PROJECT SUMMARY Chronic pain represents a public health crisis that affects more than 100 million Americans and costs over $500 billion dollars annually. Chronic musculoskeletal pain conditions comprise 70-80% of all chronic pain. An estimated 8% of US adults suffer from high-impact chronic pain, or pain associated with substantially restricted work, social, and self-care activities for six or more months. Chronic pain—and high-impact chronic pain in particular—is often treated with prescription opioids and is linked to opioid-use disorder. Multidisciplinary chronic pain treatments show incomplete recovery at the population level. However, subgroups of individuals completely respond, do not change, or even worsen following pain management. Thus, robust and validated diagnostic and prognostic biomarkers are needed to identify those with high-impact chronic pain and determine the trajectory of outcome (i.e., recovery versus persistence), respectively. Therefore, our overall goal is to discover and validate diagnostic and prognostic biomarkers for musculoskeletal high-impact chronic pain. This goal will require comprehensive, multidimensional assessments with an integrated dataset and a sophisticated computational analysis pipeline to yield reliable and validated diagnostic and prognostic biomarkers. To this end, we have assembled an interdisciplinary research and clinical team to implement the HEAL initiative. The goal of this initiative is to elucidate diagnostic and prognostic biomarker signatures of chronic pain by integrating CNS, multiomic, sensory, functional, psychosocial, and demographic domains. We will achieve this goal through two specific aims: (1) develop diagnostic and prognostic markers of musculoskeletal high-impact chronic pain following multidisciplinary pain treatment (R61 Discovery Phase) and (2) analytically validate the multimodal signatures developed in the first aim (R33 Validation Phase). This proposal will yield valid and clinically useful diagnostic and prognostic biomarker signatures to facilitate risk and treatment stratification in patients with musculoskeletal chronic pain. Such biomarkers are essential to develop safer, more effective patient-specific treatment strategies, particularly for those who are refractory to current pain management options. We will also identify potentially modifiable biological and behavioral factors that can change the course of the pain trajectory and thereby reduce the impact of chronic pain on the individual and society as a whole.

PROJECT NARRATIVE More than 100 million Americans live with chronic pain, 20 million of whom suffer from high-impact chronic pain that substantially restricts work, social, and self-care activities for six or more months. Our proposed HEAL initiative aims to discover and validate clinically useful diagnostic and prognostic biomarker signatures to identify those with musculoskeletal high-impact chronic pain and determine the trajectory of outcome. Such biomarkers are essential to facilitate risk and treatment stratification in patients with chronic pain and to develop safer, more effective patient-specific treatment strategies.