The Neurobiological Mechanisms Of Peripheral And Central Sensitization For Esophageal Visceral Hypersensitivity In Patients With Nonerosive Reflux Disease

Background & Aims:Nonerosive reflux disease (NERD) is a very common disease that accounts for 65% to 70% of patients with gastroesophageal reflux disease (GERD). Despite the high prevalence, the mechanisms for the pain, its clinical characteristics, and the optimal therapeutic approach remain poorly understood. Patients' quality of life are affected heavily and a large quantity of medical resources is occupied unnecessarily. The most consistent and common clinical finding in functional esophageal disorders patients is the presence of an increased responsiveness to GI stimulation (named as visceral hypersensitivity), which is considered as an important biological marker of the condition and altered visceral perception to chemical and mechanical stimulation may result from central sensitization. However, the role of visceral hypersensitivity in the etiology and pathogenesis of different-subset NERD remain unclear and the neurobiological mechanisms involved in esophageal visceral hypersensitivity are poorly understood. Therefore, the aim of human study was to evaluate the role of esophageal visceral hypersensitivity in the pathogenesis of different-subset NERD and to investigate the role of substance P(SP) and calcitonin gene-related peptide(CGRP) of Lower esophageal sphincter(LES) mucosa in the peripheral sensitization of visceral hypersensitivity, to observe the characteristics of esophagus innervation with transmission electron microscope(TEM), to evaluate the characteristics and differences of cortical evoked potentials (CEPs) evoked by esophageal distension and acid perfusion in functional heartburn(FH) and controls, and to provide increasing evidence of the involvement of dysfunction of visceral neural pathways and abnormal cortical processing in mediating esophageal hypersensitivity in FH, to sought to identify central loci and compare the characteristics of activation patterns in response to esophageal acid exposure in different-subset NERD, erosive esophagitis(EE) and controls, and to provide further evidence that the cerebral processing of esophageal visceral pain involves multiple brain...