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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2013

Open Access 01-12-2013 | Research

Lack of transient receptor potential vanilloid 1 channel modulates the development of neurogenic bladder dysfunction induced by cross-sensitization in afferent pathways

Authors: Qi Lei, Xiao-Qing Pan, Antonio N Villamor, Tirsit S Asfaw, Shaohua Chang, Steven A Zderic, Anna P Malykhina

Published in: Journal of Neuroinflammation | Issue 1/2013

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Abstract

Background

Bladder pain of unknown etiology has been associated with co-morbid conditions and functional abnormalities in neighboring pelvic organs. Mechanisms underlying pain co-morbidities include cross-sensitization, which occurs predominantly via convergent neural pathways connecting distinct pelvic organs. Our previous results showed that colonic inflammation caused detrusor instability via activation of transient receptor potential vanilloid 1 (TRPV1) signaling pathways, therefore, we aimed to determine whether neurogenic bladder dysfunction can develop in the absence of TRPV1 receptors.

Methods

Adult male C57BL/6 wild-type (WT) and TRPV1−/− (knockout) mice were used in this study. Colonic inflammation was induced by intracolonic trinitrobenzene sulfonic acid (TNBS). The effects of transient colitis on abdominal sensitivity and function of the urinary bladder were evaluated by cystometry, contractility and relaxation of detrusor smooth muscle (DSM) in vitro to various stimuli, gene and protein expression of voltage-gated sodium channels in bladder sensory neurons, and pelvic responses to mechanical stimulation.

Results

Knockout of TRPV1 gene did not eliminate the development of cross-sensitization between the colon and urinary bladder. However, TRPV1−/− mice had prolonged intermicturition interval and increased number of non-voiding contractions at baseline followed by reduced urodynamic responses during active colitis. Contractility of DSM was up-regulated in response to KCl in TRPV1−/− mice with inflamed colon. Application of Rho-kinase inhibitor caused relaxation of DSM in WT but not in TRPV1−/− mice during colonic inflammation. TRPV1−/− mice demonstrated blunted effects of TNBS-induced colitis on expression and function of voltage-gated sodium channels in bladder sensory neurons, and delayed development of abdominal hypersensitivity upon colon-bladder cross-talk in genetically modified animals.

Conclusions

The lack of TRPV1 receptors does not eliminate the development of cross-sensitization in the pelvis. However, the function of the urinary bladder significantly differs between WT and TRPV−/− mice especially upon development of colon-bladder cross-sensitization induced by transient colitis. Our results suggest that TRPV1 pathways may participate in the development of chronic pelvic pain co-morbidities in humans.
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Metadata
Title
Lack of transient receptor potential vanilloid 1 channel modulates the development of neurogenic bladder dysfunction induced by cross-sensitization in afferent pathways
Authors
Qi Lei
Xiao-Qing Pan
Antonio N Villamor
Tirsit S Asfaw
Shaohua Chang
Steven A Zderic
Anna P Malykhina
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2013
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-10-3

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