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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 不宁腿综合征(RLS)是一种睡眠相关的感觉-运动障碍，由休息和不活动引起，通过运动缓解。它涉及到一种强烈的冲动，想要移动腿。有一个很强的昼夜节律模式，症状在晚上变得更糟，到了早上明显缓解。尽管睡眠不佳，但RLS患者没有报告明显的白天嗜睡，尽管他们确实报告了疲劳。这可能表明RLS可能涉及一种代偿性唤醒系统。可能在RLS中调节唤醒的一个潜在候选者是下丘脑泌素。已经发现，在未经治疗的RLS患者中，尤其是在早发性RLS患者(症状在45岁之前开始)的患者中，下丘脑泌素水平升高。众所周知，下丘脑泌素系统通过对组胺系统的作用来诱导唤醒。值得注意的是，一些RLS患者的轶事报道称，抗组胺药物会加剧RLS的症状。该研究的目的是检验以下假设：1)抗组胺药物苯那曲引起的RLS症状(PLMW和症状的主观报告)比镇静剂量的劳拉西潘要大得多；2)与晚发RLS患者相比，早发RLS患者服用苯那君后RLS症状的增加更大；3)目前正在治疗的RLS患者夜间脑脊液中下丘脑/食欲素的浓度将比以前报道的未经治疗的RLS患者低；4)在目前正在接受多巴胺能药物治疗的RLS患者中，脑脊液下肌酸将与警醒程度直接相关，与嗜睡程度相反。