Oesophageal epithelial innervation in health and reflux oesophagitis

Abstract

Background-The response of the oesophagus to refluxed gastric contents is likely to depend on intact neural mechanisms in the oesophageal mucosa. The epithelial innervation has not been systematically evaluated in health or reflux disease. Aims-To study oesophageal epithelial innervation in controls, and also inflamed and non-inflamed mucosa in patients with reflux oesophagitis and healed oesophagitis. Patients-Ten controls, nine patients with reflux oesophagitis, and five patients with healed oesophagitis. Methods-Oesophageal epithelial biopsy specimens were obtained at endoscopy. The distribution of the neuronal marker protein gene product 9.5 (PGP), and the neuropeptides calcitonin gene related peptide (CGRP), neuropeptide Y (NPY), substance P (SP), and vasoactive intestinal peptide (VIP) were investigated by immunohistochemistry. Density of innervation was assessed by the proportion of papillae in each oesophageal epithelial biopsy specimen containing immunoreactive fibres (found in the subepithelium and epithelial papillae, but not penetrating the epithelium). Results-The proportion of papillae positive for PGP immunoreactive nerve fibres was significantly increased in inflamed tissue when compared with controls, and non-inflamed and healed tissue. There was also a significant increase in VIP immunoreactive fibres within epithelial papillae. Other neuropeptides showed no proportional changes in inflammation. Conclusions-Epithelial biopsy specimens can be used to assess innervation in the oesophagus. The innervation of the oesophageal mucosa is not altered in non-inflamed tissue of patients with oesophagitis but alters in response to inflammation, where there is a selective increase (about three-to fourfold) in VIP containing nerves. (Gut 1999;44:317-322)

Cardiac autonomic dysfunction in patients with gastroesophageal reflux disease

“…Inflammation of the esophageal mucosa affects local receptors that may induce afferent-efferent reflex mechanisms of the cardiac rhythm, which can lead to secondary stimulation of the vagal nerves inducing the cardiac dysrhythmias [18] . Propagation of the local inflammatory process through the esophageal wall may also cause local pericarditis or atrial myocarditis [19] . Other reports, however, have suggested a strong association between esophageal acid exposure and neurocardiac dysfunction in patients with reflux symptomatology.…”

From Reflux Esophagitis to Esophageal Adenocarcinoma

“…It is thought that the sensation of heartburn is conveyed by the visceral sensory neurons that reside within the deep layers of the esophageal mucosa [9]. These visceral sensory neurons respond to hydrogen ions and other inflammatory mediators via the expression of chemosensitive nociceptors such as the acid-sensing ion channel 3 (ASIC3) and the transient receptor potential vanilloid receptor 1 (TRPV1), which are thought to trigger the generation of heartburn symptoms [10].…”

Atrial Fibrillation and Acid Reflux Disease

“…19 Inflammation of the esophageal mucosa affects local receptors that may induce afferent-efferent reflex mechanisms of the cardiac rhythm, which can lead to secondary stimulation of the vagal nerves inducing AF. 20 This relationship has been shown to be particularly strong among younger patients and athletes who have been found to have increased vagal tone. 7 Propagation of the local inflammatory process through the esophageal wall may also cause local pericarditis or atrial myocarditis.…”