PROJECT SUMMARY Chronic pain is a major health concern and one of the most common reasons adults seek medical care [1]. It is associated with substantial morbidity linked to reduced quality of life, restricted mobility, depression, and opioid dependence [2]. In 2016, approximately 50 million U.S. adults were afflicted with chronic pain, with approximately 40% of them having high-impact chronic pain [2]. The societal cost of chronic pain is estimated at $560 billion annually in direct medical expenses, lost productivity, and disability programs [3]. The biological mechanisms that prevent the resolution of acute pain after the initial insult and drive the transition from acute to chronic pain are poorly understood [4,5]. The lack of rigorously validated biomarkers to predict which patients are more susceptible to the transition from acute to chronic pain states is thus a major gap hindering the development and implementation of population-wide and individualized preventive pain interventions [6]. The primary goal of this project is to establish the A2CPS Omics Data Generation Center (ODGC) to generate genomic variant, metabolomic, lipidomic, proteomic, and exRNA data from two pain cohorts consisting of 1800 subjects each, with biofluid samples collected at baseline, 6 weeks, and 3 months after an acute pain episode. These samples will be used to generate multi-omic data to validate 40 primary outcome biomarkers indicating susceptibility or resilience to development of chronic pain, as well as to identify new candidate biomarkers.