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

backgroundIrritable 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.

aimTo develop a model of chronic bladder-colon cross-sensitization and to investigate the mech-anisms involved.

methodsChronic 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.

resultsVisceral hypersensitivity to colorectal distension was observed after the intravesical injection of acetic acid

conclusionWe 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.