This R21 resubmission proposes to systematically study the association between chronic musculoskeletal pain, delay discounting, opioid withdrawal and pain catastrophizing in patients on methadone maintenance for opioid use disorder (OUD). The epidemic of opioid overdose deaths continues to rise, killing more persons in 2017 then at the height of the HIV/AIDS epidemic. Medication assisted treatment, utilizing methadone or buprenorphine, is the standard of care for the treatment of OUD. However, co-occurring chronic pain can reduce treatment efficacy and is associated with relapse and poor retention in treatment. Mechanisms by which chronic pain may influence the impulsive decision-making (e.g., drug relapse) in persons with OUD have not been well characterized. Two factors that can influence decisions to use drugs are impulsivity and acute opioid withdrawal. Delay discounting is a model of impulsive decision-making and refers to the observation that delaying a consequence reduces its subjective value. Though delay discounting was originally thought to be trait-like, situational stressors have recently been shown to increase discounting, including acute opioid withdrawal. It is not known if a chronic stressor (i.e., chronic pain) has a similar effect on discounting or whether there are greater changes to discounting in the presence of both an acute and chronic stressor than either stressor alone. Trait pain catastrophizing is thought to increase attention and focus on pain and influence the choice of coping strategies used to respond to pain. It could play an important role in the impulsive decision to use drugs for immediate pain relief at the expense of abstinence, especially as a function of chronic pain. This proposal will test how chronic pain is associated with increases in impulsive decision-making in OUD, whether impulsive decision-making is greater when undergoing opioid withdrawal for OUD patients with and without chronic pain, and how catastrophizing may modify the association between chronic pain and impulsive decision- making. The proposed study will recruit two groups of patients maintained on methadone for OUD ? individuals with (PAIN) and without (NO PAIN) chronic musculoskeletal pain, matched on characteristics that can influence delay discounting. Each group will have two double-blind experimental sessions in counterbalanced order: 1) control condition [intramuscular (IM) injection of normal saline] during peak methadone effects and 2) IM naloxone-precipitated opioid withdrawal. The same delay discounting tasks will be measured during each session.
The specific aims are to: (1) Determine the effect of aversive stressors on delay discounting in persons in methadone maintenance; and (2) Investigate the degree to which trait pain catastrophizing modifies the association between opioid withdrawal and delay discounting. If withdrawal and catastrophizing were found to affect impulsive decision-making, future research could extend the study of these variables to determine if they play an explicitly causal role in decisions to use opioids or to relapse, and to develop interventions to remediate impulsivity leading to relapse, thereby improving treatment outcomes.
The United States is currently facing a tremendous public health crisis in the form of opioid overdose deaths, especially amongst persons with opioid use disorder. If successful, this proposal could improve treatment of the large proportion of patients with opioid use disorder and co-occurring chronic pain by providing critical information on ways to improve retention and reduce relapse during methadone maintenance. Successful results may also show that delay discounting, the primary outcome in this proposal, could serve as a surrogate endpoint in clinical trials assessing primary or secondary prevention of opioid use disorders ? improving the rapidity of moving evidence-based treatments into clinical practice.
