Mechanisms of Esophageal Pain

食管疼痛的机制

• 批准号: 6919339
• 负责人: JYOTI N SENGUPTA
• 金额: $ 18.94万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 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/6919339
• 关键词: afferent nerve; chemical stimulation; electrophysiology; esophagus; gastrointestinal pharmacology; glutamate receptor; heat stimulus; hypersensitivity; immunocytochemistry; laboratory rat; mechanical pressure; membrane channels; neural plasticity; neuropeptide receptor; pain; peripheral nervous system; polymerase chain reaction; reflux esophagitis; western blottings

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）：非心脏胸痛（NCCP）是一种常见的功能性食管疾病，患有慢性无法解释的症状，没有任何发现的结构性疾病。疼痛被认为是食管的起源，其特征是通常是中线的无法解释的疼痛发作。疼痛很容易与心绞痛或其他食道疾病的疼痛混淆。在胸痛患者中进行的血管造影中，约有15％-30％是正常的，冠状动脉痉挛很少解释症状。在美国，每年至少进行500,000个冠状动脉造影术以治疗胸痛。 NCCP可能出现在75,000至150,000中。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症状发展后寻求治疗的患者。因此，在大多数情况下，启动症状的基本机制仍然未知。 NCCP通常与胃酸反流的悠久史有关，而没有食管炎的发展。据认为，NCCP的高敏性可能是由于周围和/或中央感觉神经元的敏化。该研究建议的主要目的是了解在正常生理状况下以及食管急性和慢性酸化期间食管疼痛的外围感觉机制。将进行电生理和药理研究，以了解感觉神经元在疼痛和反应的衰减中的作用。提出的特定目的涉及对迷走神经和脊柱感觉传入纤维对机械，热和化学刺激的反应的系统表征。这项研究将主要集中于了解阳离子通道（ASIC，VR1/TRPV1和CMR1），离子型谷氨酸受体（NMDA和AMPA）以及神经蛋白受体（NK1，NK2和NK3）在这些神经抗性危害和慢性含量中的神经脱位变化中的贡献。拟议的工作是对食道超敏反应和疼痛的外围机制的彻底研究。这项研究将提供有关主要感觉传入纤维的适当刺激和反应特征的有价值信息，以及它们改变的模式有助于内脏的痛觉过敏和异常性的方式。药理学研究将为食管疼痛治疗的药物开发提供洞察力。