Mechanical and non-mechanical contributions to chronic neck, shoulder, arm, and back pain in full-busted women - Abstract Approximately 130 million individuals in the US (39% of the US population) are living with chronic musculoskeletal pain. Women experience more localizations of pain across their lifespan. Women report significantly more pain in the neck, shoulders, arms, back, and breasts due to altered musculoskeletal activity within in the neck and thoracic region due to the presence of breast tissue. Neck, shoulder, arm, and back (NSAB) pain has been strongly linked to bra cup size. Since 2000, there has been a significant increase in women’s average bra cup size from B to E; women with cup sizes D and above are considered “full-busted”. Most commercially available sport bras are designed for low- to medium-impact activities for women with cup size C or smaller, leaving women with cup sizes of D or larger without adequate breast support during physical activity. While the primary source of NSAB pain in these women is likely mechanical, evidence suggests non- mechanical pain pathways that may contribute to pain expression in women. Specifically, evidence of sex- hormone influences, systemic inflammation, and cortical remapping in female animal models with respect to chronic musculoskeletal pain is emerging; however, characterization of the influences of sex-hormone levels, inflammation, and concurrent cortical changes in the somatosensory and motor regions particularly in reference to chronic NSAB pain in women across the lifespan is a major gap in the evidence base. This critical gap in understanding physiological and neurological sex differences in chronic NSAB pain manifestation in full- busted women will be filled by our proposed project. In this project, we will evaluate a non-pharmacological (mechanical) intervention to alleviate NSAB pain in full-busted women and investigate non-mechanical pathways associated with chronic NSAB pain in women. We will measure both self-reported and objective measures of pain in conjunction with objective measures of behavior and blood-based measures to assess: (1) the impact of the mechanical intervention and (2) non-mechanical factors contributing to chronic musculoskeletal pain in women. The findings from this project will advance multifactorial understanding of pain in full-busted women, an underserved and understudied population that lives with chronic musculoskeletal pain. This project aligns with OWH objectives and priorities in advancing science for the health of women and the mission of NIAMS to better understand and treat conditions resulting in pain and chronic degeneration of the musculoskeletal system. With better understanding, interventions can be designed to address pain experienced by women worldwide.