title: The Nonsteroidal Anti-inflammatory Drug Diclofenac Reduces Acid-Induced Heartburn Symptoms in Healthy Volunteers.
abstract: OBJECTIVE
  We investigated the effects of diclofenac, a nonsteroidal anti-inflammatory drug that inhibits prostaglandin production, on induction of esophageal sensation by acid perfusion in healthy men.
  
  
  METHODS
  We performed a prospective, double-blind, placebo-controlled, 2-period, cross-over study over 3 visits in 12 healthy men. Diclofenac was given 6 hours and 2 hours before an acid perfusion test. During the test, hydrochloric acid (0.15 mol/L) was perfused into the lower esophagus for 30 minutes; we evaluated upper gastrointestinal symptoms using a validated categoric rating scale. Then, we calculated and assessed the acid perfusion sensitivity score (APSS). Biopsy specimens were collected by endoscopy of the distal esophagus before and after acid perfusion; levels of prostaglandin E2 (PGE2) (pg/mg) were measured in the samples using an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Compared with placebo, diclofenac significantly reduced the APSS for heartburn (82.2 ± 12.2 for placebo and 47.5 ± 8.9 for diclofenac; P < .01). Of the upper gastrointestinal symptoms, only the APSS for heartburn was reduced significantly by diclofenac. Compared with placebo, diclofenac reduced the overproduction of PGE2 by esophageal tissues after acid perfusion (23.3 ± 5.2 for placebo and 11.4 ± 3.5 for diclofenac; P < .05). APSS correlated with the development of heartburn and esophageal levels of PGE2 (r = 0.53; P < .05 for heartburn vs PGE2).
  
  
  CONCLUSIONS
  Diclofenac attenuated acid-induced heartburn by inhibiting PGE2 overproduction in the esophagus. Esophageal PGE2 might be involved in producing heartburn symptoms. Clinical Trials Registry no: UMIN000014595.
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors: Takashi
authors: T
authors: Kondo
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors: Tadayuki
authors: T
authors: Oshima
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors: Toshihiko
authors: T
authors: Tomita
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors: Hirokazu
authors: H
authors: Fukui
authors: Minase Research Institute, Pharmacological Research Laboratories, Ono Pharmaceutical Co, Ltd, Osaka, Japan.
authors: Hiroki
authors: H
authors: Okada
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors: Jiro
authors: J
authors: Watari
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan. Electronic address: miwahgi@hyo-med.ac.jp.
authors: Hiroto
authors: H
authors: Miwa
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004008:Diclofenac / Q000008:administration & dosage*; D015232:Dinoprostone / Q000032:analysis; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D004945:Esophagoscopy; D004947:Esophagus / Q000473:pathology; D064368:Healthy Volunteers; D006356:Heartburn / Q000517:prevention & control*; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010919:Placebos; D004008:Diclofenac; D015232:Dinoprostone
keywords: GERD; NERD; NSAID; Reflux; Treatment