Efficacy of KPR‐5714, a selective transient receptor potential melastatin 8 antagonist, on chronic psychological stress‐induced bladder overactivity in male rats

Abstract

AbstractAimsChronic psychological stress aggravates lower urinary tract symptoms. Among others, water avoidance stress is a chronic psychological stressor that plays a causal role in the exacerbation and development of bladder dysfunction in rats. In this report, the effects of KPR‐5714, which is a selective transient receptor potential melastatin 8 (TRPM8) antagonist, on bladder overactivity induced by water avoidance stress were examined.MethodsMale rats were subjected to water avoidance stress for 2 h per day for 10 consecutive days. The effects of water avoidance stress on voiding behavior using metabolic cages and histological bladder changes were investigated in rats. The involvement of bladder C‐fiber afferent on voiding frequency in rats exposed to water avoidance stress was assessed using capsaicin. The effects of KPR‐5714 on storage dysfunction in rats subjected to water avoidance stress were examined.ResultsIn voiding behavior measurements, water avoidance stress‐induced storage dysfunction, causing a decrease in the mean voided volume and increasing voiding frequency. A comparison of bladders from normal rats and rats exposed to water avoidance stress showed no histological differences. Water avoidance stress‐induced bladder overactivity was completely inhibited by pretreatment with capsaicin. KPR‐5714 showed a tendency to increase the mean voided volume and significantly decreased the voiding frequency without affecting the total voided volume in these rats.ConclusionThe results suggest that KPR‐5714 is a promising option for treating chronic psychological stress‐induced bladder overactivity.