Supplemental Digital Content is Available in the Text.Individuals with post–Coronavirus-19 condition report elevated pain, fatigue, psychological impact, and functional limitation similar, but less severe, than those with fibromyalgia and chronic fatigue syndrome.

Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered 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 clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

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Chronic pain has become a global health problem contributing to years lived with disability and reduced quality of life. Advances in the clinical management of chronic pain have been limited due to incomplete understanding of the multiple risk factors and molecular mechanisms that contribute to the development of chronic pain. The Acute to Chronic Pain Signatures (A2CPS) Program aims to characterize the predictive nature of biomarkers (brain imaging, high-throughput molecular screening techniques, or “omics,” quantitative sensory testing, patient-reported outcome assessments and functional assessments) to identify individuals who will develop chronic pain following surgical intervention. The A2CPS is a multisite observational study investigating biomarkers and collective biosignatures (a combination of several individual biomarkers) that predict susceptibility or resilience to the development of chronic pain following knee arthroplasty and thoracic surgery. This manuscript provides an overview of data collection methods and procedures designed to standardize data collection across multiple clinical sites and institutions. Pain-related biomarkers are evaluated before surgery and up to 3 months after surgery for use as predictors of patient reported outcomes 6 months after surgery. The dataset from this prospective observational study will be available for researchers internal and external to the A2CPS Consortium to advance understanding of the transition from acute to chronic postsurgical pain.

Rigorous experimental design with transparent reporting in biomedical science reduces risk of bias and allows for scientists to judge the quality of the research. Basic factors of rigor such as blinding, randomization, power analysis, and inclusion of both sexes impact the reproducibility by reducing experimental bias. We designed a systematic study to analyze basic factors of rigor, inclusion of sex, and whether data were analyzed or disaggregated by sex over the past 10 years in the journal PAIN. Studies that included humans reported randomization in 81%, blinding in 48%, and the use of a power analysis calculation in 27% over the past 10 years. Studies that included mice reported randomization in 35%, blinding in 70%, and the use of a power analysis in 9%. Studies that included rats reported randomization in 38%, blinding in 63%, and the use of power analysis in 12%. This study also found that human studies consistently included both sexes over the past decade, but less than 20% of data were disaggregated or analyzed for sex differences. Although mouse and rat studies predominately used males only, there has been a slight increase in inclusion of both sexes over the past few years. Justification for single-sex studies was below 50% in both human and rodent data. In both human and animal studies, transparency in reporting of experimental design and inclusion of both sexes should be considered standard practice and will result in improved quality and reproducibility of published research.