Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 309, Issue 6, Pages R629-R638Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00013.2015
Keywords
TRPV1; social stress; voiding frequency; cystometry
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Funding
- National Institutes of Health (NIH) [R37 DK053832, P01 HL095488, DK-051369, DK-065989, DK-060481]
- Foundation Leducq
- Totman Medical Research Trust
- Centers of Biomedical Research Excellence Program of the National Center [P20 RR-16435]
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Social stress has been implicated as a cause of urinary bladder hypertrophy and dysfunction in humans. Using a murine model of social stress, we and others have shown that social stress leads to bladder overactivity. Here, we show that social stress leads to bladder overactivity, increased bladder compliance, and increased afferent nerve activity. In the social stress paradigm, 6-wk-old male C57BL/6 mice were exposed for a total of 2 wk, via barrier cage, to a C57BL/6 retired breeder aggressor mouse. We performed conscious cystometry with and without intravesical infusion of the TRPV1 inhibitor capsazepine, and measured pressure-volume relationships and afferent nerve activity during bladder filling using an ex vivo bladder model. Stress leads to a decrease in intermicturition interval and void volume in vivo, which was restored by capsazepine. Ex vivo studies demonstrated that at low pressures, bladder compliance and afferent activity were elevated in stressed bladders compared with unstressed bladders. Capsazepine did not significantly change afferent activity in unstressed mice, but significantly decreased afferent activity at all pressures in stressed bladders. Immunohistochemistry revealed that TRPV1 colocalizes with CGRP to stain nerve fibers in unstressed bladders. Colocalization significantly increased along the same nerve fibers in the stressed bladders. Our results support the concept that social stress induces TRPV1-dependent afferent nerve activity, ultimately leading to the development of overactive bladder symptoms.
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