Project Summary Chronic musculoskeletal (MSK) pain problems increase dramatically in the adolescent years, with wide impact and high direct and indirect healthcare costs. Unfortunately, adolescents with chronic MSK pain are likely to become adults with chronic MSK pain, and also suffer from high levels of negative consequences, including disability, poor quality of life, and poor psychosocial functioning. In the adolescent developmental period, acute MSK pain complaints (most commonly spine, knee, and foot or ankle pain) account for a large portion of physician visits, and recent studies estimate that about 30-35% of these youth transition from acute pain to a chronic pain state. However, mechanisms underlying the transition from acute to chronic pain states are poorly understood, particularly in adolescents. While there are a number of known biopsychosocial risk factors for the development of chronic pain, better mechanistic understanding of transition between acute and chronic pain states is crucial for the development of novel therapeutics and preventative interventions designed to stop chronic pain before it becomes disabling and costly. The proposed study will examine both key neurobiological and biopsychosocial risk factors that contribute to the development of chronic MSK pain in adolescents. To our knowledge, this would be the first neuroimaging study conducted in a sample of youth presenting for treatment for acute MSK pain. Capturing treatment-seeking adolescents with MSK pain and following these youth over the course of the following year, will provide novel information about candidate mechanisms and risk for the transition from acute to chronic pain states. Using resting state and task-based functional and structural magnetic resonance imaging, alongside comprehensive self and proxy report measures of biopsychosocial history and function, we will identify independent multimodal neurobiological components associated with acute MSK pain and examine associations with theoretically-grounded biopsychosocial risk pathways for chronic pain in the context of a host of environmental factors. We will then prospectively examine how these neurobiological and biopsychosocial risk pathways (pain processing, mood, and pain related cognition) are related to pain persistence and pain-related impact over time using parallel process latent growth curve modeling, as well as retrospectively identify additional state) neurobiological phenotypes (beyond those associated with the acute MSK pain that differentiate individuals demonstrating pain persistence from those with symptom remission. Participants will include adolescents, ages 11-17, with n=200 acute MSK pain and a sample of n=80 age- and sex-matched pain-free controls, as well as a participating parent. These adolescents will be followed an additional three times (every 3 months over a 1 year period) to examine pain persistence and pain-related impacts over time. Determining mechanisms and moderators...