We previously demonstrated reliable bladder contractions in neurologically-intact rats in response to proximal urethra electrical stimulation (PUES). We sought to investigate whether stimulating with a novel flexible electrode support, placed in an anatomically-similar position to that of a urethral sling, could improve bladder function in the setting of underactive bladder (UAB) caused by unilateral pelvic nerve transection (PNx).

The current study was approved by our Institutional Animal Care and Use Committee. Twenty-five urethane-anesthetized female Sprague-Dawley rats received ureteral diversion and transvesical catheters via laparotomy. The ventral pubis was removed to expose the urethra. A 3mm lattice with integrated bipolar electrodes (flexible electrode support) was placed between the urethra and vagina. Following 3 hours of continuous cystometry, 3 single-fill cystometrograms were performed prior to right PNx (eight of twenty-five rats served as sham PNx controls). After 1 hour of continuous cystometry, 3 single-fill cystometrograms were performed again. In PNx rats, the bladder was filled to the largest pre-PNx total bladder capacity (TBC) or 75% of lowest post-PNx TBC (the lower of the two volumes was tested first) and PUES was performed at 20, 30, 40, and 50 Hz (varied randomly) at 50 V for 60 sec stimulation/120 sec recovery periods. PUES was then repeated at the higher of the two test volumes. When voiding occurred, the bladders were emptied to calculate voiding efficiency (VE) and refilled to the test volumes. Measurements included TBC and VE before and after PNx, as well as, the presence or absence of bladder contraction or voiding during PUES. Data were analyzed using non-parametric repeated measures 2-Way ANOVA for sham PNx vs PNx comparisons of TBC and VE, and contingency analysis (CA) for comparisons of different test fill volumes and sequence/frequency effects of PUES.

After unilateral PNx, mean TBC increased by 80% and mean VE decreased by 71% (P <0.0001 for both); no changes were observed in sham PNx rats. PUES elicited voids (in absence of somatomotor response) at both test volumes; CA revealed significant stimulus frequency effect (P=0.0009) with lower frequencies more effectively evoking voiding contractions (percentage voiding 52, 23, 10, 10% at 20, 30, 40, 50 Hz, respectively, P=0.0013). Mean VE of voiding contractions was 115% of pre-PNx.

Pelvic surgery is a known etiology for UAB presumed to involve unilateral pelvic nerve plexus injury. We noted a significant increase in TBC and a decrease in VE after unilateral PNx that was not demonstrated in sham-PNx rats, thereby eliminating the possibility that our results were due to the cystometric fill-rate acclamation. Our flexible electrode support reversed sensory (TBC) and motor (VE) deficits that were caused by PNx.

Our validated unilateral PNx model induces conditions of dramatically increased TBC and decreased VE which effectively proxy for UAB. Following PNx, PUES with flexible electrode support at 20-30Hz elicited voiding contractions at decreased fill volumes with a reversal of VE changes, thereby normalizing functional voiding in this UAB model.