The role of the brain stem in GWVI pathology

海湾战争退伍军人病(GWVI)以多种慢性症状为特征，包括广泛的疼痛 以及睡眠障碍。该项目将专注于脑干结构和白质通路， 特异地连接下丘脑、中脑导水管周围灰质和蓝斑(沿着下丘脑-垂体- 肾上腺轴)，并研究它们在调节与GWVI相关的疼痛和睡眠障碍中的作用。我们 假设GWVI与已知的特定脑干白质回路和核团的损害有关 调节疼痛信号和睡眠-觉醒周期，导致这些关键功能的失调。我们 提出最先进的脑成像技术来评估脑干纤维的完整性和体积变化 并将这些成像测量与GWVI相关的疼痛和睡眠测量相关联， 具体地说。为了测试GWVI中痛觉调制缺陷的新假说，我们还将使用 条件性疼痛调制(CPM)评价A刺激下行疼痛调制的疗效 有害的外周刺激。将我们的发现转化为新的治疗试验是非常有可能的 有几种新的候选干预措施可以使这些脑干成为靶点 结构。 我们的假设将在一项观察性研究中得到验证，该研究比较了50名GWVI退伍军人和50名非 有症状的海湾战争(GWe)退伍军人。经过筛选，确认资格，并同意所有 退伍军人将接受为期两天的评估。第一天将包括一系列认知/功能测试和 条件性疼痛调制(CPM)试验。在第二天，将对每个患者进行MRI检查，并 剩余的认知/功能测试将完成。两次访问的间隔不会超过一周。这 为期4年的提案将包括100名参与者(2组，每组50人)，结果衡量标准收集在 适当的时间点。

Gulf War Veterans’ Illness (GWVI) is characterized by multiple chronic symptoms including wide-spread pain and sleep disturbances. This project will focus on brainstem structures and white matter pathways that specifically link the hypothalamus, periaqueductal gray and locus coeruleus (along the hypothalamic-pituitary- adrenal axis), and investigate their role in modulating pain and sleep disturbances associated with GWVI. We hypothesize that GWVI is associated with damage of specific brainstem white matter circuits and nuclei known to modulate pain signaling and sleep-wake cycles resulting in dysregulation of these critical functions. We propose state-of-the-art brain imaging techniques to assess the brainstem fiber integrity and volume changes of key brainstem nuclei and correlate these imaging measures with GWVI-related pain and sleep measures, specifically. To test the novel hypothesis of pain modulation deficits in GWVI, we will additionally use conditioned pain modulation (CPM) to evaluate the efficacy of descending pain modulation stimulated by a noxious peripheral stimulus. The translation of our findings into new therapeutic trials is very probable given that there are several novel candidate interventions that would allow the targeting of these brainstem structures. Our hypotheses will be tested in an observational study comparing 50 GWVI Veterans and 50 non- symptomatic Gulf War era (GWE) Veterans. After screening, confirmation of eligibility, and consenting all Veterans will undergo a 2-day assessment. Day 1 will comprise a battery of cognitive / functional tests and a conditioned pain modulation (CPM) test. On Day 2, MRI exams will be performed on each patient and the remaining cognitive/functional testing will be completed. Both visits will be no more than one week apart. This 4-year proposal will include 100 participants (2 groups of 50 each) with outcome measures collected at appropriate time points.