The Impact of Insomnia on Pain, Physical Function, and Inflammation in HIV

项目概要/摘要 失眠是一种睡眠障碍，其特征是难以入睡，保持睡眠，或两者兼而有之，尽管足够的 获得睡眠的机会。因此，失眠症患者可能睡眠不足和/或睡眠不佳 质量.失眠是艾滋病毒感染者（PLWH）中常见的一种使人衰弱的睡眠障碍， 估计在30- 73%之间。越来越多的人认为胰岛素抵抗是一种发病和/或恶化的风险因素。 疼痛症状和身体功能缺陷的症状。研究发现，肌肉收缩会增强疼痛 敏感性（也称为痛觉过敏），这对日常生活中的疼痛病因至关重要。这是特别 与PLWH相关，因为最近的证据证明，疼痛症状在 PLWH的日常生活失眠是否是疼痛和身体机能不良的风险因素 在PLWH是一个主题，得到了最少的关注日期;因此，需要更多的研究。 炎症过程代表了将失眠与疼痛和身体疾病联系起来的重要生物学机制。 功能胰岛素促进全身炎症以及对物理应激源的炎症反应， 痛苦对非艾滋病毒样本进行的研究表明，炎症可以大大增加 在实验室环境中对疼痛刺激的敏感性，以及在日常生活中加剧疼痛症状， 身体残疾。总之，失眠可能会通过以下方式驱动PLWH的疼痛和身体功能： 炎症介质的增殖。目前有必要阐明的机制和调解人， PLWH的睡眠障碍，以及这些障碍对其他艾滋病毒相关疾病的后果和影响。 合并症。因此，本提案的总体目标是调查失眠对疼痛的影响， PLWH中的身体功能和炎症。我们将通过解决以下问题实现我们的总体目标： 以下具体目的：1）确定失眠是否促进实验性疼痛敏感性的增加， PLWH对疼痛刺激的过度炎症反应，以及2）确定失眠的波动是否 随着时间的推移，负担会导致感染者在日常生活中出现炎症和疼痛，并影响身体功能。这些 目标将使用我们的研究团队开发和严格完善的研究方法来解决， 先前已经取得了有希望的初步结果，表明失眠确实可能会促进疼痛， PLWH中的炎症。这种方法是创新的，因为失眠对疼痛的影响与疼痛有关。 以前从未在PLWH中直接检查过炎症过程。此外， 睡眠和身体功能的客观和主观测量，实验性疼痛测试，以及广泛的 一系列促炎和抗炎生物标志物也有助于该提议的创新。拟议 研究将是重要的，因为，如果我们的假设得到证实，我们将确定：1）失眠是一个主要的 实验室和PLWH日常生活中疼痛和身体功能的驱动因素，以及2）炎症 作为PLWH中与失眠相关的重要疼痛介质。

Project Summary/Abstract Insomnia is a sleep disorder characterized by difficulty falling asleep, staying asleep, or both, despite adequate opportunity for sleep attainment. As a result, people with insomnia may get too little sleep and/or have poor sleep quality. Insomnia is a common and debilitating sleep disorder in persons living with HIV (PLWH), with prevalence estimates ranging from 30-73%. Insomnia is increasingly viewed as a risk factor for the onset and/or worsening of pain symptoms and physical functioning deficits. Insomnia has been found to promote enhanced pain sensitivity (also known as hyperalgesia), which is critical to the etiology of pain in everyday life. This is particularly relevant for PLWH because recent evidence attests to the fact that pain symptoms are quite prevalent in the daily lives of PLWH. Whether insomnia is a risk factor for the experience of pain and poor physical functioning in PLWH is a topic that has received minimal attention to date; therefore, additional research is needed. Inflammatory processes represent an important biologic mechanism linking insomnia to pain and physical function. Insomnia promotes systemic inflammation as well as inflammatory reactivity to physical stressors like pain. Research conducted with non-HIV samples has shown that inflammation can substantially increase sensitivity to painful stimuli in the laboratory setting, as well as exacerbate pain symptoms in everyday life and physical disability. Taken together, insomnia may drive pain and physical function in PLWH through the proliferation of inflammatory mediators. There is currently a need to elucidate mechanisms and mediators of sleep disorders in PLWH, and the consequences and influences of these disturbances on other HIV-related comorbidities. Accordingly, the overall objective of this proposal is to investigate the impact of insomnia on pain, physical function, and inflammation in PLWH. We will accomplish our overall objective by addressing the following specific aims: 1) determine whether insomnia promotes increased experimental pain sensitivity and exaggerated inflammatory reactivity to painful stimuli in PLWH, and 2) determine if fluctuations in insomnia burden over time drive inflammation and pain in everyday life, and physical functioning among PLWH. These aims will be addressed using study methods developed and rigorously refined by our research team, and which have previously yielded promising preliminary results suggesting that insomnia may indeed promote pain and inflammation in PLWH. This approach is innovative because the impact of insomnia on pain and pain-related inflammatory processes has never before been directly examined in PLWH. Furthermore, the incorporation of objective as well as subjective measures of sleep and physical function, experimental pain testing, and a wide array of pro- and anti-inflammatory biomarkers also contributes to the innovation of this proposal. The proposed research will be significant because, if our hypotheses are confirmed, we will identify: 1) insomnia as a major driver of pain and physical functioning in the laboratory and in everyday life among PLWH, and 2) inflammation as an important insomnia-related mediator of pain in PLWH.