Functional Dyspepsia: Defining Central Circuits

描述（由候选人提供）： 此申请是为指导病人为导向的研究职业发展奖题为“功能性消化不良-定义中央电路”。这项工作的长期目标是了解正常人和功能性消化不良患者胃感觉的中枢神经机制。拟议的研究项目将对正常人和接受各种胃刺激的功能性消化不良患者进行功能性磁共振成像研究。消化不良是一种以上腹部不适为特征的疾病，是初级保健就诊的最常见原因之一。功能性消化不良患者有慢性上腹部不适，无结构性病因。到目前为止，神经影像学还没有提供许多细节，在特定的神经回路的激活是重要的胃感觉相比，其他内脏器官以及躯体神经系统。本申请提出了三个目的来解决关于胃感觉和功能性消化不良的重要问题：1）在具有胃刺激的正常人类受试者中利用fMRI信号来定义不同的初级内脏传入疼痛通路，并将这些区域与来自初级躯体刺激的fMRI信号区分开。2)确定正常人受试者与消化不良患者对胃刺激的反应中中枢初级感觉、自主神经和内源性镇痛回路中的fMRI信号是否不同。3)通过应用药理学调节剂和检查功能性消化不良患者对胃刺激的中枢神经系统通路的fMRI信号反应，探讨自主神经系统在慢性内脏痛中的作用。该职业发展奖将使郭博士获得功能成像技术以及内脏疼痛生物学方面的额外研究技能和经验，从而提高他实现成为神经胃肠病学独立研究员的职业目标的能力。

DESCRIPTION (provided by candidate): This application is for a Mentored Patient-Oriented Research Career Development Award entitled "Functional Dyspepsia- Defining Central Circuits". The long-term objective of this work is to understand the central neural mechanisms involved in gastric sensation in the normal human condition and in patients with functional dyspepsia. The proposed research project will conduct functional magnetic resonance imaging (fMRI) studies on normal human subjects and functional dyspeptics undergoing various types of gastric stimulation. Dyspepsia, a condition characterized by upper abdominal discomfort, is one of the most common reasons for primary care visits. Patients with functional dyspepsia have chronic epigastric discomfort without a structural etiology. To date, neuroimaging has not provided many details regarding the activation in specific neural circuits that are important in gastric sensation compared to other visceral organs as well as the somatic nervous system. This application proposes three aims to address important issues regarding gastric sensation and functional dyspepsia: 1) To define distinct primary visceral afferent pain pathways utilizing fMRI signal in normal human subjects with a gastric stimulus and distinguish these regions from the fMRI signal from a primary somatic stimulus. 2) To determine if the fMRI signal in central primary sensory, autonomic, and endogenous analgesic circuits is different in normal human subjects from patients with dyspepsia in response to a gastric stimulus. 3) To interrogate the role of the autonomic system in chronic visceral pain by applying a pharmacological modulator and examining the fMRI signal response in the CNS pathways within a group of patients with functional dyspepsia in response to a gastric stimulus. This career development award will allow Dr. Kuo to acquire the additional research skills and experience in functional imaging techniques as well as in visceral pain biology enhancing his ability to achieve his career goal of becoming an independent researcher in neurogastroenterology.