Corticotropin-Releasing Factor role in Cyclic Vomiting

促肾上腺皮质激素释放因子在周期性呕吐中的作用

• 批准号: 6530195
• 负责人: B U LI
• 金额: $ 16.6万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6530195
• 关键词: adolescence (12-20); adrenocorticotropic hormone; blood tests; catecholamines; child (0-11); clinical research; clinical trials; corticotropin releasing factor; cortisol; dexamethasone; emesis; gastroenteritis; growth factor receptors; human subject; hypothalamic pituitary adrenal axis; inhibitor /antagonist; migraine; nausea; outcomes research; patient oriented research; questionnaires

DESCRIPTION (provided by applicant): Cyclic vomiting syndrome (CVS) is the most severe recurrent vomiting disorder in humans and is more prevalent than previously appreciated (1 in 50 school-aged children). Although the pathogenesis remains unknown, corticotropin-releasing factor (CRF) is a tenable candidate brain-gut neuroendocrine mediator of vomiting in CVS. CRF has a well-established role in inducing gastric stasis and vomiting in animals and its resulting behavioral, autonomic, endocrine effects resemble those clinical features seen in CVS. The model of CRF-induced emeses may explain the antiemetic utility of dexamethasone during chemotherapy-induced vomiting and migraine headaches. We hypothesize that systemic CRF levels and hypothalamic-pituitary-ad renal (HPA) axis activity are heightened during episodes of CVS and migraine headache especially in those who experience concomitant nausea and vomiting. To provide direct clinical evidence of involvement of CRF pathways in CVS and migraine, we will examine CRF and HPA axis activation (ACTH, cortisol, catecholamines) in subjects with CVS, migraine headaches and controls under three conditions including: 1) when well (i.e. in between episodes), 2) during acute episodes of cyclic vomiting or migraine headaches treated with a saline placebo, and, 3) during acute episodes of cyclic vomiting or migraine headaches in which CRF is treated by dexamethasone. Under each condition, we will establish the diurnal variation of CRF and HPA axis activity and compare them to pediatric controls, both healthy and with non-CVS vomiting (gastroenteritis). In a randomized, double blind, cross-over design, we will examine the effect of dexamethasone on CRF and HPA axis activity, objective signs and subjective GI and migraine headache symptoms. CVS and migraine headaches may ultimately both be disorders involving dysregulation of CRF pathways.

描述（由申请人提供）： 环状呕吐综合征（CVS）是人类中最严重的复发性呕吐障碍，比以前所欣赏的更为普遍（50名学龄儿童中有1个）。尽管发病机理尚不清楚，但皮质激素释放因子（CRF）是CVS中呕吐的孕妇脑肠神经内分泌介质。 CRF在诱导动物胃停滞和呕吐及其由此产生的行为，自主神经，内分泌作用中具有良好的作用，类似于CVS中看到的临床特征。 CRF诱导的EMES的模型可以解释化学疗法引起的呕吐和偏头痛期间地塞米松的抗过敏效用。我们假设在CVS和偏头痛的发作期间，系统性CRF水平和下丘脑 - 垂体 - 肾脏（HPA）轴活动会提高，尤其是在那些经历伴随的恶心和呕吐的人中。为了提供CRF途径参与CVS和偏头痛的直接临床证据，我们将检查CRF和HPA轴激活（ACTH，皮质醇，皮质醇，儿茶酚胺）在患有CVS，偏头痛，偏头痛和对照的受试者中，在三个条件下，包括：1）。安慰剂和3）在循环呕吐或偏头痛的急性发作中，在中塞米松治疗CRF的情况下。在每种条件下，我们将建立CRF和HPA轴活动的昼夜变化，并将其与健康和非CVS呕吐（胃肠炎）进行比较。在随机的双盲，跨界设计中，我们将检查地塞米松对CRF和HPA轴活动，客观体征以及主观GI和偏头痛症状的影响。简历和偏头痛最终可能都是涉及CRF途径失调的疾病。