略，来扩大他在临床试验设计，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）的专业知识-这是一种涉及多种实验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和可靠的模型。汤普金斯博士将采用双盲安慰剂对照设计来测量镇痛剂（实验痛阈和耐受性的变化）、主观和客观药物效应，由3组中氢吗啡酮和丁丙诺啡的静脉给药提供：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）。在这三个单独人群中收集QST和滥用倾向数据，将另外允许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。将检查QST镇痛反应的个体差异，包括使用疼痛灾难化量表（PCS）-一种客观测量疼痛的重要预期和情感方面的量表。这两项临床试验将补充培训计划，并帮助汤普金斯博士作为独立的疼痛和成瘾研究人员的职业发展，其结果可用于准备R 01，以（1）将工作扩展到更大的2/3期急性疼痛治疗对照临床试验，和/或（2）临床试验，以探索其他镇痛药物或递送系统。 公共卫生关系： 在过去的10年里，用阿片类药物治疗疼痛的人数急剧增加，但同样的处方止痛药也会导致成瘾问题。这项拨款建议为大卫安德鲁“安迪”汤普金斯博士提供指导和其他职业发展活动，使其成为疼痛和成瘾之间关系的独立和专家研究人员。此外，汤普金斯博士建议进行两项实验，以检查实验性急性疼痛与阿片类药物依赖者成瘾之间的关联。了解这种关联将导致更有效的治疗慢性疼痛和阿片类药物依赖。