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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
4K23DA029609-05
Application #
9068855
Study Section
Training and Career Development Subcommittee (NIDA)
Program Officer
Lao, Guifang
Project Start
2012-07-01
Project End
2017-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Tompkins, D Andrew; Huhn, Andrew S; Johnson, Patrick S et al. (2018) To take or not to take: the association between perceived addiction risk, expected analgesic response and likelihood of trying novel pain relievers in self-identified chronic pain patients. Addiction 113:67-79
Jarvis, Brantley P; Holtyn, August F; Subramaniam, Shrinidhi et al. (2018) Extended-release injectable naltrexone for opioid use disorder: a systematic review. Addiction 113:1188-1209
Huhn, Andrew S; Strain, Eric C; Bigelow, George E et al. (2018) Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals. Anesthesiology :
Dunn, Kelly E; Finan, Patrick H; Andrew Tompkins, D et al. (2018) Frequency and correlates of sleep disturbance in methadone and buprenorphine-maintained patients. Addict Behav 76:8-14
Tompkins, D Andrew; Hobelmann, J Greg; Compton, Peggy (2017) Providing chronic pain management in the ""Fifth Vital Sign"" Era: Historical and treatment perspectives on a modern-day medical dilemma. Drug Alcohol Depend 173 Suppl 1:S11-S21
Dunn, Kelly E; Tompkins, D Andrew; Bigelow, George E et al. (2017) Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial. JAMA Psychiatry 74:885-893
Huhn, Andrew S; Tompkins, D Andrew; Dunn, Kelly E (2017) The relationship between treatment accessibility and preference amongst out-of-treatment individuals who engage in non-medical prescription opioid use. Drug Alcohol Depend 180:279-285
Tompkins, D Andrew; Johnson, Patrick S; Smith, Michael T et al. (2016) Temporal preference in individuals reporting chronic pain: discounting of delayed pain-related and monetary outcomes. Pain 157:1724-32
Drescher, Jack; Schwartz, Alan; Casoy, Flávio et al. (2016) The Growing Regulation of Conversion Therapy. J Med Regul 102:7-12
Tompkins, D Andrew; Sides, Jessica A; Harrison, Joseph A et al. (2015) Recruitment techniques for alcohol pharmacotherapy clinical trials: A cost-benefit analysis. Addict Disord Their Treat 14:211-219

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