Mucosal pathogenesis in gastro-esophageal reflux disease

Ahsen Ustaoglu, Anh Nguyen, Stuart Spechler, Daniel Sifrim, Rhonda Souza, Philip Woodland

Research output: Contribution to journalReview articlepeer-review

25 Scopus citations


Background: Despite gastro-esophageal reflux disease affecting up to 20% of Western populations, relatively little is known about the molecular mechanisms underlying its most troublesome symptom: heartburn. Recent findings have unveiled the role of components of the esophageal mucosa in the pathogenesis of GERD including sensory nociceptive nerves and inflammatory mediators. Erosive esophagitis was long believed to develop as a result of acid injury at the esophageal lumen, but novel concepts suggest the generation of reflux-induced esophageal injury as a result of cytokine-mediated inflammation. Moreover, the localization and characterization of mucosal afferent nerves vary between GERD phenotypes and could explain the heterogeneity of symptom perception between patients who experience similar levels of acid reflux. Purpose: The purpose of this review is to consider the crosstalk of different factors of the esophageal mucosa in the pathogenesis of GERD, with a particular focus on mucosal innervation and molecular basis of acid-induced cytokine response. We discuss the current understanding of the mucosal response to acid injury, the nociceptive role of acid-sensitive receptors expressed in the esophageal mucosa, and the role of esophageal epithelial cells in initiating the onset of erosive esophagitis.

Original languageEnglish (US)
Article numbere14022
JournalNeurogastroenterology and Motility
Issue number12
StatePublished - Dec 2020
Externally publishedYes


  • CGRP (calcitonin gene-related peptide)
  • GERD (gastro-esophageal reflux disease)
  • ROS (reactive oxygen species)
  • inflammation
  • nociceptors

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology


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