Pain in PASC – The Role of Sleep Disturbances

项目摘要 高达80%的SARS-CoV-2感染者继续经历持续性和衰弱 症状持续3个月以上，也称为急性SARS-CoV-2后遗症 （PASC）或“长COVID”。疼痛是最常见的症状之一，在6个月后仍然存在。 初始感染，沿着睡眠障碍、疲劳和认知障碍。高流行率 病毒感染后的并发症令人担忧迫切需要了解疾病机制， 确定治疗靶点。到目前为止，诸如初始感染的严重程度、医疗合作、 发病率或年龄并不能充分解释谁会发生PASC，谁不会。我们假设 睡眠障碍是PASC疼痛发展和不缓解的关键因素。电流 研究强烈表明，睡眠支持维持无痛状态和最佳功能， 中枢疼痛处理通路。拟议中的工作将是第一个特点的相互关系 PASC患者睡眠障碍与疼痛之间的关系。 20例PASC患者（PCR确诊SARS-CoV-2），10例PCR确诊 感染但未发生PASC（PASC+和PASC-），将纳入本研究（>18岁， 50%女性）。一个全面的疼痛测试和睡眠评估方法，包括在家里和在- 实验室主观和客观监测方法将用于实现以下目标： 目标1将描述PASC+与PASC-相比的疼痛特征。我们将日复一日地观察。 在家庭环境中的自发/持续疼痛，和（B）使用 在住院临床研究中心（CRC）访视期间进行定量体感测试（QST）。我们将 评估触觉、温暖、压力、热和冷等躯体感觉方式的功能状态，以及 作为中枢神经系统（CNS）调节疼痛的能力。 目标2：将解决睡眠障碍指标之间的关联性和方向性的强度 和PASC中的自发性疼痛/躯体感觉功能。睡眠障碍的指标将是 通过（a）在家庭环境中对睡眠进行基于日常日记和活动记录的监测进行评估，以及 (b)多导睡眠图（PSG）在医院环境中评估宏观和微观结构睡眠 特色 这项工作将是第一项研究，探讨睡眠障碍的作用， PASC中的疼痛未消退。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PASC疼痛的第一干预措施。 慢性疼痛的发生。

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.