title: Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain.
abstract: BACKGROUND
  Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor 'transient receptor potential vanilloid 1'(TRPV1) are a potential drug class for GERD treatment.
  
  
  OBJECTIVE
  To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain.
  
  
  METHODS
  Twenty-two healthy men (20-31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli.
  
  
  METHODS
  intention-to-treat.
  
  
  RESULTS
  A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10-38%] and 28%, respectively (CI: 14-43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1-3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0-5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported 'feeling cold' and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4±0.3 °C and 0.7±0.3 °C, respectively, P<0.05).
  
  
  CONCLUSIONS
  AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD.
authors.affiliation: Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
authors.forename: A L
authors.initials: AL
authors.lastname: Krarup
authors.forename: L
authors.initials: L
authors.lastname: Ny
authors.forename: M
authors.initials: M
authors.lastname: Astrand
authors.forename: A
authors.initials: A
authors.lastname: Bajor
authors.forename: F
authors.initials: F
authors.lastname: Hvid-Jensen
authors.forename: M B
authors.initials: MB
authors.lastname: Hansen
authors.forename: M
authors.initials: M
authors.lastname: Simrén
authors.forename: P
authors.initials: P
authors.lastname: Funch-Jensen
authors.forename: A M
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D000700:Analgesics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004935:Esophageal Diseases / Q000139:chemically induced / Q000188:drug therapy*; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000700:Analgesics; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human