Carpometacarpal Osteoarthritis: Understanding the Intersection of Muscle Mechanics, Joint Instability, and Pain - PROJECT SUMMARY Individuals with thumb carpometacarpal osteoarthritis (CMC OA) can lose up to 50% of hand function. Unfortunately, current conservative and surgical treatments do not provide the pain relief, strength, and mobility needed to restore both fine and gross motor function. Improvements in clinical treatments are limited by a lack of understanding regarding the complex relationship between thumb biomechanics and musculoskeletal pain. In this proposal, we address this critical knowledge gap by examining the role of thumb muscles in modulating the two primary symptoms of CMC OA: pain and joint instability. Individuals across the full spectrum of disease severity and healthy controls will be studied to evaluate individuals who present with only joint instability, only pain, both, or neither. In Aim 1, to what extent muscle structure changes in the presence of CMC OA and how these changes affect muscle force-generating capacity will be evaluated. Collected data will include fascicle length and cross-section area measured in vivo through ultrasound imaging and thumb muscle operating ranges calculated through musculoskeletal simulations. Completion of this aim will identify changes in muscle structure that mitigate versus aggravate CMC OA symptoms and also establish baseline data describing healthy targets for thumb muscle force-generating parameters. In Aim 2, how thumb muscle activity influences pain will be examined through an experiment that integrates biomechanical techniques (e.g., electromyography) and quantitative pain testing (e.g., movement-evoked pain, quantitative sensory testing). Completion of this aim will enhance our understanding the relationship between muscle activity and pain, thereby elucidating protective versus detrimental compensatory movement strategies adopted by individuals with CMC OA. In Aim 3, how thumb muscle activity influences joint stability will be examined. Collected data will include experimental measurements of muscle activity, thumb kinematics, and thumb kinetics during functional and range of motion tasks as well as biomechanical assessments of joint instability in the presence of active versus passive muscle contraction. Completion of this aim will identify how CMC OA and muscle activity influences CMC joint stability, thereby informing clinical decisions regarding how muscles should (or should not) be considered during CMC OA treatment. Overall, this study will critically advance our mechanistic understanding of how the structure and function of thumb muscles change in the presence of CMC OA. By evaluating muscle mechanics (Aim 1), pain (Aim 2), and joint stability (Aim 3) in individuals with and without CMC OA, we will elucidate the co-evolution of muscle mechanics, symptom severity, and disease severity. This knowledge will inform current and future treatment of CMC OA, thereby improving the quality of life of individuals living with this disease.