Article Text

PDF
Original article
Histamine H4 and H1 receptors contribute to postinflammatory visceral hypersensitivity
  1. Annemie Deiteren1,
  2. Joris G De Man1,
  3. Nathalie E Ruyssers1,
  4. Tom G Moreels1,2,
  5. Paul A Pelckmans1,2,
  6. Benedicte Y De Winter1
  1. 1Division of Gastroenterology, Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium
  2. 2Department of Gastroenterology, Antwerp University Hospital, Antwerp, Belgium
  1. Correspondence to Professor Benedicte De Winter, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Antwerp B-2610, Belgium; benedicte.dewinter{at}uantwerpen.be

Abstract

Objectives Substantial evidence implicates mast cells and their main constituent histamine in the pathogenesis of visceral hypersensitivity. We explored the specific contribution of histamine H4 (H4R) and H1 (H1R) receptors to visceral hypersensitivity in a postinflammatory rat model.

Design Trinitrobenzenesulfonic acid (TNBS)-colitis was monitored individually by colonoscopy: first on day 3 to confirm the presence of colitis and then every 4 days, starting from day 10, to monitor convalescence and determine the exact timepoint of endoscopic healing in each rat. Experiments were performed 3 days after endoscopic resolution of colitis. Visceral sensitivity was assessed by quantifying visceromotor responses (VMRs) to colorectal distension. Colonic mast cell numbers, histamine release and H4R and H1R mRNA expression were quantified. JNJ7777120 (H4R antagonist) and/or levocetirizine (H1R antagonist) were administered 30 min prior to VMR assessment or histamine release assay.

Results Postcolitis rats displayed a higher number of colonic mast cells, excessive histamine release and significantly enhanced VMRs. Heightened VMRs were dose-dependently reduced by JNJ7777120 and levocetirizine; combined administration of JNJ7777120 and levocetirizine potentiated the antinociceptive effect. In the colon, both H4R and H1R mRNA were present; in the dorsal root ganglia, only H1R mRNA was found. Only colonic H4R mRNA expression was increased in postcolitis rats. Excessive histamine release in postcolitis rats was attenuated by the highest dose of JNJ7777120.

Conclusions H4R and H1R antagonists dose-dependently reduce and even normalise postinflammatory visceral hypersensitivity via different underlying mechanisms but with a synergistic effect. Both receptor subtypes represent promising targets for the treatment of postinflammatory visceral hypersensitivity.

  • VISCERAL HYPERSENSITIVITY
  • MAST CELLS
  • HISTAMINE
  • VISCERAL NOCICEPTION

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles