Defining Adolescent Nausea through Brain-Gut Physiology and Neurostimulation Response

通过脑肠生理学和神经刺激反应定义青少年恶心

基本信息

批准号：
10395620
负责人：
Katja Kristina Karrento
金额：
$ 17.06万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
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：
2018-07-25 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10395620
关键词：
Abdominal Pain Adolescent Affect Amygdaloid structure Animals Anxiety Area Arousal Autonomic nervous system Brain Brain Stem Brain region Child Childhood Clinical Complex Cranial Nerves Development Devices Diagnostic Diagnostic tests Disease Dizziness Down-Regulation Electric Stimulation Emotional Equilibrium Esthesia External Ear Feeling suicidal Functional Gastrointestinal Disorders Functional Magnetic Resonance Imaging Functional disorder Gastric Emptying Gastroenterologist Gastroenterology Gastroparesis Heat Exhaustion High Prevalence Human Hyperalgesia Hypothalamic structure Impairment Irritable Bowel Syndrome Knowledge Label Learning Measures Mediating Mentored Patient-Oriented Research Career Development Award Modality Morbidity - disease rate Motor Nausea Nerve Nervous System Physiology Neurologist Neurons Outcome Output Pain Pain Disorder Pathway interactions Patients Peripheral Pharmaceutical Preparations Physiological Physiology Placebos Play Prefrontal Cortex Psychologist Psychophysiologic Disorders Public Health Quality of life Questionnaires Randomized Rest Safety Satiation Schools Signal Transduction Stomach Subcategory Subgroup Symptoms Techniques Testing Time Training Visceral affective disturbance base brain pathway cell motility common symptom comorbidity disability effective therapy efficacy testing falls functional disability heart rate variability improved indexing motility disorder motor disorder neural circuit neuroimaging novel novel therapeutics patient population pediatrician prospective psychologic reduce symptoms response side effect social treatment response

项目摘要

PROJECT SUMMARY The high prevalence, reduced quality of life and poor understanding of functional gastrointestinal disorders calls for development of better diagnostic modalities and novel therapies. Functional nausea (FN) is a particularly challenging subcategory as there is no knowledge of mechanisms to direct therapy. Due to close symptom overlap, patients with FN fall between the cracks of several subspecialties and other better defined disorders. Disorders of gastric motor function such as delayed stomach emptying (gastroparesis) and impaired gastric compliance share very similar symptom complex and are difficult to distinguish from FN based on available tests in children. The common co-occurrence of anxiety results in labeling many with undefined nausea with psychosomatic disease. Our prior descriptive studies point to autonomic nervous system (ANS) imbalance and high arousal in adolescents with “functional nausea.” Central brain pathways and the arousal neurocircuitry are closely integrated with ANS signals. The main purpose of this study is to investigate brain- gut mechanisms at play in adolescents with FN and the efficacy of a novel neurostimulation device for nausea. Two aims are proposed in this K23 award. The first aim attempts to classify nausea into defined subtypes based on clinical and physiologic parameters (gastric motor abnormalities and autonomic imbalance). No prior study has prospectively described pediatric FN. We will classify FN based on autonomic imbalance/low vagal tone and lack of gastric motor dysfunction. We will use non-invasive gastric function tests to categorize patients and heart rate variability measures as an index of autonomic balance/vagal tone to further define FN. The second aim focuses on response to neurostimulation therapy and hypothesized functional brain connectivity changes in patients with FN. Our group has recently demonstrated the ability to modulate central brain pathways in animals with a peripheral, non-invasive neurostimulation device. This novel, FDA-cleared neurostimulation device delivers percutaneous, electrical stimulation below sensation threshold to branches of several cranial nerves including the vagus, in the external ear. In animals, this therapy inhibits amygdala output and improves visceral hyperalgesia. In humans, we have shown safety and efficacy over placebo for adolescents with functional abdominal pain disorders. A subset with improvement in concurrent nausea had a notable increase in vagal tone with therapy. We hypothesize that neurostimulation improves FN by modulating ANS function and limbic brain areas (amygdala, hypothalamus). We will investigate vagal tone and functional brain connectivity changes induced by this therapy compared to baseline and healthy controls. Through this proposal, we hope to gather more knowledge on the brain-gut pathways underlying functional nausea and study a novel therapy with strong physiologic basis for this debilitating condition.

项目概要患病率高、生活质量下降以及对功能性胃肠道疾病了解甚少呼吁开发更好的诊断方式和新疗法。特别具有挑战性的子类别，因为不知道指导治疗的机制。症状重叠，FN 患者介于几个亚专业和其他更明确的亚专业之间胃运动功能障碍，例如胃排空延迟（胃轻瘫）和受损。胃顺应性具有非常相似的症状复合体，并且很难根据 FN 与 FN 区分儿童中常见的焦虑同时发生导致许多人被贴上不确定的标签。我们之前的描述性研究指出，恶心与心身疾病有关。患有“功能性恶心”的青少年的不平衡和高度唤醒。神经回路与 ANS 信号紧密结合。这项研究的主要目的是研究大脑。患有 FN 的青少年的肠道机制以及新型神经刺激装置治疗恶心的功效。 K23 奖项提出了两个目标，第一个目标试图将恶心分为定义的亚型。基于临床和生理参数（胃运动异常和自主神经失衡）。研究前瞻性地描述了儿童 FN。我们将根据自主神经失衡/低水平对 FN 进行分类。迷走神经张力和缺乏胃运动功能障碍我们将使用非侵入性胃功能测试来分类。患者和心率变异性测量作为自主平衡/迷走神经张力的指标，以进一步定义 FN。第二个目标侧重于对神经刺激疗法的反应和挖掘功能性大脑我们的研究小组最近证明了调节中枢的能力。这种新颖的、经 FDA 批准的神经刺激装置可用于动物的大脑通路。神经刺激装置向神经分支提供低于感觉阈值的经皮电刺激在动物的外耳中，这种疗法会抑制杏仁核的输出，包括迷走神经。并改善内脏痛觉过敏，在人类中，我们已经显示出比安慰剂更安全和有效的效果。患有功能性腹痛疾病的青少年的并发恶心有所改善。通过治疗，迷走神经张力显着增加。我们勇敢地说，神经刺激可以通过调节来改善 FN。 ANS 功能和边缘脑区域（杏仁核、下丘脑）我们将研究迷走神经张力和功能。与基线和健康对照相比，这种疗法引起的大脑连接变化。建议，我们希望收集更多关于功能性恶心和肠胃潜在功能性恶心的知识研究一种针对这种令人衰弱的疾病具有强大生理基础的新疗法。