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

• 批准号: 9750766
• 负责人: Katja Kristina Karrento
• 金额: $ 17.71万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-25 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750766
• 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; base; brain pathway; cell motility; common symptom; disability; disturbance in affect; effective therapy; efficacy testing; falls; functional disability; heart rate variability; improved; indexing; motility disorder; motor disorder; neuroimaging; novel; novel therapeutics; patient population; pediatrician; prospective; psychologic; reduce symptoms; response; side effect; social; treatment response

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.

项目摘要 高患病率，生活质量降低和对功能性胃肠道疾病的理解不足 呼吁开发更好的诊断方式和新型疗法。功能性恶心（FN）是 特别是挑战子类别，因为没有直接治疗机制的知识。由于关闭 症状重叠，FN患者在几个亚专业的裂缝和其他更好定义的裂缝之间落在 疾病。胃运动功能的疾病，例如延迟的档位（胃轻瘫）和受损 胃合规性具有非常相似的症状复合物，很难与FN区分开 儿童的可用测试。焦虑的常见同时出现导致许多不确定的标签 患有心身疾病的恶心。我们先前的描述性研究指出了自主神经系统（ANS） “功能性恶心”的青少年中的不平衡和高唤醒。中央大脑通路和唤醒 神经记录与ANS信号紧密集成。这项研究的主要目的是研究大脑 FN的青少年和新型神经刺激装置的效率在恶心的效率中发挥作用。 该K23奖提出了两个目标。第一个目标试图将恶心分类为已定义的亚型 基于临床和生理参数（胃运动异常和自主性失衡）。没有先验 研究前瞻性描述了小儿FN。我们将根据自主不平衡/低的fn分类 迷走神经和缺乏胃电动机功能障碍。我们将使用非侵入性胃功能测试进行分类 患者和心率变异性度量作为自主平衡/迷走神经音调的指数，以进一步定义FN。 第二个目标重点是对神经刺激疗法和假设的功能性大脑的反应 FN患者的连通性变化。我们的小组最近证明了调节中央的能力 具有外周，非侵入性神经刺激装置的动物的脑途径。这部小说，FDA清理 神经刺激装置在感觉阈值以下传递经皮，电刺激到 外耳中的几种颅神经在内，包括迷走神经。在动物中，这种疗法抑制杏仁核的输出 并改善内脏痛觉过敏。在人类中，我们对安慰剂表现出安全性和效率 功能性腹痛障碍的青少年。具有改善的并发恶心的子集有一个 通过治疗值得注意的迷走神经张力。我们假设神经刺激通过调节来改善FN ANS功能和边缘大脑区域（杏仁核，下丘脑）。我们将研究阴道语调和功能 与基线和健康对照相比，该疗法引起的大脑连通性变化。通过这个 提案，我们希望能收集更多有关功能性恶心和 研究一种具有强大生理基础的新型疗法，以解决这种衰弱的疾病。