Introduction

Incomplete bladder emptying due to detrusor underactivity (DU) is a significant urological problem underlying underactive bladder (UAB). Also, TRPV4 has been reported to be one of the mechanosensitive channels expressed in the bladder. In this study, we sought to produce a consistent rat model of UAB with the modification of our previous model of pelvic nerve crush (PNC) (2016 AUA) and evaluated the therapeutic effect of intravesical application of a TRPV4 agonist on the UAB condition.

Methods

In female Sprague-Dawley rats, the visceral branches of bilateral pelvic nerves were identified near the internal iliac vessels and bilateral PNC was made by two times of nerve compression of either side with each 20-seconds duration using sharp forceps. After 10 days, awake cystometrograms (CMG) were recorded in sham control and PNC rats. Then, in both groups, a TRPV4 agonist (GSK1016790A) was continuously administered into the bladder and the CMG parameters were compared before and after intravesical drug administration.

Results

The bladder weight was significantly increased in PNC rats vs. control rats. In CMG, PNC rats showed significant increases in voided volume, post-void residual urine volume, and residual urine rate compared to control rats. PNC rats also revealed the significant increases in intercontraction intervals (ICI), a number of non-voiding contractions, and threshold pressure while the amplitude during voiding was significantly decreased (table). In the TRPV4 administration study, intravesical application of 1.5µM of GSK 1016790A significantly decreased ICI, voided volume, and post-void residual urine volume in PNC rats while it did not significantly affect any CMG parameters in control rats._x000D_ _x000D_

Conclusions

Rats with pelvic nerve injury induced by the modified PNC method, which showed the characteristics of DU, seem to be an appropriate model for evaluation of peripheral neurogenic mechanisms of UAB. Also TRPV4 that reduced the bladder capacity and residual urine volume could be a potential target for the treatment of UAB.

Funding

none