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Sensitization of Pelvic Nerve Afferents and Mast Cell Infiltration in the Urinary Bladder Following Chronic Colonic Irritation is Mediated by Neuropeptides

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By EE Ustinova • www.ProHealth.com • November 8, 2006


Journal: American Journal of Physiology. Renal Physiology. 2006 Aug 22; [E-publication ahead of print] Authors and affiliation: Ustinova EE, Gutkin DW, Pezzone MA. Division of Gastroenterology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States. PMID: 16926445

Irritable bowel syndrome and interstitial cystitis frequently overlap. We've shown that acute colitis sensitizes urinary bladder afferents to both mechanical and chemical stimuli and that chronic colitis likewise produces neurogenic cystitis. We hypothesize that chronic irritation of the colon releases neuropeptides from bladder afferents leading to receptor sensitization and neurogenic inflammation.

Female Sprague-Dawley rats received intrarectal trinitrobenzenesulfonic acid (TNBS) or vehicle 3 days following either systemic capsaicin (CP) pretreatment or vehicle. Ten days later, action potentials of single unit pelvic C-fiber afferents with receptive fields in the bladder were recorded under urethane anesthesia during graded bladder distensions (UBD) or intravesical capsaicin (vCP) administration. In controls, UBD increased bladder afferent firing in proportion to intravesical pressure. At intravesical pressures of 30 mm Hg and above, the percent increase in afferent firing was significantly accentuated following TNBS as compared to controls (1222 +/-176% vs. 624 +/-54%, p<0.01). The response to vCP was also enhanced (4126 +/-775% vs. 1979 +/- 438%, p<0.01). Systemic depletion of neuropeptides from sensory nerves abolished these effects. Histological examination of the bladders revealed an increase in mast cell density in TNBS-treated animals as compared to controls (18.02 +/-1.25 vs. 3.11 +/-0.27 mast cells per 100x field, p<0.01). This effect was significantly ameliorated with CP (10.25 +/-0.95, p<0.5 vs TNBS-treated animals).

In summary, chronic colonic irritation in the rat sensitizes urinary bladder afferents to noxious stimuli and causes mast cell infiltration in the bladder. Depletion of neuropeptides from sensory afferents diminishes these effects suggesting they play an important role.

Keywords: afferent, sensitization, bladder, colitis.




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