PROJECT SUMMARY/ABSTRACT Millions of Americans spend each day in severe pain associated with arthritis. The longer the pain persists, the harder it is to treat. Efficacious strategies to manage and prevent chronic pain are needed. A major barrier to chronic pain prevention is a gap in knowledge about how acute joint pain leads to changes in central nervous system (CNS) pathways responsible for sensing, transmitting, and regulating pain. This process is termed pain centralization. The long-term goal of this research program is to enable patients with arthritis and musculoskeletal diseases to function physically, cognitively, and emotionally without impairment from chronic pain. The objective of this STAR award is to identify brain pathways associated with the development of chronic pain in patients with rheumatoid arthritis (RA). The focus of this application is on patients who have had symptoms of RA for less than 12 months. The rationale for this is based on preliminary data from the Canadian Early Arthritis Cohort showing that the incidence of fibromyalgia, the prototypical centralized pain condition, is highest during the first year after RA diagnosis. Thus, it is hypothesized that the first 12 months after RA diagnosis may represent a critical time during which the acute to chronic pain transition may be prevented. Therefore, the specific aims of this STAR award are to: 1) identify neurotransmitters in the brain that will predict the development of chronic pain during the first year after RA symptom onset, and 2) identify measures of the microstructural integrity of nerve fibers in the brain that will predict the development of chronic pain in the first year after RA symptom onset. To assess neurotransmitter levels, proton magnetic resonance spectroscopy will be performed on a subgroup of 80 participants undergoing magnetic resonance imaging as a part of Aim 3 of the parent R01. Proton magnetic resonance spectroscopy is a non-invasive test for measuring biochemical changes in the brain. To assess the microstructural integrity of the nerve fibers in the brain, diffusion tensor imaging will be performed on the same subgroup of 80 participants. Diffusion tensor imaging is a brain imaging technique that measures the magnitude and direction of water molecule movements in the nerve fibers of the brain. The proposed research is innovative because it represents a substantive departure from the status quo by: 1) focusing on early RA, 2) incorporating two novel brain imaging methods that drill down to the level of specific neurotransmitters and nerve fiber tracts (as opposed to larger brain regions, typically assessed by structural and functional magnetic resonance imaging), and 3) employing a multimodal approach, including patient-reported measures of pain, objective assessments of pain sensitivity, and brain imaging, to assess pain pathways. The proposed research is significant because it will enable us to expand our research program by rigorously im...