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.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Human Development Research Subcommittee (NIDA)
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Chambers, Jessica Campbell
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Johns Hopkins University
Schools of Medicine
United States
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Kosten, Thomas R; Domingo, Coreen B; Shorter, Daryl et al. (2014) Vaccine for cocaine dependence: a randomized double-blind placebo-controlled efficacy trial. Drug Alcohol Depend 140:42-7
Tompkins, D Andrew; Smith, Michael T; Mintzer, Miriam Z et al. (2014) A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine. J Pharmacol Exp Ther 348:217-26
Liao, Caiyun; Zhang, Dongyu; Mungo, Chemtai et al. (2014) Is diabetes mellitus associated with increased incidence and disease-specific mortality in endometrial cancer? A systematic review and meta-analysis of cohort studies. Gynecol Oncol 135:163-71
Tompkins, David Andrew; Smith, Michael T; Bigelow, George E et al. (2014) The effect of repeated intramuscular alfentanil injections on experimental pain and abuse liability indices in healthy males. Clin J Pain 30:36-45