Functional Dyspepsia: Defining Central Circuits

描述(由候选人提供)： 本申请表是一项名为“功能性消化不良-定义中枢回路”的以病人为导向的研究事业发展奖的申请书。这项工作的长期目标是了解在正常人和功能性消化不良患者中涉及胃感觉的中枢神经机制。拟议的研究项目将对正常人和功能性消化不良患者进行功能磁共振成像(FMRI)研究，这些受试者接受各种类型的胃刺激。消化不良是一种以上腹部不适为特征的状况，是初级保健就诊的最常见原因之一。功能性消化不良的患者有慢性上腹部不适，没有结构性病因。到目前为止，神经成像还没有提供与其他内脏器官和躯体神经系统相比在胃感觉中重要的特定神经回路中的激活细节。本申请提出了三个关于胃感和功能性消化不良的重要问题：1)在有胃刺激的正常人中，利用fMRI信号定义不同的初级内脏传入疼痛通路，并将这些区域与初级躯体刺激的fMRI信号区分开来。2)确定正常人和消化不良患者中枢初级感觉、自主神经和内源性止痛环的fMRI信号对胃刺激的反应是否不同。3)应用药物调节剂，检测功能性消化不良患者中枢神经系统对胃刺激的反应，探讨自主神经系统在慢性内脏痛中的作用。这一职业发展奖将使郭博士在功能成像技术以及内脏疼痛生物学方面获得更多的研究技能和经验，增强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.