Project Summary / Abstract Chronic musculoskeletal (MSK) pain affects the lives of over a quarter of adolescents in the US each year with impacts into adulthood evidenced by lower educational attainment, poor vocational function, social impairments and higher risk for opioid misuse. Progressively increasing activity in the presence of pain is critical for effective functional restoration in chronic MSK pain with physiotherapy (PT) a foundational treatment. Despite the widespread use of PT, daring to increase movement while in pain can often feel physically and emotionally unattainable with fear of pain a particularly salient influence on pain outcomes, hindering clinical improvement. Virtual reality (VR) provides access to a multisensory, three-dimensional (3D) immersive experience that has the potential to break the vicious cycle of fear of movement and avoidance during PT. VR has been suggested as an alternative to opioids with the therapeutic mechanisms centered on distraction, neuromodulation of body perception, and graded exposure to feared/avoided movements. Moreover, VR can potentially enhance motivation and engagement, facilitate repetitive motions, and incorporate real-time and longitudinal feedback for the patient and clinician. From our preliminary data, user-centered iteratively developed Pain Rehabilitation Virtual Reality (PRVR) was deemed highly engaging and increased in-session movement when compared to Standard Physiotherapy Rehabilitation (SPR). Building on this pilot work, the proposed research is a randomized controlled trial of PRVR aimed at measuring changes in physical function and pain-related fear for adolescents with chronic MSK pain when compared to SPR. Aim 1 evaluates physical function (primary outcome) and pain related fear (secondary outcome) between PRVR and SPR. Aim 2 characterizes feasibility of a future hybrid effectiveness-dissemination trial of PRVR in routine PT practice. Significant breakthroughs in the treatment of MSK pain require mechanistically-informed innovative approaches. PRVR harnesses immersive technology to overcome the key barrier of fear of movement in the presence of pain, provides real-time feedback in a gamified context to sustain motivation and adherence, and purposefully captures both objective (kinematics, actigraphy) and subjective (self-report) daily functioning to define clinical endpoints and assess treatment progress in the clinic and at home. These findings will directly inform the decision of whether to proceed with a hybrid effectiveness-dissemination trial of PRVR, serving as the basis for potential large-scale implementation of PRVR.