title: Social stress in mice induces urinary bladder overactivity and increases TRPV1 channel-dependent afferent nerve activity.
abstract: 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.
authors.affiliation: Department of Surgery (Urology), University of Vermont College of Medicine, Vermont Children's Hospital, Burlington, Vermont; Gerald.Mingin@uvm.edu.
authors.forename: Gerald C
authors.initials: GC
authors.lastname: Mingin
authors.affiliation: Department of Pharmacology, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Heppner
authors.affiliation: Department of Pharmacology, University of Vermont College of Medicine, Burlington, Vermont;
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Tykocki
authors.affiliation: Department of Surgery (Urology), University of Vermont College of Medicine, Vermont Children's Hospital, Burlington, Vermont;
authors.forename: Cuixia Shi
authors.initials: CS
authors.lastname: Erickson
authors.affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont; and.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Vizzard
authors.affiliation: Department of Pharmacology, University of Vermont College of Medicine, Burlington, Vermont; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
mesh_terms: D000374:Aggression / Q000502:physiology / Q000523:psychology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000378:metabolism*; D012931:Social Environment; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014521:Urethra / Q000473:pathology; D001743:Urinary Bladder / Q000473:pathology; D053201:Urinary Bladder, Overactive / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D014554:Urination
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin
keywords: TRPV1; cystometry; social stress; voiding frequency