Pain is an incredibly common, burdensome, and intractable problem among older adults. It is present in some two-thirds of older adults (a prevalence that is increasing over time), predicts loss of functional independence, is associated with impaired gait and falls, interferes with attention and memory, and was estimated to have an economic cost in the US in 2010 of ~$600 billion – approximately that of heart disease and cancer combined. Given the profound impact of chronic pain in older adults, and the poor options for treating it, better understanding of its determinants is essential. Obesity has long been recognized as a major contributor to chronic pain in older populations, but its mechanism is uncertain. Although the association of obesity with pain is commonly attributed to osteoarthrosis related to chronic excess weight, obesity is associated not only with pain in load-bearing sites like the back and foot but even with pain of the hand. These observations suggest that adiposity has adverse metabolic effects leading to chronic pain well beyond sheer weight alone. Among metabolic effects of obesity, higher levels of non-esterified fatty acids (NEFA) are of particular interest. NEFAs cross the blood-brain barrier and are toxic to both neurons and supporting cells. In previous analyses in the Cardiovascular Health Study (CHS), we have shown that circulating levels of NEFAs are associated with disability and mobility limitation and with a higher likelihood of mental, neurologic, and musculoskeletal hospitalizations. These associations all suggest that NEFAs could have a role in modulating pain. To date, however, the formal relationship of NEFAs with pain has not been evaluated. We propose to use the rich storehouse of data in CHS to evaluate three potential aspects of this relationship – associations with self- reported pain, claims for National Pain Strategy-recommended diagnoses, and peripheral nerve function. CHS is an ongoing cohort study of older adults from four US communities who were evaluated in-person from 1989-1990 to 1998-1999 and have continued to be followed for disability, cardiovascular events, and medical claims. In a previous NHLBI-funded award, we measured NEFA levels in >4,000 participants (and with NIA funding, repeated the measurement at a later visit in ~2,000 participants). In addition, CHS has extremely rich, but currently under-utilized, potential data on chronic pain that we propose to leverage in this supplement. These data include repeated assessments of pain at 7 designated anatomical sites (and an open-ended option), CMS claims for ambulatory and inpatient services, and measurement of vibration sense in both lower extremities. Together, these sources provide a rich, complementary look into NEFAs and pain. Because NEFAs are potentially modifiable pharmacologically, our results may provide qualitative new insights into ways to prevent, reduce, or modulate pain in older adults. This supplement will also make possible...