NOCICEPTION IN BULIMIA NERVOSA

神经性贪食症的伤害感受

• 批准号: 7605970
• 负责人: PATRICIA L FARIS
• 金额: $ 0.19万
• 依托单位: UNIVERSITY OF MINNESOTA
• 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 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605970
• 关键词: Behavior; Binge Eating; Bulimia; Chronic; Clinical Data; Clinical Pharmacology; Clinical Treatment; Cognitive Therapy; Computer Retrieval of Information on Scientific Projects Database; Condition; Detection; Disease; Double-Blind Method; Drops; Eating Disorders; Evaluation; Functional disorder; Funding; Grant; Hyperactive behavior; Institution; Methods; Nociception; Ondansetron; Pain; Pain Threshold; Patients; Physiological; Placebo Control; Placebos; Production; Psychophysiology; Randomized; Recruitment Activity; Research; Research Personnel; Resources; Role; Satiation; Severities; Severity of illness; Source; Symptoms; Testing; Therapeutic; United States National Institutes of Health; Vagus nerve structure; Vomiting; Week; afferent nerve; base; indexing; neurotransmission; pill

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. This research (funded by R01 DK 42291-06-09) proposes to further study the role of vagal afferents in the perpetuation of binge-eatinig and vomiting. We previously proposed that the pathophysiology of bulimia nervosa involves dysregulation of the afferent vagus nerve. To date, we have evaluated vagal involvement in this eating disorder using two main strategies: (1) the use of somatic pain detection as a physiological marker of vagal afferent activity; and (2) the use of ondansetron(a 5 HT3 antagonist known to reduce vagal neurotransmission) as a pharmacological challenge test of vagal modulation of both the bulimic behaviors and on elevated pain detection thresholds. The principle findings from these studies are:(1) pain detection thresholds rise dynamically across the interval between bulimic binge/vomit episodes, apparently reaching their zenith as the next bulimic episode is approached and dropping to their nadir in close temporal association with having recently engaged in a bulimic episode; and (2) ondansetron treatment was associated with a significant moderation in both the cyclic fluctuations in pain detection thresholds and the primary disorder symptom of binge/vomit episodes per week in a group of patients with severe and chronic bulimia nervosa under randomized, placebo controlled, double-blind conditions. Collectively, the above summarized physiological and clinical data have led to the refined hypothesis that the pathophysiology of bulimia nervosa involves a cyclic hyperactivity in vagal afferent nerves. The present research proposes to test the hypothesis that cyclic increases in vagal activity drive the binge eating and vomiting through an interactive combination of clinical pharmacology and psychophysiological approaches. The primary aim of the clinical treatment study is to compare the efficacy of ondansetron to cognitive behavioral therapy (CBT) as a function of illness severity. Subjects will be recruitted into two groupsbased on symptom severity (2-<7 episodes per week; 7 or more episodes per week). Within a severity group, patients will be randomly assigned o one of four treatment groups: cognitive behavioral therapy (CBT) plus pill placebe (CBT+Placebo), ondansetron alone (ONDAN), CBT with concomitant ondansetron (CBT+ONDAN) and pill placebo (PLAC) alone. We propose to utilize the gCRC facilities for conducting the initial evaluation of patients being recruited into this study. The primary aim of the psychophysiological study is to investigate the effect of CBT versus ondansetron treatment on physiological indices of vagal activity, namely thresholds for pain detection and induction of satiety. The approach of this Aim is based on the idea that if vagal hyperactivity represents the critical factor involved in symptom production, then any therapeutic method resulting in a decrease in symptoms would be predicted to be accompanied by a demonstrable correction in vagal function. We propose to utilize the gCRC facilities to conduct tests of meal-induced satiety.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这项研究（由R01 DK 42291-06-09资助）提议进一步研究迷走神经传入在暴饮暴食和呕吐持续性中的作用。我们先前提出，神经性贪食症的病理生理涉及传入迷走神经的失调。迄今为止，我们使用两种主要策略评估了迷走神经参与：（1）将躯体疼痛检测用作迷走神经活动的生理标志物； （2）使用ondansetron（已知降低迷走神经传递的5 HT3拮抗剂）作为对鸡不受干扰行为的迷走神经调节和疼痛检测升高的药理挑战测试。这些研究的原则发现是：（1）疼痛检测阈值在大贪食狂/呕吐发作之间的间隔中动态上升，显然是在接近下一个鼠标发作的情况下达到了它们的天顶，并在临时伴随着最近与最近发生的夜间相关性降低了他们的nadir； （2）在一组随机，安慰剂控制，双盲型条件下，一组严重和慢性贪食症的神经性严重和慢性贪食症患者在疼痛检测阈值中的环状波动和狂风/呕吐发作的主要疾病症状都与每周狂热/呕吐发作的主要疾病症状有关，这与ondansetron的治疗均显着适度有关。总体而言，上述摘要的生理和临床数据导致了一个精致的假设，即神经性贪食症的病理生理学涉及迷走神经神经的环状多动症。本研究建议检验以下假设：迷走神经活动的环状增加通过临床药理学和心理生理方法的互动组合促进了暴饮暴食和呕吐。临床治疗研究的主要目的是将ondansetron与认知行为疗法（CBT）的功效进行比较。受试者将在症状严重程度（每周2- <7集；每周7次或以上）的两组中招募。在严重性组中，将随机分配四个治疗组之一：认知行为疗法（CBT）加药物Place（CBT+安慰剂），单独的Ondansetron（Ondan），CBT，与Ondansetron（CBT+Ondan）和placsbo（Placs）相同的CBT。我们建议利用GCRC设施对正在招募的患者进行初步评估。心理生理研究的主要目的是研究CBT与Ondansetron治疗对迷走神经活性的生理指标的影响，即用于疼痛检测和诱导饱腹感的阈值。该目标的方法是基于这样的观念：如果迷走神经多动症代表症状产生的关键因素，那么任何导致症状减少的治疗方法都将伴随着迷走神经功能的明显校正。我们建议利用GCRC设施进行饮食引起的饱腹感测试。