The role of the brain stem in GWVI pathology

海湾战争退伍军人病（GWVI）的特点是多种慢性症状，包括广泛的疼痛 和睡眠障碍这个项目将集中在脑干结构和白色物质通路， 具体联系下丘脑，导水管周围灰质和蓝斑（沿着下丘脑-垂体- 肾上腺轴），并研究其在调节与GWVI相关的疼痛和睡眠障碍中的作用。我们 假设GWVI与已知特定脑干白色物质回路和核团的损伤有关 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， 具体来说为了检验GWVI疼痛调节缺陷的新假设，我们将另外使用 条件性疼痛调制（CPM），以评估由一种刺激的下行疼痛调制的功效。 有害的外周刺激我们的发现很有可能转化为新的治疗试验， 有几种新的候选干预措施可以靶向这些脑干， 结构. 我们的假设将在一项观察性研究中进行测试，该研究比较了50名GWVI退伍军人和50名非GWVI退伍军人。 海湾战争时期（GWE）退伍军人。在筛选、确认合格性并同意所有 退伍军人将接受为期两天的评估。第1天将包括一组认知/功能测试和一个 条件性疼痛调制（CPM）测试。第2天，将对每例患者进行MRI检查， 将完成剩余的认知/功能测试。两次访视间隔不超过一周。这 4-一年的提案将包括100名参与者（2组，每组50人），并在 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.