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Bladder-colon chronic cross-sensitization involves neuro-glial pathways in male mice
- 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.
- Subjects :
- Male
Inflammation
[SDV]Life Sciences [q-bio]
Urinary Bladder
Green Fluorescent Proteins
Gastroenterology
CX3C Chemokine Receptor 1
Pain
General Medicine
Rats
NK1 receptor
Rats, Sprague-Dawley
Mice, Inbred C57BL
Mice
Spinal Cord
Animals
Microglia
MAPK-p38
Colorectal Neoplasms
Proto-Oncogene Proteins c-fos
Cross-organ sensitization
Visceral hypersensitivity
Subjects
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⟩