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1 Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2 Department of Surgery, Division of Urology, Duke University Medical Center and Durham VAMC, Durham, NC, USA
* To whom correspondence should be addressed. E-mail: pezzone{at}pitt.edu.
Chronic pelvic pain (CPP) disorders frequently overlap. We have demonstrated that acute and chronic colonic irritation can lead to neurogenic cystitis. We hypothesize that acute colonic irritation can sensitize urinary bladder afferents to mechanical and chemical stimuli. Single unit afferent activity was recorded from fine filaments of the pelvic nerve in urethane-anesthetized SD female rats before and 1 hour after intra-colonic administration of trinitrobenzenesulfonic acid (TNBS). Only spontaneously active afferents with receptive fields in the bladder and conduction velocities <2.5 m/s (unmyelinated C-fibers) were studied. Mechanical sensitivity was tested by bladder distension (BD) during saline infusion, while chemical sensitivity was tested with intra-vesical capsaicin, bradykinin, or Substance P. Colonic irritation increased the resting firing rate of bladder afferents two-fold (1.0 ± 0.2 vs 0.49 ± 0.2 imp/sec, p<0.05). Moreover, at low-pressure BDs (10-20 mm Hg), a greater percentage of afferents exhibited increased activity following TNBS (73% vs 27%, p<0.05). Although the magnitude of the afferent response to BD was unchanged at low pressures, the response was greatly enhanced at pressures 30 mm Hg and above (2.36 ± 0.56 vs. 8.55 ± 0.73 imp/sec, p<0.05). Responses to capsaicin, bradykinin, and Substance P were also significantly enhanced following TNBS, and all responses were blocked by bladder denervation. In rats, colonic irritation sensitizes urinary bladder afferents to noxious mechanical and chemical stimuli. Interruption of the neural input to the bladder minimized this effect, suggesting a local afferent pathway from the colon. Thus, the overlap of CPP disorders may be a consequence pelvic afferent cross-sensitization.
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