Conceptual Design and Protocol for the Acute to Chronic Pain Signatures Program (A2CPS)

The United States faces a crisis due to the high prevalence of chronic pain and associated opioid use disorder and overdose deaths. While the majority of acute pain resolves within weeks, 20-50% of people with acute pain persists well beyond the initial insult. The mechanisms driving the transition from acute to chronic pain states are poorly understood. Through a National Institutes of Health (NIH)-funded initiative, the A2CPS Program was formed to identify putative biomarkers (individual or biosignature combinations) that predict susceptibility or resilience for the transition from acute to chronic pain after surgery (total knee replacement and thoracotomy). The A2CPS consortium includes two multisite clinical centers (MCCs), one Clinical Coordinating Center (CCC), one Data Integrations and Research Center (DIRC), and 3 OMICS centers along with representation from the NIH Pain Consortium, Common Fund, and National Institute of Drug Abuse. During an initial planning year, the A2CPS developed study aims, biomarker selection, and a study protocol. Candidate biomarkers were selected across multiple domains (clinical, biospecimen, psychosocial, and brain structure/function). Data will be collected from two MCCs (n=3600 individuals) before, during and after surgery to determine factors that predict the transition from acute to chronic pain 6 months later. Subjects will be comprehensively phenotyped across measures of pain, behavioral and psychological, quantitative sensory testing, brain imaging, proteomics, genomics, metabolomics, and lipidomics. Determining biomarkers prior to and in the acute phase after surgery could provide the basis for interventions to prevent the onset of chronic pain and contribute to our understanding of the dynamic processes underlying the transition from acute to chronic pain. Furthermore, if any of the predictive biomarkers play a mechanistic role in development of chronic pain, then the molecules, pathways, constructs, and/or brain circuits identified could serve as new potential therapeutic targets for reversing chronic pain or increasing patients’ resilience. National Institutes of Health Grants: NS112873, NS118922, DA049110, NS112874, DA049115, DA049116, DA049113.