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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Bladder-colon chronic cross-sensitization involves neuro-glial pathways in male mice
Karim Atmani, Fabien Wuestenberghs, Maximilien Baron, Illona Bouleté, Charlène Guérin, Wafa Bahlouli, David Vaudry, Jean Claude do Rego, Jean-Nicolas Cornu, Anne-Marie Leroi, Moïse Coëffier, Mathieu Meleine, Guillaume Gourcerol
Karim Atmani, Fabien Wuestenberghs, Maximilien Baron, Illona Bouleté, Charlène Guérin, Wafa Bahlouli, David Vaudry, Jean-Nicolas Cornu, Anne-Marie Leroi, Moïse Coëffier, Mathieu Meleine, Guillaume Gourcerol, Nutrition, Gut and Brain Unit (Inserm U1073), Institute for Research and Innovation in Biomedicine, Université de Rouen Normandie, Rouen 76000, France
Fabien Wuestenberghs, Department of Gastroenterology and Hepatology, Université Catholique de Louvain, CHU UCL Namur, Yvoir 5530, Belgium
Fabien Wuestenberghs, Anne-Marie Leroi, Guillaume Gourcerol, Department of Physiology, CHU Rouen, Université de Rouen Normandie, Rouen 76031, France
Maximilien Baron, Jean-Nicolas Cornu, Department of Urology, CHU Rouen, Université de Rouen Normandie, Rouen 76000, France
David Vaudry, Inserm, UMR 1245, Team Epigenetics and Pathophysiology of Neuro-developmental Disorders, Université de Rouen Normandie, Rouen 76000, France
Jean Claude do Rego, Behavioural Analysis Platform (SCAC), HeRacLeS Inserm US51-CNRS UAR2026, Institute for Research and Innovation in Biomedicine, Université de Rouen Normandie, Rouen 76000, France
Moïse Coëffier, Department of Nutrition, CHU Rouen, Université de Rouen Normandie, Rouen 76000, France
Mathieu Meleine, Inserm U1107, NeuroDol, Clermont Auvergne University, Clermont-Ferrand 63000, France
Author contributions: Gourcerol G and Leroi AM designed the research study; Atmani K, Meleine Mathieu, Baron M, Bouleté I, Guérin C, Vaudry D, do Rego JC and Bahlouli W performed the research; Atmani K, Wuestenberghs F, Meleine M and Gourcerol G analyzed the data; Atmani K, Wuestenberghs F and Gourcerol G drafted the manuscript; Atmani K, Wuestenberghs F, Baron M, Bouleté I, Guérin C, Bahlouli W, Vaudry D, do Rego JC, Cornu JN, Leroi AM, Coëffier M, Meleine M and Gourcerol G critically reviewed the manuscript for important intellectual content; All authors approved the final version of the article, including the authorship list; Gourcerol G accepts official responsibility for the overall integrity of the manuscript.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals, and the protocol was approved by the local Ethics Committee for Animal Experiments (CENOMEXA No: N/02-01-13/02/01-16).
Conflict-of-interest statement: None of the authors have any conflicts of interest.
Data sharing statement: No additional data is available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Guillaume Gourcerol, MD, PhD, Chief Doctor, Professor, Department of Physiology, CHU Rouen, Université de Rouen Normandie, 1 Rue de Germont, Rouen 76031, France. guillaume.gourcerol@chu-rouen.fr
Received: May 18, 2022
Peer-review started: May 18, 2022
First decision: August 1, 2022
Revised: October 2, 2022
Accepted: October 26, 2022
Article in press: October 26, 2022
Published online: December 28, 2022
ARTICLE HIGHLIGHTS
Research background
Limited mechanistic data is available in the context of overlap between bladder pain syndrome and irritable bowel syndrome. Based on the fact that pelvic organs share common sensory pathways, a few studies have offered evidence that cross-sensitization between the bladder and the colon may explain sensitization of both organs. This may involve primary extrinsic afferents or central sensitization, both at the spinal and supraspinal levels.
Research motivation
The precise pathophysiology involved in cross-sensitization of the bladder and the colon remains poorly understood.
Research objectives
The objectives of this study were to develop a model of chronic bladder-colon cross-sensitization and to investigate the mechanisms involved.
Research methods
Chronic cross-organ visceral sensitization was obtained in C57BL/6 mice using ultrasound-guided intravesical injections of acetic acid under brief isoflurane anesthesia. Colorectal sensitivity was assessed in conscious mice by measuring intracolonic pressure during isobaric colorectal distension. Three different inhibitors/antagonists were assessed to gain a better understanding of which pathway could be involved in the cross-sensitization process.
Research results
Visceral hypersensitivity to colorectal distension was observed after the intravesical injection of acetic acid. This effect started 1 h post-injection and lasted up to 7 d post-injection. Colorectal sensitization was prevented by intrathecal or intracerebroventricular injections of minocycline, a microglia inhibitor, by intracerebroventricular injection of CP-99994 dihydrochloride, a NK1 antagonist, and by intracerebroventricular injection of SB203580, a MAPK-p38 inhibitor.
Research conclusions
We described a new model of cross-organ visceral sensitization between the bladder and the colon in mice lasting up to 7 d. Intravesical injections of acetic acid induced colorectal hypersensitivity to distension, mediated by neuroglial interactions, MAPK-p38 phosphorylation and the NK1 receptor.
Research perspectives
A bladder-colon chronic cross-sensitization mouse model using intravesical injections of acetic acid can be used as a preclinical model of overlap between bladder pain syndrome and irritable bowel syndrome.
