title: Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical and chemical stimuli: an afferent origin of pelvic organ cross-sensitization.
abstract: 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 Sprague-Dawley female rats before and 1 h after intracolonic 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, whereas chemical sensitivity was tested with intravesical capsaicin, bradykinin, or substance P. Colonic irritation increased the resting firing rate of bladder afferents twofold (1.0 +/- 0.2 vs. 0.49 +/- 0.2 impulses/s, P < 0.05). Moreover, at low-pressure BDs (10-20 mmHg), 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 mmHg and above (2.36 +/- 0.56 vs. 8.55 +/- 0.73 impulses/s, 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 of pelvic afferent cross-sensitization.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Univ. of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Ustinova
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Fraser
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pezzone
mesh_terms: D000200:Action Potentials; D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D001696:Biomechanical Phenomena; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects; D003108:Colonic Diseases / Q000503:physiopathology*; D003714:Denervation; D005260:Female; D010388:Pelvis / Q000294:innervation*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology
chemical_list: D013373:Substance P; D014302:Trinitrobenzenesulfonic Acid; D002211:Capsaicin; D001920:Bradykinin