Effective Network to advance Scientific Evidence related to Mechanisms of music-Based interventions (ENSEMBLE) - PROJECT SUMMARY/ABSTRACT Pain is a public health problem, a major driver of health care seeking and medication use, a major cause of disability, and a key factor affecting quality of life and productivity. Music-based interventions (MBIs) including music therapy (MT) are known to be effective for managing pain in several populations. However, substantial gaps remain in understanding the mechanisms of action (e.g., cognitive, genomic, metabolomic, and neurologic) by which MBIs influence pain. Barriers to advancing this mechanistic r esearch have included: 1) lack of meaningful and inclusive collaboration between music therapists and mechanistic scientists; 2) inconsistent application and definition of MBIs, patient-reported outcomes, and biological measures; and 3) lack of funding and infrastructure to support interdisciplinary pilot projects. This proposal seeks to establish a NEW collaborative network: Effective Network to advance Scientific Evidence related to Mechanisms of music-Based interventions for pain and support coLlaborative Efforts (ENSEMBLE) to advance collaborative research efforts investigating the mechanisms by which MBIs influence various pain phenotypes. ENSEMBLE will be built on a foundation of well-integrated medical MT practice, strong mechanistic science in integrative health and medicine (IHM), research investigating MT and biological mechanisms of pain in SCD and the BraveNet Practice-Based Research Network. At the outset, SCD will serve as the pain-related condition of interest given the expertise of ENSEMBLE team members at present and strong preliminary data, but other pain conditions will be addressed in future years. ENSEMBLE will be led by investigators from University Hospitals of Cleveland/Case Western Reserve University, University of California Irvine, The Louis Armstrong Center for Music & Medicine, Icahn School of Medicine at Mount Sinai, and Emory University. ENSEMBLE will establish a vibrant collaborative network of music therapists, mechanistic scientists, music intervention researchers, IHM resear chers, and patient-advocacy organizations. The Specific Aims are to: (1) promote meaningful, inclusive, and interdisciplinary collaboration between music therapists, mechanistic scientists, and IHM researchers; (2) develop a comprehensive framework for conducting mechanistic studies in MBIs for pain management; and (3) advance multiple pilot projects investigating novel biological mechanisms of action underlying the effects of MBIs for various pain phenotypes. The IMPACT of ENSEMBLE will be instrumental in 1) promoting meaningful interdisciplinary dialogue; 2) building multi-institutional capacity for initiating MBI research in pain management; 3) generating preliminary data for future R21 or R34 grant proposals; 4) improving data infrastructure; 5) developing future MT clinician researchers; 6) focusing future scientific efforts; and 7) disseminating best practices.