Neuromodulation of the Brain-Gut Axis by Transcutaneous Vagal Nerve Stimulation in Functional Dyspepsia

功能性消化不良经皮迷走神经刺激对脑肠轴的神经调节

基本信息

批准号：
9756375
负责人：
VITALY NAPADOW
金额：
$ 25.28万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9756375
关键词：
Affect American Amygdaloid structure Animals Anterior Area Autonomic Dysfunction Biochemical Brain Brain Stem Brain imaging Brain region Burn injury Cell Nucleus Cerebrovascular Circulation Clinical Cross-Over Studies Databases Devices Disease Distress Dyspepsia Effectiveness Electric Stimulation Epigastric Equilibrium Eructation Etiology Exhibits External Ear Frequencies Functional Gastrointestinal Disorders Functional Magnetic Resonance Imaging Functional disorder Galvanic Skin Response Gastric Emptying Gastrointestinal Diseases Goals Human Hypothalamic structure Impairment Insula of Reil Intervention Investigation Link Liquid substance Measures Mediating Modeling Nature Nausea and Vomiting Nerve Neuraxis Operative Surgical Procedures Outcome Pain Pathogenesis Patients Peripheral Pharmaceutical Preparations Pharmacology Process Quality of life Randomized Recurrence Reporting Resistance Rome Sampling Severities Signal Pathway Signal Transduction Single-Blind Study Spin Labels Stomach Structure Subgroup Symptoms Syndrome Techniques Technology Thalamic structure Therapeutic Upper digestive tract structure Vagus nerve structure brain abnormalities cingulate cortex daily functioning dorsal motor nucleus early satiety gut-brain axis heart rate variability implantation improved indexing insight midbrain central gray substance motility disorder multimodality neuroimaging neurophysiology neuroregulation novel novel therapeutics nucleus ambiguus patient population rectal response side effect surgical risk

项目摘要

ABSTRACT Functional Dyspepsia (FD) is a common functional gastrointestinal disorder that affects millions of Americans every year. Symptoms include recurrent epigastric discomfort consisting of any one or a combination of postprandial fullness, early satiation, and/or epigastric pain or burning, in the absence of a clear structural etiology. Some patients with FD are particularly bothered by postprandial fullness and early satiation, a hallmark of the Postprandial Distress Syndrome (PDS) subtype. These symptoms can be particularly debilitating, leading to impaired daily functioning and decreased quality of life. Despite the negative impact these symptoms have on patients' lives, the pathogenesis of PDS-predominant FD (PDS-FD) is not well understood, although it has been postulated that dysregulation of the brain-gut axis driven by abnormal brainstem vagal neurocircuitry is a possible culprit. The current mainstay of treatment for PDS-FD is pharmacological intervention which is, at best, modestly effective. Moreover, in some severe cases, symptoms become intractable, medication causes unwanted side effects and/or patient becomes treatment resistant. However, given the strong link between FD symptoms and compromised vagal function we propose a non- invasive approach that targets the auricular branch of the vagus nerve via transcutaneous vagal nerve stimulation (tVNS) delivered to the cymba conchae of the external ear. Thus, auricular tVNS may provide a novel therapeutic strategy to modulate aberrant brain-gut signaling in PDS-predominant FD. In the current project, we use gastric/autonomic measures combined with multimodal neuroimaging techniques to interrogate the peripheral and central nervous system changes that accompany neuromodulation of brain-gut axis signaling by auricular tVNS in PDS-FD patients during a prandial challenge. The proposed study will contribute new insights into the pathophysiology underlying PDS-FD as well as evaluate the fidelity of novel, non-invasive neuromodulatory techniques such as auricular tVNS to mitigate FD symptoms.

抽象的功能性消化不良 (FD) 是一种常见的功能性胃肠道疾病，影响数百万美国人每年。症状包括反复出现的上腹不适，包括以下任何一种或多种症状的组合：餐后饱胀、早饱和/或上腹疼痛或烧灼感，缺乏明确的结构病因学。一些 FD 患者特别担心餐后饱腹感和早饱感，这是餐后应激综合征 (PDS) 亚型的标志。这些症状可能特别使人衰弱，导致日常功能受损和生活质量下降。尽管有负面影响这些症状对患者的生活有影响，PDS为主的FD（PDS-FD）的发病机制尚不清楚可以理解，尽管人们推测脑肠轴的失调是由异常引起的脑干迷走神经回路可能是罪魁祸首。目前 PDS-FD 的主要治疗方法是药物干预最多只能起到一定的效果。此外，在一些严重的情况下，症状变得棘手，药物会导致不必要的副作用和/或患者对治疗产生抵抗力。然而，鉴于 FD 症状与迷走神经功能受损之间存在密切联系，我们提出了一种非通过经皮迷走神经靶向迷走神经耳支的侵入性方法刺激（tVNS）传递到外耳的耳甲。因此，耳廓 tVNS 可以提供调节 PDS 为主的 FD 中异常脑肠信号传导的新治疗策略。在在当前的项目中，我们使用胃/自主神经措施结合多模式神经影像技术来询问伴随脑肠神经调节的周围和中枢神经系统的变化 PDS-FD 患者在膳食挑战期间通过耳廓 tVNS 进行轴信号传导。拟议的研究将为 PDS-FD 的病理生理学提供新的见解，并评估新颖的保真度，非侵入性神经调节技术，如耳穴 tVNS，可减轻 FD 症状。