Neuromodulation Improves Stress Urinary Incontinence-Like Deficits in Female Rabbits

Abstract

Objective: Stress urinary incontinence (SUI) affects a third of the female population and is characterized by involuntary urine leakage during abdominal efforts such as sneezing, laughing, or coughing. Acute neuromodulation of the bulbospongiosus nerve (BsN) was shown to increase bladder efficiency in aged and multiparous rabbits. This study investigates the efficacy of sub-chronic BsN neuromodulation in alleviating SUI-like deficits in mature multiparous rabbits, characterized by increased urine leakage and reduced leak point pressure. Results: Using the voiding spot assay, we observed a 40% reduction in urine leakage events after 30 days of BsN stimulation, which correlated with a 60% increase in daily micturition volume, a 10-fold increase in voided volume, and improvements in voiding efficiency and leak point pressure compared to negative control animals. Conclusion: In multiparous rabbits, BsN neuromodulation improves important SUI-like metrics including bladder capacity and urethral closure, supporting the use of this bioelectronic modality as treatment for SUI.

Keywords: Bioelectronics; electrical stimulation; neural interfaces; pelvic floor disorders; pelvic innervation.

Figure 1.

wNClip implantation and function. (a), (b) Device schematic, and (c) picture of device on the BsN. (d) Schematic of the “slide-and-lock” mechanism of wNClip implantation. (e) Angular test for powering the wNClip using the external antenna. (f) Current output as a function of antenna distance and angle of 29 wNClip devices. Shaded green area shows targeted current output.

Figure 2.

BsN ES reduces leak frequency. (a) Representative image of leak event identified on the absorbent pad. MM-ES group (n = 8) showed a significant decrease in leak event frequency, (b) between baseline and treatment periods, and (c) from the negative control MM-sham group (n = 8).

Figure 3.

BsN ES achieved increased daily voided volume. MM-ES group showed increased (a and b) daily micturition; (c and d) increased average micturition per void. No significant differences were found between MM-ES and MM-sham groups for (e and f) voiding frequency; (g and h) daily water intake.

Figure 4.

BsN ES increases bladder capacity and urethral closure efficiency. Compared to MM-sham group, MM-ES group has increased (a) voided volume and (b) voiding efficiency, indicating the increased efficiency of BsM; increased (c) average storage P_ves, (d) maximum P_ves, and I leak point volume, indicating increased bladder capacity; and (f) increased leak point P_ves, which indicates increased urethral closure efficiency. All pressure values have been normalized against baseline and averaged for each animal. (YN: n = 5, MM-sham: n = 8, MM-ES: n = 8).

Figure 5.

BsM and bladder morphology after BsN ES. Representative images of masson trichrome-stained tissues of medial regions of (a–c) BsM, (e–g) whole bladder, (h–j) modified verhoeff's-stained magnified bladder wall cross-sections for YN, MM-sham, and MM-ES groups (top to bottom). Yellow triangles identify the urothelium layer in the magnified panels and double-ended black arrows demonstrate the detrusor muscle layer thickness in (h–j). Scale bars included. Analyses of (d) standardized medial BsM cross-sectional area, (k) standardized bladder weight, and (l) bladder detrusor muscle layer thickness as percentage of total bladder thickness, comparing YN, MM-ES and MM-sham groups.

Figure 6.

Research methods. (a) Experimental timeline. (b) Representative raw CMG graphs obtained during cytometry.