Osteoarthritis (OA), also known as degenerative joint disease, represents the most common form of joint disorder in the United States and is a large contributor to functional impairment and reduced independence in older adults. For older adults with OA, and with other chronic pain conditions more generally, sleep disturbance is a significant complaint, reducing quality of life and increasing functional disability. Although pain can contribute to disrupted sleep, sleep disturbance can likewise augment pain perception. Our long-term objective is to identify psycho-neurobiological mechanisms contributing to bi-directional associations between chronic pain and sleep disturbance. Recent psychoneuroimmunological models of pain and of sleep, and our own preliminary work, strongly suggest that stress-associated inflammatory processes provoked by pain may serve a critical role in bi-directional associations between persistent pains and sleep disturbance. Further, deep, non rapid eye movement sleep, known as slow wave sleep (SWS), may play a specific role in links between poor sleep, inflammation and pain. We propose that sleep disturbance, especially SWS, exacerbate inflammatory responses to acute pain, diminish pain thresholds, and, thus, contribute to an enduring cycle of chronic pain and disability. To generate proof of concept for this model, we propose a study aimed at examining the effects of manipulating sleep on inflammatory and pain processes in older adults with knee OA pain and insomnia.
The specific aim of this R21 application is to examine whether sleep improvement, via a cognitive behavioral intervention for insomnia, and SWS improvement in particular, is associated with inflammatory cytokine levels and pain thresholds in response to acute laboratory pain, and clinical OA pain. The proposed study tests a novel and innovative hypothesis that chronic sleep disturbance serves as a pain augmenter in individuals with chronic OA pain through its impact on enhancement of stress-related inflammatory responses. By comparing inflammatory responses to acute pain before and after treatment for insomnia, the proposed study will test the notion that reversal of poor sleep, especially SWS, can attenuate inflammatory responses in individuals with chronic pain. The growing population of adults 50 years of age and older, the high prevalence of OA among older adults, the economic burden of OA and chronic pain, and the pernicious impact of pain conditions on older adults'well-being require that new approaches to managing chronic pain are developed. Support for the hypothesized pathway will extend the separate sleep and pain literatures and support a shift toward more explicit elaboration of neuroinflammatory connections between sleep and pain. This elaboration has strong potential to contribute to pain treatment development and clinical pain practices by highlighting sleep and associated inflammatory processes as primary therapeutic targets, especially in older adults with OA.

Public Health Relevance

This project seeks to identify biological factors that play a role in the relationship between chronic pains and sleep disturbance. We aim specifically to examine whether poor sleep in older adults with osteoarthritis is associated with enhanced inflammation in response to pain that, ultimately, contributes to persistent osteoarthritis pain. Understanding how sleep disturbance influences pain can contribute to the development of effective interventions to manage chronic pain, reduce disability and health care costs, and improve well-being in older adults with painful conditions like osteoarthritis.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Exploratory/Developmental Grants (R21)
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Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
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Mackiewicz, Miroslaw
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University of Rochester
Schools of Dentistry
United States
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Heffner, Kathi L; France, Christopher R; Ashrafioun, Lisham et al. (2018) Clinical Pain-related Outcomes and Inflammatory Cytokine Response to Pain Following Insomnia Improvement in Adults With Knee Osteoarthritis. Clin J Pain 34:1133-1140