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.

Figure 1

A photomicrograph of an oesophageal biopsy section from the inflamed oesophageal epithelium from a subject with reflux oesophagitis stained for PGP. The luminal surface is indicated (s). The papillae (p) extend into the epithelium (e). Immunofluorescent staining is seen in the subepithelial plexus extending across the upper poles of most of the papillae (arrow). Original magnification ×200.

Figure 2

(A) Photomicrograph of an oesophageal biopsy section from control tissue stained for VIP. The luminal surface is indicated (s). The papillae (p) extend into the epithelium (e). There are no nerves staining positive for VIP in this biopsy specimen. (B) Photomicrograph of an oesophageal biopsy section from the inflamed oesophageal epithelium of a subject with reflux oesophagitis stained for VIP. The papillae (p) extend into the epithelium (e). Immunofluorescent staining is seen in the subepithelial plexus extending across the upper poles of most of the papillae (arrow). Original magnification ×200.