Mechanisms of Esophageal Pain

食管疼痛的机制

基本信息

批准号：
7469553
负责人：
JYOTI N SENGUPTA
金额：
$ 17.6万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-15 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7469553
关键词：
ASIC channel Acids Acute Address Afferent Neurons Aftercare Angiography Animals Cardiac Characteristics Chemicals Chest Pain Chronic Classification Clinical Condition Coronary Coronary artery Development Disease Dose Esophageal Esophageal Diseases Esophagitis Esophagus Esthesia Evaluation Exhibits Fiber Glutamate Receptor Goals Hyperalgesia Hypersensitivity In Vitro Investigation Ion Channel Mechanics Modality N-Methylaspartate Neurons Neuropeptide Receptor Nociception Numbers Pain Pathway interactions Patients Pattern Peripheral Physiological Production Property Proteins Recording of previous events Reflux Research Proposals Response to stimulus physiology Role Sensory Signal Transduction Spasm Specificity Spinal Spinal nerve structure Stimulus Symptoms TAC1 gene Tachykinin Receptor Testing Thinking United States Visceral Work allodynia alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid amino 3 hydroxy 5 methylisoxazole 4 propionate attenuation drug development insight mRNA Expression receptor research study response sensory mechanism spinal pathway

项目摘要

DESCRIPTION (provided by applicant): Non-cardiac chest pain (NCCP) is a common functional esophageal disorder, with chronic unexplained symptoms without any identified structural disease. The pain is presumed to be of esophageal origin and is characterized by episodes of unexplained pain that are usually midline. The pain is easily confused with cardiac angina or pain from other esophageal disorders. About 15% - 30% of angiograms performed in chest pain patients are normal, and a coronary artery spasm rarely explains the symptoms. In United States, at least 500,000 coronary angiograms are performed annually for chest pain; NCCP may be present in 75,000 to 150,000. Physiologic mechanisms of underlying symptom production are poorly understood. Most of the available clinical information is from the patient that seeks treatment after the development of symptoms. Therefore, for most part the basic mechanisms that initiate the symptoms remain unknown. Often NCCP is associated with long history of acid reflux without development of esophagitis. It is thought that the hypersensitivity in NCCP could be due to sensitization of peripheral and/or central sensory neurons. The major goal of this research proposal is to understand peripheral sensory mechanisms of esophageal pain under normal physiological condition and during acute and chronic acidification of the esophagus. Electrophysiological and pharmacological studies will be undertaken to understand the roles of sensory neurons in pain and attenuation of their responses, respectively. The proposed specific aims involve systematic characterization of responses of vagal and spinal sensory afferent fibers to mechanical, thermal and chemical stimuli before and after acidification. The study will mainly focus to understand the contribution of cationic channels (ASICs, VR1/TRPV1 and CMR1), ionotropic glutamate receptors (NMDA and AMPA) and neurokinin receptors (NK1, NK2 and NK3) in neuroplastic changes of these neurons in acute and chronic acid exposure. The proposed work is a thorough investigation of peripheral mechanism of esophageal hypersensitivity and pain. The study will provide a valuable information about the adequate stimuli and response characteristics of the primary sensory afferent fibers and the manner in which their altered patterns contribute to visceral hyperalgesia and allodynia. Pharmacological study will provide insight in drug development in management of esophageal pain.

描述（由申请人提供）：非心源性胸痛（NCCP）是一种常见的功能性食管疾病，具有慢性不明原因症状，没有任何已确定的结构性疾病。疼痛被认为是食管起源的，其特征是不明原因的疼痛发作，通常发生在中线。这种疼痛很容易与心绞痛或其他食管疾病引起的疼痛混淆。对胸痛患者进行的血管造影大约有 15% - 30% 是正常的，冠状动脉痉挛很少能解释这些症状。在美国，每年至少有 500,000 例因胸痛而进行的冠状动脉造影； NCCP 可能有 75,000 至 150,000 人。人们对潜在症状产生的生理机制知之甚少。大多数可用的临床信息来自出现症状后寻求治疗的患者。因此，在大多数情况下，引发症状的基本机制仍然未知。通常，NCCP 与长期胃酸反流病史相关，但未发展为食管炎。据认为，NCCP 中的超敏反应可能是由于外周和/或中枢感觉神经元的敏化所致。本研究计划的主要目标是了解正常生理条件下以及食管急性和慢性酸化期间食管疼痛的外周感觉机制。将进行电生理学和药理学研究，以分别了解感觉神经元在疼痛及其反应减弱中的作用。所提出的具体目标涉及系统表征迷走神经和脊髓感觉传入纤维在酸化前后对机械、热和化学刺激的反应。该研究将主要关注阳离子通道（ASIC、VR1/TRPV1和CMR1）、离子型谷氨酸受体（NMDA和AMPA）和神经激肽受体（NK1、NK2和NK3）在这些神经元急性和慢性神经塑性变化中的贡献。酸暴露。拟议的工作是对食管过敏和疼痛的外周机制进行彻底研究。该研究将提供有关初级感觉传入纤维的充分刺激和反应特征以及它们的改变模式导致内脏痛觉过敏和异常性疼痛的方式的有价值的信息。药理学研究将为治疗食管疼痛的药物开发提供见解。