Summary To improve our understanding and treatment of chronic musculoskeletal pain, NOT-AR-23-015 calls for an expansion of rheumatic, skin, and musculoskeletal disease pain research. In response to this NOSI, we propose to expand our parent award to evaluate myofascial contributions to chronic OA pain and disability. The parent award - UC2AR082196 - is part of the RE-JOIN Consortium, which has the over-arching goal of defining the sensory innervation of different articular and peri-articular tissues. Within this Consortium-wide goal, the central objective of our parent award is to define shifts in joint innervation patterns and evaluate how these innervation shifts relate to the development of symptomatic joint pain and disability in both preclinical models and patients. In addition to the innervation of joint structures (bone, synovium, cartilage, fibrocartilage), chronic OA pain may be driven by physiologic shifts occurring beyond the joint, including changes in the fascia that lines the extra- articular muscle. Fascia is richly innervated, and pathological changes in the fascia innervation or structure could disrupt sensory information and contribute to OA pain. Our preliminary data using ultrasound imaging support these findings, as variations in fascial thickness, muscle echogenicity and fascia stiffness are associated with greater overall joint pain and worse function in persons with symptomatic knee OA. As such, this supplement application seeks to expand the aims of the parent award by adding new studies on the role of fascia on the development of chronic knee OA. The parent UC2 study provides an extraordinary and time-sensitive opportunity to understand how fascia structure and innervation are related and how pathologic shifts in fascia contribute to OA-related pain and disability in the knee. We propose to test the following hypotheses in data collected from a cohort of knee OA patients, recruited via the parent award: 1) Fascia structure (thickness, composition, stiffness) will vary between individuals with knee OA and OA-free controls and be associated with pain and function; 2) Fascia innervation patterns (sensory) will vary between individuals with knee OA and OA-free controls, and be associated with pain and function; and 3) Fascia structure and innervation patterns will vary across age. These hypotheses will be evaluated using ultrasound imaging of fascia lata (b-mode, shear wave elastography) and analyses of fascia lata biopsies collected at the time of total knee arthroplasty. Patient pain and function will be assessed prior to arthroplasty, as described in the parent award. Combined, these data will allow us to compare clinically-relevant ultrasound images to microstructure changes in the fascia, while relating all of these measures of fascia pathology to quantitative metrics of pain and disability in OA patients.