Non-erosive reflux disease (NERD) is a common and heterogeneous disorder. We hypothesized that changes in peripheral innervation may lead to hyperalgesia and contribute to the development of the disorder.
Patients referred for evaluation of reflux symptoms with wireless pH monitoring were asked to provide demographic and clinical data and complete a survey related to severity of reflux symptoms. Endoscopies were performed to rule out macroscopic abnormalities of the esophageal mucosa. Biopsies obtained 2 cm above the gastroesophageal junction were stained for protein gene product 9.5 (PGP 9.5; general neuronal marker) and TRPV1 (capsaicin receptor) immunoreactivity. The density of immunoreactive fibers in the esophageal mucosa was determined morphometrically.
A total of 39 patients without evidence of Barrett's metaplasia, erosive or ulcerative esophagitis were enrolled. Most patients had daily symptoms. The total esophageal acid exposure time was 5.6±0.6%, with 16 patients (41%) having increased acid reflux. Immunoreactivity for PGP 9.5 or TRPV1 was detected in papillary structures as well as within the epithelium (free intra-epithelial endings). Total acid-exposure time, but not symptom score or duration correlated significantly with density of PGP 9.5 immunoreactivity and TRPV1 positive fibers.
Even in the absence of macroscopic injury, esophageal acid exposure is associated with changes in mucosal innervation of the esophagus, thus potentially further enhancing symptoms in patients with gastroesophageal reflux.
Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh School of Medicine, USA
Correspondence to Dr Klaus Bielefeldt, University of Pittsburgh, Division of Gastroenterology, 200 Lothrop St., Pittsburgh, PA 15213, USA
Tel: +001 412 648 9845; fax: +001 412 648 9731;
Received 24 August 2005 Accepted 16 October 2005