Experimental Pain Responses and Clinical Pain Symptoms in Patients Receiving Opioid Agonist and Antagonist Treatment for Opioid Use Disorder: An Observational Study

Background. Opioid use disorder (OUD) treatment mainly involves long-term use of medications that either stimulate (agonists) or block (antagonists) mu-opioid receptors and that could potentially affect patients’ experiences of pain. We therefore conducted an observational study of pain symptoms and sensitivity in patients receiving opioid agonist and antagonist treatment for OUD, and healthy volunteers.Methods. Seventy-four OUD patients receiving the antagonist extended-release naltrexone (XR-NTX; n = 34) or opioid agonists (methadone or buprenorphine; n = 40), as well as 50 healthy volunteers participated in a single study session. Participants answered questions about their current pain symptoms, and completed a Cold Pressor Test (CPT) while we measured heart rate and salivary cortisol. Hypotheses and analyses were preregistered before data access. Group differences in chronic pain rates and cold pain responses were modeled with logistic, beta and linear regression and tested with likelihood ratio χ2- and F-tests.Results. Half of patients in either treatment reported living with chronic pain. Individual CPT responses were variable. Patients on opioid agonists and XR-NTX reported pain 2 and 9 seconds earlier than and removed their hand 34 and 46 seconds before healthy volunteers. These group differences align with prior findings of heightened pain sensitivity in agonist-maintained patients but were non-significant (ps = 1). Differences in cold pain intensity and cold pain-induced changes in heart rate and cortisol aligned with hypotheses but were also non-significant (ps ≥ 0.17). Conclusion. Consistent with prior observations, the current findings indicate that a considerable number of OUD patients experience persistent pain symptoms while undergoing either opioid agonists or XR-NTX treatment. Major detrimental or beneficial effects of these medications on pain and pain sensitivity seem unlikely however.