Bladder mechanical compliance is unaffected by TRPV1 or TRPM8 channel agonism in female mice

Transient receptor potential ion channels (TRPs) are temperature and chemical sensors involved in nociception and may become sensitized during inflammation. TRP melastatin type 8 (TRPM8) is sensitive to cool temperatures (42°C) and activated by capsaicin. Both are distributed throughout multiple cell types the urinary bladder but their exact role in micturition remains unknown. Previously, we discovered that male mice had significantly more cells that expressed both Trpv1 and Pdgfrα (a fibroblast marker) mRNA than females. Also, in male mice menthol caused an increase in bladder compliance that was blocked by capsaicin, suggesting reciprocal regulation of channel function. Thus, this study sought to determine if bladder mechanical compliance following TRPV1 and TRPM8 agonism is altered in female mice. We hypothesize that TRPV1 and TRPM8 channel activation increases mechanical compliance in the urinary bladder of female mice. Bladders from female C57Bl/6 mice (ages 10-14 weeks) were cannulated on the Pentaplanar Reflected Image Macroscopy (PRIM) System to simultaneously record intravesical pressure, transient pressure events, geometry, and infused volume during ex vivo bladder filling. From these recordings, mechanical compliance was then calculated as the Cauchy stress and stretch. To determine the implications of activating one or both channels on bladder compliance, experiments were performed in the presence of the TRPV1 agonist capsaicin (200 nM), the TRPM8 agonist menthol (600 µM), or menthol and capsaicin together. The transient pressure events were smaller in female mice compared to males. Unlike male mice, neither capsaicin nor menthol altered bladder pressure, volume, or mechanical compliance. Sequential application of both agonists also had no effect. These findings suggest that TRPM8 is reciprocally regulated by TRPV1 agonism in male mice, but not female mice. Further, activation of TRPM8 alters the mechanical properties of the bladder through a mechanism specific to male mice. Additional studies will determine the cellular location of TRPV1 and TRPM8 in the bladder wall and possible mechanisms by which these channels can reversibly alter bladder compliance. Funded by NIH R01-DK135696. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.