Long-Term Visceral Hypersensitivity Following Induction of Chemical Colitis is Primarily Reduced via Kappa Opiate Pathways - A Comparative Study of Different Opioidergic Subtypes

Abstract

Author Affiliations 1Department of Visceral Surgery and Medicine, Inselspital, Switzerland 2Department of Clinical Research, Inselspital, Switzerland Received: September 25, 2020 | Published: October 02, 2020 Corresponding author: Juergen MGschossmann, Klinikum Forchheim, Department of Internal Medicine, Krankenhausstrasse 10, D-91301 Forchheim, Germany DOI: 10.26717/BJSTR.2020.30.005024 Background/Aims: Transient gastrointestinal infections frequently precede functional bowel disorders with altered visceral sensory function. The aim of our study was a) to demonstrate the long-term effect of a chemically induced colitis on visceral sensory function in response to phasic colorectal distensions (CRD) and b) to analyze the impact of different opiate receptor agonists (ORA) and the NMDA antagonist ketamine on modulation of visceral hypersensitivity following chemical colitis in a rat model. Methods: In forty male Lewis rats, 6 weeks after induction of trinitrobenzene sulfonic acid (TNB) colitis (colitis group) versus saline (control group), electromyographic recordings of CRD were performed. Different ORA and/or ketamine were administered intraperitoneally. Results: The chemically induced colitis was followed by persistent visceral hypersensitivity. TNB-treated animals showed a significant increase of the visceromotor response (VMR) (p=0.006). While κ-ORA U50.488 had the strongest effect on VMR (p Conclusions: In our visceral hypersensitivity model in rats and at the applied doses, the typical side effects of the μ-ORA fentanyl and morphine could be avoided by use of κ-ORA without any loss of analgesic effect on visceral nociception. Keywords: Chemical Colitis; Functional Bowel Disorders; Opiates, Rat Model; Visceral Nociception