Electroacupuncture improves cyclophosphamide-induced bladder overactivity by reducing mechanotransduction in the rat urothelium.

Abstract

Objective: To investigate whether electroacupuncture (EA) therapy for overactive bladder (OAB) exerts its effect by modulating mechanosensitive channels in the urothelium, thereby improving bladder sensory function.

Methods: In this study, a rat model of OAB was created by using intraperitoneal injections of cyclophosphamide. We performed either EA or bladder perfusion with HC-067047 [a transient receptor potential vanilloid 4 (TRPV4) antagonist] and assessed the efficacy of electro-acupuncture in the treatment of OAB in rats viaurodynamic determination and Void spot assay. tissue morphology, distribution and expression of the TRPV4 protein and the amount of adenosine triphosphate (ATP) and Ca2+ released from urothelial cells in each group of rats were observed to identify the mechanism by which electroacupuncture improves OAB in rats.

Results: EA ameliorated bladder function and voiding behaviour, improved bladder uroepithelial tissue morphology, and significantly reduced the immun-ofluorescence intensity and the mRNA and protein expression levels of TRPV4 in the uroepithelium of OAB rats. Moreover, the simulated mechanical stimulation-induced increases in Ca²⁺ concentration and the release of ATP and acetylcholine (Ach) from bladder urothelial cells were inhibited. The changes in EA followed the same trend as those in HC-067047.

Conclusions: These results suggest that EA inhibits bladder sensory function by downregulating the expression of mechanically activated TRPV4 ion channels distributed in bladder urothelial cells, which correspondingly decreases the inward flow of extracellular Ca²⁺ and reduces the release of ATP and Ach, thereby attenuating excitatory signals.