ESOPHAGUS: Edited by Stuart J. SpechlerGastroesophageal reflux disease-related and functional heartburn pathophysiology and treatmentMiwa, Hiroto; Kondo, Takashi; Oshima, TadayukiAuthor Information Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan Correspondence to Hiroto Miwa, MD, PhD, Department of Internal Medicine, Division of Gastroenterology, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya City, Hyogo 663-8501, Japan. Tel: +81 798 45 6665; fax: +81 798 45 6665; e-mail: [email protected] Current Opinion in Gastroenterology: July 2016 - Volume 32 - Issue 4 - p 344-352 doi: 10.1097/MOG.0000000000000282 Buy Metrics Abstract Purpose of review 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. Recent findings 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. Summary 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. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.