title: Gastroesophageal reflux disease-related and functional heartburn: pathophysiology and treatment.
abstract: Patients who continue to experience heartburn symptoms despite adequate-dose proton pump inhibitor therapy have unmet clinical needs. In this review, we focus on the most recent findings related to the mechanism of heartburn symptom generation, and on the treatment of gastroesophageal reflux disease-related and functional heartburn.
  
  
  
  The immunological mechanism in the esophageal mucosa has been addressed as a potential mechanism of the onset of esophageal mucosa damage and the generation of heartburn symptoms. Peripheral or central hypersensitivity in viscera is a potentially unifying pathophysiological concept in functional heartburn. Vonoprazan, a novel and potent first-in-class potassium-competitive acid blocker, is expected to prove useful in the treatment of reflux disease.
  
  
  
  New findings in the mechanisms of heartburn symptom generation are emerging, including the immunological mediation of esophageal mucosal damage and the development of visceral hypersensitivity in functional heartburn. In the future, we anticipate the emergence of new and specific therapeutic options based on these mechanisms, with less dependence on acid-suppressing agents.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Oshima
mesh_terms: D050782:Esophageal pH Monitoring / Q000379:methods; D004947:Esophagus / Q000503:physiopathology*; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000503:physiopathology*; D006356:Heartburn / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D009092:Mucous Membrane / Q000473:pathology*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C552956:1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; D054328:Proton Pump Inhibitors; D011758:Pyrroles; D013449:Sulfonamides