Although
gastroesophageal reflux disease (
GERD) is a common disorder in Western countries, with a significant impact on quality of life and healthcare costs, the mechanisms involved in the pathogenesis of symptoms remain to be fully elucidated.
GERD symptoms and complications may result from a multifactorial mechanism, in which
acid and
acid-
pepsin are the important noxious factors involved. Prolonged contact of the esophageal mucosa with the refluxed content, probably caused by a defective anti-reflux barrier and
luminal clearance mechanisms, would appear to be responsible for macroscopically detectable injury to the esophageal squamous epithelium. Receptors on
acid-sensitive nerve endings may play a role in nociception and esophageal sensitivity, as suggested in animal models of chronic
acid exposure. Meanwhile, specific
cytokine and
chemokine profiles would appear to underlie the various esophageal phenotypes of
GERD, explaining, in part, the genesis of
esophagitis in a subset of patients. Despite these findings, which show a significant production of inflammatory mediators and
neurotransmitters in the pathogenesis of
GERD, the relationship between the
hypersensitivity and esophageal
inflammation is not clear. Moreover, the large majority of
GERD patients (up to 70%) do not develop esophageal erosions, a variant of the condition called
non-erosive reflux disease. This summary aims to explore the inflammatory pathway involved in
GERD pathogenesis, to better understand the possible distinction between erosive and
non-erosive reflux disease patients and to provide new therapeutic approaches.