Pharmacological treatment of pain among persons with opioid addiction: A systematic review and meta-analysis with implications for drug development.

The clinical features and neurobiology of pain and opioid use disorder (OUD) are inextricably linked. Despite emerging evidence supporting the negative impact of ongoing pain in the treatment of OUD, the pharmacological management of pain in the presence of OUD has received limited attention. We sought to systematically review the studies investigating pharmacotherapies for pain among persons with OUD. Eligible studies had participants with OUD and outcomes including evoked or spontaneous pain. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Out of 1,097 studies that met the search criteria, 12 studies provided data relevant to the research question-five laboratory studies and seven clinical trials. Random effects pooled estimates suggested no significant difference between groups at baseline but a response favoring the active treatment group over placebo, with nonsignificant heterogeneity between studies. Findings from these studies provide preliminary evidence for analgesic and antihyperalgesic effects of gabapentin, GABA agonists, and NMDA antagonists among persons with OUD. To establish the tradeoffs between the analgesic effects and abuse liability of these compounds, further well-controlled clinical trials are required among persons with OUD. This review also underscores the need for methodological enhancement in drug development for pain in OUD. Future research should address the clinical and neurobiological overlap between pain- and addiction-related phenomena. Transdisciplinary approaches may identify biomarkers of these shared phenomena and their neural substrates. The development of novel therapeutics for pain in OUD may be accelerated by such integration of pain and addiction research.