Antinociceptive potency of enkephalins and enkephalinase inhibitors in the mouse model of colorectal distension-proof-of-concept.

Abstract

Irritable bowel syndrome (IBS) is a chronic disease characterized by abdominal pain and changes in bowel habits. Patients with IBS comprise a significant portion of attendants at the outpatient clinics. Targeting intestinal opioid receptors was found successful in alleviating pain and diarrhea-two major symptoms of IBS. In this study, we aimed to evaluate a novel potential pharmacological option: the use of enkephalinase inhibitors in therapy of visceral pain occurring in the course of IBS. We thus assessed the antinociceptive efficacy of enkephalins: Leu-enkephalin and Met-enkephalin, and enkephalinase inhibitors: opiorphin and sialorphin in the mouse model of visceral pain induced by colorectal distension. Leu-enkephalin, Met-enkephalin, and sialorphin, but not opiorphin, at the dose of 1 mg/kg injected subcutaneously potently decreased the visceromotor response to colon distension as compared to control. To conclude, enkephalinase inhibitors are worth being considered as potential therapeutics in patients with chronic abdominal pain and/or changed bowel habits, that is, suffering from IBS.

• Authors: Adam Fabisiak, Małgorzata Sobocińska, Elżbieta Kamysz, Jakub Fichna, Marta Zielińska
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 92 Issue 1 Pg. 1387-1392 (07 2018) ISSN: 1747-0285 [Electronic] England
• PMID: 29495100 (Publication Type: Letter, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 John Wiley & Sons A/S.

Chemical References

• Analgesics
• Enkephalins
• Neprilysin

Topics

• Amino Acid Sequence
• Analgesics (chemistry, therapeutic use)
• Animals
• Disease Models, Animal
• Enkephalins (chemistry, therapeutic use)
• Injections, Subcutaneous
• Irritable Bowel Syndrome (drug therapy, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Neprilysin (antagonists & inhibitors, metabolism)