Effects of Insomnia on Pain & Function in Osteoarthritis:The Role of Inflammation

描述（由申请人提供）：骨关节炎（OA）是美国功能性残疾的主要原因，影响65岁以上成年人的一半。然而，疼痛和身体功能通常与关节病理学的放射学指标相关性很差。需要研究阐明与症状表达相关的因素，这些因素有助于开发新的预防和管理策略。慢性失眠是一个可能的因素，发生在约50%的膝关节OA患者中，但对OA失眠的后果、机制和管理知之甚少。我们的实验工作表明，睡眠障碍可能是慢性疼痛的危险因素和后果，睡眠中断直接改变中枢疼痛处理。这些疼痛处理的变化放大了疼痛感知，我们假设它们可能有助于疼痛的持续性及其在OA中有害的身体和情感后果。该辅助提案增强了我们正在进行的骨关节炎睡眠项目[SOAP（R 01 AR 054871）]，这是一项对四组特征良好的老年人进行的大规模研究：匹配的健康对照组和伴或不伴失眠的膝关节OA患者。母项目包括一项临床试验，以确定睡眠障碍是否会损害OA的中枢疼痛处理和调节，使用科学定量感觉测试方法，并确定失眠的认知行为疗法（CBT-I）是否改善OA的短期和长期睡眠和临床疼痛。基于新兴的睡眠和疼痛研究，我们假设在这个辅助建议，异常炎症活动可能代表一种常见的神经生物学机制，睡眠中断有助于疼痛增强，身体限制和情绪障碍。为了验证这一假设，我们将在母研究中纳入：a）静息和疼痛诱发炎症的评估; B）一组简短的标准化体能测试; c）日常身体功能的非侵入性测量（活动记录仪）; d）疼痛诱发和日常情绪障碍的正式评估。该辅助建议的具体目的是：1）表征老年人中静息和疼痛诱发的炎症与疼痛、身体功能和情绪障碍之间的复杂相互关系; 2）确定OA和/或失眠是否与静息和疼痛诱发的炎症的升高相关;和3）确定CBT-I是否减少静息和疼痛诱发的炎症，以及炎症的变化是否介导患有失眠症的OA患者的疼痛、身体功能和情绪的改善。失眠和炎症都可以通过行为和药物治疗来改变。因此，拟议的项目很可能产生的结果，将有一个新的和实质性的影响，预防，管理和治疗骨关节炎。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is the leading cause of functional disability in the United States, impacting half of adults over the age of 65. Pain and physical function, however, are often poorly associated with radiographic measures of joint pathology. Research clarifying the factors associated with symptom expression that contribute to the development of novel prevention and management strategies is needed. Chronic insomnia is one likely factor, which occurs in ~50% of knee OA patients, but the consequences, mechanisms and management of insomnia in OA is poorly understood. Our experimental work indicates that sleep disturbance may be both a risk factor for and a consequence of chronic pain, and that sleep disruption directly alters central pain processing. These pain processing changes amplify pain perception, and we hypothesize they may contribute to pain persistence and its detrimental physical and emotional consequences in OA. This ancillary proposal enhances our ongoing Sleep in Osteoarthritis Project [SOAP (R01AR054871)], a large-scale investigation of four well-characterized groups of older adults: matched healthy controls and knee OA patients with and without insomnia. The parent project includes a clinical trial to determine whether sleep disturbance impairs central pain processing and modulation in OA, using state-of-the-science quantitative sensory testing methods, and determines whether cognitive behavioral therapy for insomnia (CBT-I) improves short and long-term sleep and clinical pain in OA. Based on emerging sleep and pain research, we hypothesize in this ancillary proposal that aberrant inflammatory activity may represent a common neurobiologic mechanism by which sleep disruption contributes to pain augmentation, physical limitations and mood disturbance. To test this hypothesis, we will integrate into the parent study: a) assessments of resting and pain-evoked inflammation; b) a brief battery of standardized physical performance tests; c) unobtrusive daily measurements of physical function (actigraphy); and d) formal assessments of pain-evoked and daily mood disturbance. The Specific Aims of this ancillary proposal are to: 1) characterize the complex inter- relationships between resting and pain-evoked inflammation and pain, physical function and mood disturbance in older adults; 2) determine whether OA and/or insomnia are associated with elevations in resting and pain-evoked inflammation; and 3) determine whether CBT-I decreases resting and pain-evoked inflammation, and whether changes in inflammation mediate improvements in pain, physical function and mood in OA patients with insomnia. Both insomnia and inflammation are modifiable via behavioral and pharmacologic therapies. Therefore, the proposed project is likely to generate findings that will have a novel and substantial impact on the prevention, management and treatment of OA.