REPRINTED WITH PERMISSION OF IASP – PAIN 164 (2023): 1912–1926: Predicting chronic postsurgical pain: current evidence anda novel program to develop predictive biomarker signatures

Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because thepathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Painbiomarkers could potentially identify and measure biological pathways and phenotypical expressions that arealtered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinicalbiomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fundlaunched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop theminto biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discussescandidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic,neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will providethe most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken todate. Data and analytic resources generated by A2CPS will be shared with the scientific community in hopes thatother investigators will extract valuable insights beyond A2CPS’s initial findings. This article will review the identifiedbiomarkers and rationale for including them, the current state of the science on biomarkers of the transition fromacute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.