Slow wave sleep and inflammatory processes in pain

描述（由申请人提供）：骨关节炎（OA），也称为退行性关节疾病，是美国最常见的关节疾病形式，是导致老年人功能障碍和独立性降低的主要原因。对于患有骨关节炎和其他慢性疼痛的老年人来说，睡眠障碍是一个重要的问题，会降低生活质量并增加功能障碍。虽然痛苦 会导致睡眠中断，睡眠障碍同样会增加疼痛感。我们的长期目标是确定导致慢性疼痛和睡眠障碍之间双向关联的心理神经生物学机制。最近的疼痛和睡眠心理神经免疫学模型以及我们自己的初步工作强烈表明，由疼痛引起的与压力相关的炎症过程可能在持续性疼痛和睡眠障碍之间的双向关联中发挥关键作用。此外，深度、非快速眼动睡眠，即慢波睡眠（SWS），可能在睡眠不良、炎症和疼痛之间的联系中发挥着特定作用。我们认为，睡眠障碍，尤其是睡眠障碍，会加剧对急性疼痛的炎症反应，降低疼痛阈值，从而导致慢性疼痛和残疾的持久循环。为了对该模型进行概念验证，我们提出了一项研究，旨在检查操纵睡眠对患有膝骨关节炎疼痛和失眠的老年人的炎症和疼痛过程的影响。该 R21 应用的具体目的是检查通过针对失眠的认知行为干预（尤其是 SWS 改善）来改善睡眠是否与响应急性实验室疼痛和临床 OA 疼痛的炎症细胞因子水平和疼痛阈值相关。拟议的研究测试了一个新颖且创新的假设，即慢性睡眠障碍通过增强与压力相关的炎症反应，从而增强慢性骨关节炎疼痛患者的疼痛。通过比较失眠治疗前后对急性疼痛的炎症反应，拟议的研究将检验这样一种观点，即逆转不良睡眠，尤其是睡眠不足，可以减轻慢性疼痛患者的炎症反应。 50 岁及以上成年人口的不断增长、老年人中 OA 的高患病率、OA 和慢性疼痛的经济负担以及疼痛状况对老年人福祉的有害影响，都要求开发治疗慢性疼痛的新方法。对假设途径的支持将扩展单独的睡眠和疼痛文献，并支持转向更明确地阐述睡眠和疼痛之间的神经炎症联系。这项阐述通过强调睡眠和相关炎症过程作为主要治疗目标，特别是患有 OA 的老年人，具有巨大的潜力，有助于疼痛治疗的发展和临床疼痛实践。 公共健康相关性：该项目旨在确定在慢性疼痛和睡眠障碍之间的关系中发挥作用的生物因素。我们的具体目标是检查患有骨关节炎的老年人睡眠不佳是否与疼痛反应增强的炎症有关，最终导致持续性骨关节炎疼痛。了解睡眠障碍如何影响疼痛有助于制定有效的干预措施来管理慢性疼痛，减少残疾和医疗费用，并改善患有骨关​​节炎等疼痛疾病的老年人的福祉。

DESCRIPTION (provided by applicant): 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.