HYPOCRETIN, HISTAMINE AND THE RESTLESS LEGS SYNDROME

下丘脑分泌素、组胺和不宁腿综合症

• 批准号: 7607466
• 负责人: RICHARD M ALLEN
• 金额: $ 1.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7607466
• 关键词: Age; Antihistamines; Arousal; Circadian Rhythms; Computer Retrieval of Information on Scientific Projects Database; Dose; Fatigue; Funding; Grant; Histamine; Institution; Leg; Lorazepam; Measures; Mediating; Movement; Patients; Pattern; Pharmaceutical Preparations; Purpose; Relative (related person); Reporting; Research; Research Personnel; Resources; Rest; Restless Legs Syndrome; SK-Diphenhydramine; Sleep; Source; Symptoms; System; Testing; United States National Institutes of Health; alertness; early onset; hypocretin; motor disorder

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Restless Legs Syndrome (RLS) is a sleep-related, sensori-motor disorder brough on by rest and inactivity and relived by movement. It involves a compelling urge to move the legs. There is a strong circadian pattern, with symptoms becoming worse at night with marked relief by morning. Despite poor sleep, RLS patients do not report significant daytime sleepiness, although they do report fatigue. This would suggest that RLS may involve a compensatory arousal system. One potential candidate that may mediate arousal in RLS is hypocretin. Hypocretin has been found to be elevated in untreated patients with RLS, particularly in patients with early-onset RLS (in which symptoms begin before age 45). The hypocretin system is known to induce arousal by its actions on the histamine system. Notably, there are anecdotal reports by some patients with RLS that anti-histamines exacerbate the symptoms of RLS. The purpose of this study is to test the following hypotheses: 1) The antihistamine drug, benadryl, will induce RLS symptoms (PLMW and subjective reports of symptoms) significantly more than a sedating dose of lorazepam; 2) The increase in RLS symptoms following Benadryl will be greater for early-onset RLS patients, relative to late-onset RLS patients; 3) Nocturnal CSF of hypocretin/orexin will be lower on patients currently under treatment for RLS than those previously reported in un-treated RLS; 4) In RLS patients currently being treated with dopaminergic medication, CSF hypocretin will correlate directly with measures of alertness and inversely with measures of sleepiness.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 不宁腿综合症 (RLS) 是一种与睡眠相关的感觉运动障碍，由休息和不活动引起，并通过运动缓解。 它涉及移动双腿的强烈冲动。 有很强的昼夜节律模式，症状在晚上变得更严重，到早上明显缓解。 尽管睡眠质量不佳，RLS 患者并没有报告明显的白天嗜睡，尽管他们确实报告有疲劳。 这表明不宁腿综合症可能涉及代偿性唤醒系统。 下丘脑分泌素是一种可能介导 RLS 唤醒的潜在候选者。 研究发现，未经治疗的不宁腿综合征患者的下丘脑分泌素水平升高，尤其是早发性不宁腿综合征患者（症状在 45 岁之前开始）。已知下丘脑分泌素系统通过其对组胺系统的作用来诱导性唤起。 值得注意的是，有一些不宁腿综合征患者的轶事报道称，抗组胺药会加剧不宁腿综合征的症状。 本研究的目的是检验以下假设： 1) 抗组胺药苯海拉明会比镇静剂量的劳拉西泮显着更多地诱发 RLS 症状（PLMW 和症状的主观报告）； 2) 相对于晚发性不宁腿综合征患者，早发性不宁腿综合征患者服用苯那君后，不宁腿综合征症状的增加幅度更大； 3) 目前正在接受不宁腿综合征治疗的患者夜间脑脊液中的下丘脑分泌素/食欲素将低于之前报告的未经治疗的不宁腿综合征患者； 4) 在目前接受多巴胺能药物治疗的不宁腿综合征患者中，脑脊液下丘脑分泌素与警觉性测量值直接相关，与困倦测量值反向相关。