Pain in PASC – The Role of Sleep Disturbances

项目总结 高达80%的感染SARS-CoV-2的人继续经历持续和虚弱的经历 持续感染后3个月的症状，也称为急性SARS-CoV-2后遗症 (PASC)或“Long COVID”。疼痛是最常见的症状之一，在术后6个月仍然存在 最初的感染，伴随着睡眠障碍、疲劳和认知障碍。流行性感冒的高患病率 病毒感染后的并发症令人担忧。迫切需要了解疾病的发病机制和 确定治疗目标。到目前为止，一些因素，如最初感染的严重程度，医疗合作 疾病或年龄不能充分解释谁会患上PASC，谁不会。我们假设 睡眠障碍是PASC疼痛发展和无法缓解的关键因素。当前 研究有力地表明，睡眠支持无痛状态的维持和大脑 中枢痛觉处理通路。拟议的工作将是第一个表征相互关系的工作 PASC患者睡眠障碍与疼痛之间的关系。 20例PASC患者(聚合酶链式反应确诊为SARS-CoV-2)和10例聚合酶链式反应确诊患者 感染但未发展为PASC(PASC+和PASC-)，将纳入本研究(&gt；18岁， 女性占50%)。全面的疼痛测试和睡眠评估方法，包括在家中和在- 将使用实验室主观和客观监测方法来实现以下目标： 目的1比较PASC+和PASC-的疼痛特征。我们将(A)监测日常情况 家庭环境中的自发/持续疼痛，以及(B)使用以下方法评估躯体感觉缺陷 在医院临床研究中心(CRC)就诊期间进行定量躯体感觉测试(QST)。我们会 评估身体感觉形式的功能状态，如触摸、温暖、压力、热和冷 作为中枢神经系统(CNS)调节疼痛的能力。 目标2：将探讨睡眠障碍指标之间的关联性和方向性 和PASC的自发性疼痛/躯体感觉功能。睡眠障碍的指标将是 通过以下方式进行评估：(A)对家庭环境中的睡眠进行日常日记和活动监测； (B)在医院环境中进行多导睡眠图(PSG)，以评估宏观和微观结构的睡眠 特点。 这项拟议的工作将是第一次探索睡眠障碍在持续性和非睡眠障碍中的作用。 PASC中的疼痛不能解决。所获得的知识有可能影响治疗策略 旨在使PASC的疼痛正常化，包括解决睡眠困难作为预防 慢性疼痛在这一患者群体中的发展。

PROJECT SUMMARY Up to 80% of individuals infected with SARS-CoV-2 continue to experience persistent and debilitating symptoms that extend >3 months into the post infection period, also called post-acute SARS-CoV-2 sequela (PASC) or ‘long COVID’. Pain is among the most common symptoms remaining after 6 months following the initial infection, along with sleep disturbance, fatigue, and cognitive impairment. The high prevalence rates of post-viral complications are alarming. There is an urgent need to understand the disease mechanisms and identify therapeutic targets. To date, factors such as the severity of the initial infection, medical co- morbidities, or age do not sufficiently explain who develops PASC and who does not. We hypothesize that sleep disturbance is a critical factor in the development and non-resolution of pain in PASC. Current research strongly indicates that sleep supports maintenance of a pain-free state and optimal functioning of central pain processing pathways. The proposed work will be the first to characterize the inter-relationship between sleep disturbance and pain in PASC patients. Twenty patients with PASC (PCR confirmed diagnosis of SARS-CoV-2), and 10 who had PCR confirmed infection but did not develop PASC (PASC+ and PASC-), will be included in this research (>18 years of age, 50% females). A comprehensive pain testing and sleep assessment approach consisting of at-home and in- laboratory subjective and objective monitoring methodologies will be used to address the following aims: Aim 1 will characterize pain in PASC+ compared with PASC-. We will (a) monitor day-to-day spontaneous/ongoing pain in the at-home environment, and (b) assess somatosensory deficits using quantitative somatosensory testing (QST) during the in-hospital Clinical Research Center (CRC) visit. We will evaluate the functional status of somatosensory modalities of touch, warmth, pressure, heat, and cold, as well as the capacity of the central nervous system (CNS) to modulate pain. Aim 2: will address the strength of association and directionality between indicators of sleep disturbance and spontaneous pain/somatosensory functioning in PASC. Indicators of sleep disturbances will be assessed by (a) day-to-day diary- and actigraphy-based monitoring of sleep in the at-home environment, and (b) polysomnography (PSG) in the in-hospital environment to evaluate macro- and microstructural sleep characteristics. The proposed work will be the first study to explore the role of sleep disturbance in the persistence and non-resolution of pain in PASC. Knowledge gained has the potential to influence therapeutic strategies aimed at normalizing pain in PASC, including addressing sleep difficulties as a first intervention to prevent the development of chronic pain in this patient population.