Sleep and circadian rhythm disturbances as risk and progression factors for multiple chronic pain conditions

项目总结 慢性疼痛影响着超过三分之一的美国人口，每年的医疗费用为 1万亿美元。一些经常同时出现的最普遍的“特发性”疼痛症状，如慢性低血压 背痛(CLBP)、颞下颌关节紊乱病和纤维肌痛被称为慢性重叠疼痛 条件(COPC)。在各种慢性前列腺癌中，cLBP的患病率最高，是最常见的10种疾病之一 使世界范围内的条件失效。不幸的是，拥有多个COPC可能会进一步干扰个人的 适应性疼痛应对和加剧疼痛相关的残疾。然而，到目前为止，人们一直将重点放在 个体解剖学上的慢性疼痛状况和/或一次一个COPC，而对此知之甚少 进展为多个COPC的潜在机制。从基于解剖学的方法转变为范式 对于基于机制的方法，识别多个COPC的共同和可修改的风险因素至关重要 在制定有效的干预措施以治疗和预防多发性COPC方面。新出现的证据表明 睡眠和昼夜节律紊乱--COPC的常见临床特征--是可修改的，可能 通过增强疼痛放大和增强在向多个COPC发展过程中发挥重要作用 心理困扰，这是多个COPC的两个关键的近端决定因素。在本研究中， 我们建议招募300名患有慢性腰痛的参与者(即200名仅患有慢性腰背痛的参与者，100名患有慢性腰背痛的参与者)，以及 其他COPC)在基线上。其中，200名仅患有慢性下腰痛的参与者将接受为期12个月的随访。沉睡 而昼夜节律将使用切割法进行纵向(即基线和6个月随访)评估。 EDGE无线脑电睡眠监测仪，24小时评价尿液6-硫氧肌醇节律 (AMT6s)、手腕佩戴的动作记录仪和日常睡眠日记。疼痛放大(通过定量感官测量 测试)、心理痛苦(通过经过充分验证的自我报告测量)以及疼痛的数量 将在基线和6个月和12个月的随访中评估部位(通过经过充分验证的疼痛身体地图进行测量)。 增加访问量。拟议的研究将(1)全面描述睡眠和昼夜节律的严重程度 使用生态有效的多模式动态评估在患有单项和多发性精神疾病的个体中的干扰 多个COPC；(2)前瞻性检查睡眠和睡眠的基线和变化(0至6个月) 昼夜节律紊乱与疼痛放大和心理变化(0至6个月)有关 (3)6个月时是否存在疼痛放大和心理困扰及其变化(6-12岁) 月)与疼痛部位数量的进展(6至12个月)相关(即，有效的替代测量 多个COPC)，同时控制基线睡眠和昼夜节律紊乱的影响。调查结果 这项拟议的工作将为潜在的进展机制提供新的见解 给多个COPC，这些COPC可以为这些具有挑战性的疾病的治疗和预防战略提供信息。

PROJECT SUMMARY Chronic pain affects more than one third of the U.S. population, incurring an annual health care cost of $1 trillion. Some of the most prevalent “idiopathic” pain conditions that frequently co-occur, such as chronic low back pain (cLBP), temporomandibular disorders, and fibromyalgia, are referred to as Chronic Overlapping Pain Conditions (COPCs). Among various COPCs, cLBP has the highest prevalence and is one of the top 10 most disabling conditions worldwide. Unfortunately, having multiple COPCs can further interfere with individuals' adaptive pain coping and exacerbate pain-related disability. However, much focus to date has been placed on individual anatomically-based chronic pain conditions and/or one COPC at a time, while little is known about the mechanisms underlying progression to multiple COPCs. A paradigm shift from anatomy-based approaches to mechanism-based approaches recognizing common and modifiable risk factors of multiple COPCs is crucial in developing effective interventions to treat and prevent multiple COPCs. Emerging evidence suggests that sleep and circadian rhythm disturbances—common clinical features across COPCs—that are modifiable, may serve an important role in progression to multiple COPCs via enhancement of pain amplification and psychological distress, which are two critical proximal determinants of multiple COPCs. For the present study, we propose to recruit a total of 300 participants with cLBP (i.e., 200 with cLBP only vs. 100 with cLBP and other COPCs) at baseline. Among these, 200 participants with cLBP only will be followed for 12 months. Sleep and circadian rhythms will be assessed longitudinally (i.e., baseline and 6-month follow-up) using a cutting- edge wireless EEG sleep monitoring device, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin (aMT6s), wrist worn actigraphy, and daily sleep diaries. Pain amplification (measured by quantitative sensory testing), psychological distress (measured by well-validated self-report measures), and the number of pain sites (measured by a well-validated pain body map) will be assessed at baseline, and 6- and 12-month follow- up visits. The proposed study will (1) comprehensively characterize the severity of sleep and circadian disturbances using ecologically valid multimodal ambulatory assessments among individuals with single and multiple COPCs; (2) prospectively examine whether baseline and changes (0 to 6 months) in sleep and circadian disturbances are associated with changes (0 to 6 months) in pain amplification and psychological distress; and (3) whether pain amplification and psychological distress at 6 months and their changes (6 to 12 months) are related to progression (6 to 12 months) in the number of pain sites (i.e., a valid proxy measure of multiple COPCs), while controlling for the effects of baseline sleep and circadian disturbances. The findings from this proposed work will provide novel insights into potential mechanistic pathways underlying progression to multiple COPCs, which may inform treatment and prevention strategies for these challenging conditions.