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，影响了一半的65岁以上成年人。然而，疼痛和身体功能通常与关节病理的x线测量相关性很差。需要研究阐明与症状表达相关的因素，从而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，约50%的膝关节OA患者出现失眠，但OA患者失眠的后果、机制和处理尚不清楚。我们的实验工作表明，睡眠障碍可能既是慢性疼痛的风险因素，也是慢性疼痛的后果，睡眠中断直接改变了中枢性疼痛的处理。这些疼痛加工过程的变化放大了疼痛感知，我们假设它们可能有助于OA患者的疼痛持续性及其有害的身体和情绪后果。这一辅助建议加强了我们正在进行的骨关节炎睡眠项目[SOAP (R01AR054871)]，这是一项针对四组老年人的大规模调查：匹配的健康对照组和有或没有失眠的膝关节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中枢性疼痛的加工和调节，使用最先进的定量感觉测试方法，并确定失眠的认知行为疗法（CBT-I）是否能改善OA患者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，我们在这篇辅助提案中假设异常炎症活动可能代表一种常见的神经生物学机制，通过该机制，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，我们将整合母体研究：a)静息和疼痛诱发炎症的评估；B)一系列简单的标准化物理性能测试；C)日常不显眼的身体功能测量（活动记录仪）；d)对疼痛诱发和日常情绪障碍的正式评估。本辅助建议的具体目的是：1)表征老年人休息和疼痛引起的炎症和疼痛、身体功能和情绪障碍之间复杂的相互关系；2)确定OA和/或失眠是否与静息和疼痛诱发炎症升高有关；3)确定CBT-I是否降低了OA失眠患者的静息和疼痛诱发炎症，炎症的改变是否介导了疼痛、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，拟议的项目可能会产生对OA的预防、管理和治疗产生新颖而重大影响的发现。

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.