493 DEVELOPMENT OF A NEUROGENIC BLADDER IN TRANSIENT RECEPTOR POTENTIAL VANILLOID 1 KNOCKOUT MICE

Abstract

INTRODUCTION AND OBJECTIVES: Bladder pain of unknown etiology has been associated with co-morbid conditions and functional abnormalities in adjacent pelvic organs. This phenomenon is called “crosssensitization” and occurs predominantly via convergent neural pathways connecting distinct pelvic organs. Our previous studies showed that colonic inflammation can cause detrusor instability via activation of transient receptor potential vanilloid 1 (TRPV1) signaling pathways. In this study, we aimed to determine whether cross-sensitization in the pelvis can develop in the absence of TRPV1 receptors and lead to a neurogenic bladder. METHODS: Four groups of adult male mice (N 25) were included in the study: 2 groups of C57BL/6 wild-type (WT) mice with and without acute colitis (induced by intracolonic trinitrobenzene sulfonic acid, TNBS) and 2 groups of TRPV1 knockout mice (TRPV1 / ) mice with and without acute colitis. Mice were sacrificed at day 3 after the induction of pelvic organ cross-sensitization by acute colitis and the function of the detrusor was evaluated in vitro using isolated detrusor smooth muscle (DSM) strips. The level of inflammation in the distal colon and urinary bladder was evaluated by the myeloperoxidase (MPO) assay. The contractility of DSM strips was studied in response to potassium chloride test, electric field stimulation and relaxation of DSM by Rho kinase inhibitor. RESULTS: In WT mice, acute colitis caused 2-fold up-regulation of MPO levels in the colon whereas in TRPV1 / mice an increase reached 1.5 fold (p 0.05 to respective control). MPO levels were unchanged in the bladders from both groups. The contractile response of DSM strips to electric stimulation was significantly increased after colitis in WT mice (85.97 12.27 g/g) when compared to control group (44.39 10.81 g/g, p 0.05). The same changes were observed in the TRPV1 / group with pelvic organ cross-sensitization. The use of Rho kinase inhibitor Y27632 induced DSM relaxation in WT group by 72.87 10.40% whereas it was only 39.38 6.46% in the TRPV / group (N 6, p 0.05 to WT). CONCLUSIONS: Our data provide evidence that the absence of TRPV1 receptors does not eliminate the occurence of cross-sensitization in the pelvis and TRPV / mice develop a neurogenic bladder. However, DSM from TRPV / mice showed decreased relaxation in response to a Rho kinase inhibitor suggesting alterations in DSM signaling pathways.