Esophageal mucosal innervation in functional heartburn: Closer to healthy asymptomatic subjects than to non‐erosive reflux disease patients

• Published in: Neurogastroenterology and motility Vol. 31; no. 9; pp. e13667 - n/a
• Main Authors: Nikaki, Kornilia, Woodland, Philip, Lee, Chung, Ghisa, Matteo, Marinelli, Carla, Savarino, Edoardo, Sifrim, Daniel
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2019
• Subjects: Barrett's esophagus; Calcitonin gene-related peptide; Esophagitis; Esophagus; Fibers; functional heartburn; Gastroesophageal reflux; Heart; Innervation; Mucosa; Nerves; non‐erosive gastroesophageal reflux disease; oesophageal mucosa innervation; Pain perception; Sensory neurons; non-erosive gastroesophageal reflux disease; oesophageal mucosa innervation; functional heartburn
• ISSN: 1350-1925; 1365-2982; 1365-2982
• DOI: 10.1111/nmo.13667

Background Mucosal innervation in non‐erosive reflux disease (NERD; pathological esophageal acid exposure, normal macroscopic mucosa) is clearly distinct from that of healthy volunteers (HV) and from patients with esophagitis or Barrett's esophagus: The nerves in NERD are situated much closer to the luminal surface of the mucosa. Patients with functional heartburn (FH) have a similar symptom profile to patients with NERD and indistinguishable macroscopic appearances. However, they have physiological acid exposure and no reflux‐symptom association. The aim of our study was to delineate the position of esophageal mucosal nerve fibers in patients with FH and compare it with that in NERD and HV. Methods Distal esophageal biopsies from patients with FH were immunohistochemically stained for CGRP. CGRP‐positive nerve fibers were identified, and their position relative to the lumen was determined. These results were compared to our previously published cohort of HV and NERD. Results Eleven patients were included in the FH group with a mean age of 46 years (range 33‐69); 7F:4M. Nine patients had visible nerve fibers. The location of the afferent nerve fibers in the distal esophageal mucosa (median of 22, range 10.4‐28) was similar to the HV group (median 25.5) and significantly deeper than the superficial nerves seen in NERD (median 9.5). Conclusions The mucosal innervation pattern in FH is more alike that of healthy individuals than that of NERD, with afferent nerves lying deep in the mucosa, away from the luminal surface. This supports the theory that heartburn in FH has a distinct nociceptive pathophysiology. The pathogenesis of heartburn in patients with functional heartburn is unknown and distinct to that of non‐erosive reflux disease. The esophageal mucosa afferent nerves are as deep as in healthy individuals.