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

项目摘要/摘要 失眠是一种睡眠障碍，其特征是入睡困难或保持入睡，或两者兼而有之 获得睡眠的机会。因此，失眠症患者可能睡眠过少和/或睡眠不佳。 质量。失眠是艾滋病病毒携带者(PLWH)常见的一种令人衰弱的睡眠障碍， 估计在30%到73%之间。失眠越来越被视为发病和/或恶化的危险因素。 疼痛症状和身体机能缺陷。研究发现，失眠会加剧疼痛 敏感性(也称为痛觉过敏)，这对日常生活中疼痛的病因学至关重要。这是特别的 与PLWH有关，因为最近的证据证明，疼痛症状在 普罗旺斯医院的日常生活。失眠是否是疼痛和身体功能不良的危险因素 到目前为止，PLWH是一个受到关注最少的主题；因此，需要进行额外的研究。 炎症过程是将失眠与疼痛和生理联系起来的重要生物机制。 功能。失眠促进全身炎症以及对身体应激源的炎症反应，如 疼痛。对非艾滋病毒样本进行的研究表明，炎症会显著增加 在实验室环境中对疼痛刺激的敏感性，以及在日常生活和 身体残疾。综上所述，失眠可能通过 炎性介质的增殖。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HIV相关患者的后果和影响 合并症。因此，这项提案的总体目标是调查失眠对疼痛的影响， PLWH的生理功能和炎症。我们将通过解决以下问题来实现总体目标 以下具体目标：1)确定失眠是否促进实验性疼痛敏感性的增加和 PLWH对疼痛刺激的过度炎症反应，以及2)是否决定了失眠的波动 随着时间的推移，负担会导致日常生活中的炎症和疼痛，以及PLWH的身体功能。这些 目标将使用由我们的研究团队开发和严格改进的研究方法来解决，并且 之前已经得出了有希望的初步结果，表明失眠确实可能会促进疼痛和 PLWH中的炎症反应。这种方法是创新的，因为失眠对疼痛和疼痛相关的影响 炎症过程以前从未在PLWH中被直接检查过。此外，成立 客观和主观测量睡眠和身体功能，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这一提议的创新。建议数 研究将具有重要意义，因为如果我们的假设得到证实，我们将确定：1)失眠是一种主要的 PLWH在实验室和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.