62 A Novel Non-Invasive Method to Monitor Gastric Motility in Mice: Role of CRF During Cold Stress

by irritative micturition patterns and increased sensitivity of bladder afferents.A role of capsaicin-sensitive afferents was clearly demonstrated, as capsaicin pretreatment prevented the development of cross-sensitization and the associated bladder mastocytosis.Furthermore, acute bladder afferent sensitization was noted at 1 hr, while sub-acutely, the degree of bladder mast cell migration was directly and temporally associated with increases in bladder permeability and decreases in bladder voiding intervals (irritative voiding).A causal role of mast cells could not be established.We hypothesize that pelvic organ mast cell infiltration, mediator release, and consequential afferent modulation are the primary mechanisms responsible for chronic pelvic organ sensitization.Methods: Intra-colonic TNBS (or vehicle) was administered to mast cell deficient mice (W/Wv) and wild type (WT) littermates.Eight days later, colonic and bladder mast cells were quantified, and under urethane anesthesia, bladder voiding intervals and permeability were measured using saline cystometry and fluorescein, respectively.Animal weights were recorded daily throughout the experiment.Results: Animal weights were decreased following intra-colonic TNBS beginning as early as day 2 and peaking at 15-20% on day 4 (p<0.05).By day 6, weights had normalized and were no different from untreated controls.Histologic colitis paralleled decreases in weight and was no different in the c-kit deficient mice as compared to WT whose mast cell counts were elevated three-fold (p<0.05).Colonic mast cell counts in W/Wv mice were significantly less at baseline compared to WT mice, and there was no change following TNBS.In the bladder, mast cell responses paralleled those of the colon despite the lack of any acute inflammatory changes.Voiding intervals were decreased by 33% in TNBS-treated WT mice (p<0.05)(irritative voiding) but were unchanged in W/Wv mice.Likewise, bladder permeability was increased 4-fold (p<0.05) in TNBS-treated WT mice but unchanged in W/Wv mice.Conclusion: Mast cells and afferent nerves both play important roles in the development and maintenance of pelvic organ sensitization.Although afferent nerves and neuropeptide release are likely response for the acute effects, it would appear that the mast cells and their effects play an important role in maintaining pelvic organ sensitization.