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Bladder-colon chronic cross-sensitization involves neuro-glial pathways in male mice

Authors :
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
UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie
UCL - (MGD) Service de gastro-entérologie
Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN)
Université de Rouen Normandie (UNIROUEN)
Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB)
Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN)
Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Institute for Research and Innovation in Biomedicine (IRIB)
Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Normandie Université (NU)
CHU UCL Namur
Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen]
Hôpital Charles Nicolle [Rouen]
CHU Rouen
Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN)
Service d'urologie [Rouen]
Cancer and Brain Genomics (CBG)
Service Commun d'Analyse Comportementale (SCAC)
Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-High-tech Research Infrastructures for Life Sciences (HeRacLeS)
Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Service de nutrition [CHU Rouen]
Neuro-Dol (Neuro-Dol)
Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)
Source :
World journal of gastroenterology, Vol. 28, no.48, p. 6935-6949 (2022), World Journal of Gastroenterology, World Journal of Gastroenterology, 2022, 28 (48), pp.6935-6949. ⟨10.3748/wjg.v28.i48.6935⟩
Publication Year :
2022

Abstract

Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral hypersensitivity. Since pelvic organs share common sensory pathways, it is likely that those syndromes involve a cross-sensitization of the bladder and the colon. The precise pathophysiology remains poorly understood. To develop a model of chronic bladder-colon cross-sensitization and to investigate the mech-anisms involved. 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 distensions. Myeloperoxidase, used as a marker of colorectal inflammation, was measured in the colon, and colorectal permeability was measured using chambers. c-Fos protein expression, used as a marker of neuronal activation, was assessed in the spinal cord (L6-S1 level) using immunohistochemistry. Green fluorescent protein on the fractalkine receptor-positive mice were used to identify and count microglia cells in the L6-S1 dorsal horn of the spinal cord. The expression of NK1 receptors and MAPK-p38 were quantified in the spinal cord using western blot. Visceral hypersensitivity to colorectal distension was observed after the intravesical injection of acetic acid saline ( < 0.0001). This effect started 1 h post-injection and lasted up to 7 d post-injection. No increased permeability or inflammation was shown in the bladder or colon 7 d post-injection. Visceral hypersensitivity was associated with the increased expression of c-Fos protein in the spinal cord ( < 0.0001). In green fluorescent protein on the fractalkine receptor-positive mice, intravesical acetic acid injection resulted in an increased number of microglia cells in the L6-S1 dorsal horn of the spinal cord ( < 0.0001). NK1 receptor and MAPK-p38 levels were increased in the spinal cord up to 7 d after injection ( = 0.007 and 0.023 respectively). 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. We describe a new model of cross-organ visceral sensitization between the bladder and the colon in mice. Intravesical injections of acetic acid induced a long-lasting colorectal hypersensitivity to distension, mediated by neuroglial interactions, MAPK-p38 phosphorylation and the NK1 receptor.

Details

Language :
English
ISSN :
10079327
Database :
OpenAIRE
Journal :
World journal of gastroenterology, Vol. 28, no.48, p. 6935-6949 (2022), World Journal of Gastroenterology, World Journal of Gastroenterology, 2022, 28 (48), pp.6935-6949. ⟨10.3748/wjg.v28.i48.6935⟩
Accession number :
edsair.doi.dedup.....7449364d628fae35f85e0ff71461b3f8
Full Text :
https://doi.org/10.3748/wjg.v28.i48.6935⟩