Esophageal sensation and esophageal hypersensitivity - overview from bench to bedside

Abstract

Noxious stimuli in the esophagus activate nociceptive receptors on esophageal mucosa, such as transient receptor potential, acid-sensing ion channel and the P2X family, a family of ligand-gated ion channels responsive to ATP, and this generates signals that are transmitted to the central nervous system via either spinal nerves or vagal nerves, resulting in esophageal sensation. Among the noxious stimuli, gastric acid and other gastric contents are clinically most important, causing typical reflux symptoms such as heartburn and regurgitation. A conventional acid penetration theory has been used to explain the mechanism of heartburn, but much recent evidence does not support this theory. Therefore, it may be necessary to approach the causes of heartburn symptoms from a new conceptual framework. Hypersensitivity of the esophagus, like that of other visceral organs, includes peripheral, central and probably psychosocial factor-mediated hypersensitivity, and is known to play crucial roles in the pathoegenesis of nonerosive reflux disease, functional heartburn and non-cardiac chest pain. There also are esophagitis patients who do not perceive typical symptoms. This condition is known as silent gastroesophageal reflux disease. Although the pathogenesis of silent gastroesophageal reflux disease is still not known, hyposensitivity to reflux of acid may possibly explain the condition.

Keywords: Gastroesophageal reflux; Heartburn; Hypersensitivity; Hyposensitivity; Pain receptor.

Figure 1

Sensory pathway from esophagus to brain. Esophageal nociceptive stimuli are conveyed to the brain via 2 major sensory pathways - a sympathetic pathway and vagal pathway.

Figure 2

Dilated intercellular spaces (DIS). Electron micrographs of esophageal mucosa from a rat with experimental esophagitis (prepared by method of references 65 and 66) and a sham-operated rat. DIS are clearly visible in the mucosa from the experimental esophagitis rat, and are seen only in the deep layer of the mucosa.