PROJECT SUMMARY/ABSTRACT Carpometacarpal osteoarthritis (CMC OA) is a disabling disease that can cause severe pain, decreased strength, and limited range of motion. These factors lead to a loss in quality of life and contribute to other concomitant conditions such as decline in mental. Unfortunately, there are no current treatments that will stop the progression of OA or restore both fine and gross motor function. Understanding the pathophysiology of OA is critical to developing improved treatment options that can eliminate pain without compromising physical function. This proposal broadly aims to understand compensatory mechanisms by identifying the relationship between movement and pain. The objective of this work is to compare pain thresholds, muscle control strategies, and joint kinematics between patients with end-stage CMC OA and age-matched healthy adults. Quantitative sensory testing will be used to measure pain thresholds (Aim 1). These results will provide us with a pain baseline, identify pain phenotypes associated with symptomatic OA-pain and whether CMC OA causes sensitization to other parts of the body. Intramuscular electrodes will be used to measure muscle activity and quantify the neuromuscular compensations (Aim 2). These results will highlight how muscle control strategies change to prevent further pain or injury and could inform whether muscles need to be considered during surgical treatments. Motion capture will measure joint angles during range of motion tasks to quantify the effect of pain on movement (Aim 3). The results will highlight how neighboring joints adapt to compensate for disease-induced movement limitations and could inform physical therapy exercises to prevent further restrictions. To further highlight the importance of integrating pain measurements in biomechanical studies, movement-evoked pain measurement (Aim 2 and 3) will emphasize how movement affects pain. The results will create the foundation to supplement future studies examining disease progression or assessing the efficacy of current treatments. Above all, understanding the compensatory mechanisms and the complex nature of pain is the first step to developing improved treatments and targeted therapies. Through this proposal, the applicant will obtain training on teaching and mentoring effectively, collaborating on interdisciplinary teams, and disseminating research to both scientific and clinical audiences. The applicant will also gain experience designing and performing experiments that involve human subjects and using musculoskeletal modeling to complement the experimental results. These experiences will enhance the applicant’s technical and professional skills, thereby providing the training needed for a successful career in academia as research faculty.