title: Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects.
abstract: OBJECTIVE
  Transient receptor potential vanilloid-1 (TRPV1) is a candidate for mediating acid-induced symptoms in the esophagus. We conducted studies to determine if the presence of acid in the mucosa/submucosa and direct activation of TRPV1 by capsaicin elicited symptoms in normal healthy subjects. We also studied the presence of TRPV1 receptors in the esophagus.
  
  
  METHODS
  Unsedated endoscopy was performed on healthy subjects with no symptoms. Using a sclerotherapy needle, normal saline (pH 2.0-7.5) was injected into the mucosa/submucosa, 5 cm above the Z line. In a separate group of healthy subjects, injection of capsaicin and vehicle was also studied. Quality of symptoms was reported using the McGill Pain Questionnaire, and symptom intensity using the visual analogue scale (VAS). Immunohistochemistry was performed on 8 surgical esophagus specimens using TRPV1 antibody.
  
  
  RESULTS
  Acid injection either did not elicit or elicited mild symptoms in subjects at all pH solutions. Capsaicin but not the vehicle elicited severe heartburn/chest pain in all subjects. Mean VAS for capsaicin was 91 ± 3 and symptoms lasted for 25 ± 1 minutes. Immunohistochemistry revealed a linear TRPV1 staining pattern between the epithelial layer and the submucosa that extended into the papillae. Eighty-five percent of papillae stained positive for TRPV1 with a mean 1.1 positive papillae per high-powered field.
  
  
  CONCLUSIONS
  The mechanism of acid-induced heartburn and chest pain is not the simple interaction of hydrogen ions with afferents located in the esophageal mucosa and submucosa. TRPV1 receptors are present in the lamina propria and their activation induces heartburn and chest pain.
authors.affiliation: Division of Gastroenterology, University of California Irvine, Irvine, CA, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology, University of California, San Diego, San Diego, CA, USA.|Gastroenterology Section, San Diego Veterans Administration Medical Center, La Jolla, CA, USA.
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Korsapati
authors.affiliation: Division of Gastroenterology, University of California, San Diego, San Diego, CA, USA.|Gastroenterology Section, San Diego Veterans Administration Medical Center, La Jolla, CA, USA.
authors.forename: Vikas
authors.initials: V
authors.lastname: Bhalla
authors.affiliation: Department of Pathology, University of California San Diego, San Diego, CA, USA.
authors.forename: Nissi
authors.initials: N
authors.lastname: Varki
authors.affiliation: Division of Gastroenterology, University of California, San Diego, San Diego, CA, USA.|Gastroenterology Section, San Diego Veterans Administration Medical Center, La Jolla, CA, USA.
authors.forename: Ravinder K
authors.initials: RK
authors.lastname: Mittal
keywords: Capsaicin; Chest pain; Esophagus; Heartburn; TRPV1 receptor