Sleep Disturbance, Central Pain Modulation, and Clinical Pain in Osteoarthritis

描述（申请人提供）：骨关节炎（OA）是世界上最常见的疾病之一，也是导致残疾的主要原因。除了疼痛之外，睡眠障碍是OA更常见和致残的症状之一。大量的纵向研究和一些实验研究表明，虽然睡眠不佳是疼痛的结果，但睡眠障碍也可能干扰反馈，导致痛觉过敏并加剧临床疼痛。慢性疼痛（包括OA疼痛）的最新概念模型涉及调节（放大或抑制）伤害性传递的功能障碍性脊髓上疼痛处理机制。我们小组的初步工作表明，临床相关的睡眠中断直接损害健康个体的这些中枢疼痛处理机制。缺乏对OA睡眠障碍的经验性治疗，也缺乏表明睡眠正常化是否会改变疼痛处理机制和临床疼痛的数据。该提案旨在扩展我们的工作，以调查膝关节OA临床疼痛的神经行为原因和治疗。项目目标是：1）确定睡眠维持性失眠和睡眠的客观多导睡眠图测量与疼痛调节改变相关的程度，和2）评估改善睡眠障碍是否通过改善疼痛调节来减少临床疼痛。提出了两个相互关联的研究。研究1是对有和无失眠的膝关节OA患者与有和无失眠的匹配对照进行析因比较。将比较这4组的睡眠脑电图测量、疼痛调制的实验室指数和临床疼痛评级。研究2是一项随机、双盲、安慰剂对照的临床试验，研究认知行为疗法治疗膝关节OA患者失眠（CBT-I）。来自研究1的符合睡眠维持失眠标准的受试者将被随机分配至经验证的CBT-I方案或标准化行为安慰剂对照组。治疗中途（4周）、治疗后以及3个月和6个月随访时测量的主要终点为：睡眠的客观和主观测量值、疼痛调节的实验室测量值和临床疼痛严重程度。该项目将增加对睡眠障碍增强疼痛敏感性的机制的了解，并为OA失眠症提供急需的经验性非药物治疗方法。骨关节炎影响大约29%的44岁以上的成年人和50%的64岁以上的成年人。疼痛和失眠是与退行性关节疾病相关的两种最常见和致残的症状，它们会导致严重的个人痛苦，并对医疗保健系统和经济造成相当大的负担。该项目将：1）增加对慢性睡眠障碍放大关节炎疼痛的机制的科学理解，2）严格测试关节炎失眠症急需的行为治疗是否不仅改善睡眠，而且反过来减轻疼痛。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is one of the most common diseases and leading causes of disability in the world. Sleep disturbance, in addition to pain, is one of more frequent and disabling symptoms of OA. Numerous longitudinal and some experimental studies indicate that while poor sleep is a consequence of pain, sleep disturbance may also reciprocally feedback to cause hyperalgesia and exacerbate clinical pain. Recent conceptual models of chronic pain, including OA pain, implicate dysfunctional supraspinal pain processing mechanisms that modulate (amplify or inhibit) nociceptive transmission. Preliminary work by our group indicates that clinically relevant sleep disruptions directly impair these central pain processing mechanisms in healthy individuals. Empirical treatments for sleep disturbance in OA are lacking, as are data indicating whether normalization of sleep alters pain processing mechanisms and clinical pain. This proposal seeks to extend our work to investigate neurobehavioral causes and treatments of clinical pain in knee OA. Project aims are to: 1) determine the extent to which sleep maintenance insomnia and objective polysomnographic measures of sleep are associated with alterations in pain modulation and 2) evaluate whether improving sleep disturbance decreases clinical pain by improving pain modulation. Two inter-related studies are proposed. Study 1 is a factorial comparison of knee OA patients with and without insomnia versus matched controls with and without insomnia. These 4 groups will be compared on electroencephalographic measures of sleep, laboratory indices of pain modulation, and clinical pain ratings. Study 2 is a randomized, double-blinded, placebo controlled clinical trial of cognitive-behavior therapy for insomnia (CBT-I) in knee OA. Subjects from Study 1, meeting criteria for sleep maintenance insomnia will be randomized to a validated CBT-I protocol or a standardized behavioral placebo control. Primary endpoints measured half-way through treatment (4 weeks), at post-treatment, and 3 and 6 month follow-ups are: objective and subjective measures of sleep, laboratory measures of pain modulation, and clinical pain severity. This project will increase knowledge of the mechanisms by which sleep disturbance enhances pain sensitivity and lead to a critically needed empirical, non-pharmacological treatment approach for insomnia in OA. Osteoarthritis impacts approximately 29% of adults over the age of 44 and 50% of adults over the age of 64. Pain and insomnia are two of the most common and disabling symptoms associated with degenerative joint disease that cause substantial personal suffering and pose considerable burden on the healthcare system and the economy. This project will: 1) increase the scientific understanding of the mechanisms by which chronic sleep disturbance amplifies pain in arthritis and 2) rigorously test whether a much needed behavioral treatment for insomnia in arthritis not only improves sleep, but in turn reduces pain.