title: The pathogenesis of heartburn in nonerosive reflux disease: a unifying hypothesis.
abstract: Heartburn is a symptom complex that has traditionally been accepted as an acid-mediated event and a reliable indicator of gastroesophageal reflux disease. Recently, however, these concepts have been questioned because patients with endoscopy-negative "heartburn" have lower response rates to acid suppression with proton pump inhibitors than do patients with endoscopy-positive "heartburn," ie, erosive esophagitis. As explanation for this, 3 different mechanisms have been proposed to explain the occurrence of heartburn in the endoscopy-negative setting. They are: esophageal visceral hypersensitivity, sustained esophageal contractions, and abnormal tissue resistance. In this report, we review the observations in support of each concept and propose a means for reconciling them under one hypothesis: abnormal tissue resistance. Essential to this review and to the conclusions drawn about the pathogenesis of heartburn in nonerosive reflux disease is a reaffirmation of the definition of reflux-associated "heartburn" as an acid-mediated event requiring "relief by antacids" as a necessary component of the history.
authors.affiliation: Tulane University Health Sciences Center, Department of Medicine SL-35, 1430 Tulane Avenue, New Orleans, Louisiana 70112, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Barlow
authors.forename: Roy C
authors.initials: RC
authors.lastname: Orlando
mesh_terms: D016145:Endoscopy, Digestive System; D004848:Epithelium / Q000378:metabolism; D004935:Esophageal Diseases / Q000150:complications; D004947:Esophagus / Q000378:metabolism / Q000503:physiopathology; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006356:Heartburn / Q000209:etiology*; D006801:Humans; D008954:Models, Biological; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology; D010539:Permeability; D012678:Sensation Disorders / Q000150:complications