Abstract This research project aims to compare multi-domain pain phenotypes across various pain conditions, with a specific focus on the lower back, knee, and temporomandibular joint (TMJ). The objective is to bridge a crucial gap in our comprehension of pain perception and manifestation within clinical patient populations, which holds significant implications for developing targeted and personalized pain management strategies. The proposed supplement seeks to conduct a comprehensive comparison of clinical pain phenotypes across these anatomical sites by integrating data and research methodologies from the National Institutes of Health (NIH) Healing Addiction Long-Term (HEAL) Initiative's Back Pain Consortium (BACPAC) and the Restoring Joint Health and Function to Reduce Pain (RE-JOIN) Consortium. By combining data on patients' pain experiences, psychological distress, functional impairment, and quality of life with evaluations of innervation shifts at pathological sites, this study aims to delineate similarities and differences in how chronic musculoskeletal pain manifests across different anatomical locations. Musculoskeletal pain is a significant driver of opioid abuse and a central focus of multiple HEAL programs, including BACPAC and RE-JOIN. Collaborative efforts between principal investigators from BACPAC (Sowa and Vo) and RE-JOIN (Allen, Almarza, Cruz-Almeida) are underway to bridge gaps between these initiatives. As part of these efforts, Specific Aim 1 aims to expand the RE-JOIN Human Study to include blood collection and perform BACPAC analysis, comparing biomarkers across chronic pain conditions. Specific Aim 2 focuses on characterizing the innervation patterns of BACPAC samples obtained from different anatomical sites, while Specific Aim 3 aims to compare deep pain phenotype data among patients with back, knee, and TMJ conditions. Through these aims, this research endeavor seeks to deepen our understanding of pain mechanisms and pave the way for more effective personalized pain management interventions.