PROJECT SUMMARY / ABSTRACT OVERALL COMPONENT Chronic musculoskeletal pain is extremely common, and pain is the most common symptom in nearly all rheumatic disorders. However, in all chronic pain conditions there is a tremendous disparity between identifiable damage/inflammation in the periphery – and pain, and classic psychological factors such as mood or catastrophizing explain very little of the variance between pain and objective findings. Many individuals with chronic pain have surgery for this problem and have continued pain despite excellent surgical results, just as many patients with autoimmune disorders continue to have pain after inflammation is well controlled with biologics. We hypothesize that the reason there is such a disparity between pain and other symptoms - and the degree of damage/inflammation in the periphery - is that individuals with chronic musculoskeletal pain display variable degrees of fibromyalgia. The University of Michigan Fibromyalgia CORT proposes that the current 2011 FM Survey Criteria is a surrogate measure of centralized pain, and that higher scores on this measure will be predictive of more pain and other symptoms originating from the central nervous system (CNS). Thus higher scores on this measure will render individuals less responsive to analgesic therapies aimed at peripheral/nociceptive pain (surgery, biologics, opioids). We will demonstrate that this centralized pain phenotype has stereotypical clinical and neurobiological features to FM even when it is co-morbid with other musculoskeletal pain conditions with disparate underlying pain mechanisms: osteoarthritis, rheumatoid arthritis, and carpal tunnel syndrome. Our specific aims are: 1) To demonstrate that the current 2011 FM Survey Criteria serve as a strong surrogate of pain centralization and strongly predict non-responsiveness to therapies generally effective for treating peripherally-based pain, including a) surgery intended to relieve pain (hip arthroplasty, carpal tunnel release), b) administration of a biologic agent to treat an autoimmune disorder (rheumatoid arthritis), and c) acute perioperative administration of opioids; 2) To demonstrate that in all three cohorts individuals with the highest FM scores will have similar neurobiological findings of pain centralization on quantitative sensory testing (QST) and neuroimaging; 3) To develop and pilot test a shorter and more predictive self-report measure of pain centralization; 4) To explore the clinical and mechanistic features of two important subsets of centralized pain: top-down (i.e. previously termed primary FM) vs. bottom-up (i.e. previously termed secondary FM); and 5) To serve as a core national resource for training both researchers and clinicians in contemporary musculoskeletal pain research and care.