Introduction

Kilohertz frequency alternating current (KHFAC) neuromodulation of peripheral nerves is hypothesized to induce rapid and reversible nerve conduction block (1). Applied to the pudendal nerve, it could relax the pelvic musculature (2, 3). This might aid the emptying of the bladder and bowel providing a new therapy for urinary retention and dysfunctional defecation. The aims of the present study were: 1) to determine which stimulation parameters influence the effectiveness and safety of KHFAC neuromodulation and 2) to establish whether KHFAC neuromodulation of the pudendal nerves can relax the pelvic musculature.

Methods/Materials

In silico, we used the McIntyre-Richardson-Grill model to test which stimulation parameters improve the effectiveness of the nerve block (block threshold) and its safety (block threshold charge per phase). In vivo, the pudendal nerves were stimulated with 3 kHz to 40 kHz with an electrode-array in 14 urethane anesthetized male and female Sprague Dawley rats. Proximally, low frequency stimulation was applied (square wave, 20 Hz, 3 V, 20% duty cycle). Anal pressure, an indirect measure of pelvic muscle tone, was measured with a balloon catheter.

Results

The simulation model showed that block threshold and block threshold charge per phase are dependent on waveform (a square wave had the lowest block threshold), interphase delay, electrode-to-axon distance, interpolar distance, and electrode-array orientation. When introducing interphase delays, the required charge per phase can be reduced without increasing the amplitude.

The average anal pressure during unilateral high-frequency stimulation was significantly lower than the average peak anal pressure during low-frequency stimulation (p<0.001, n=167 stimulations of 18 pudendal nerves at 3 - 40 kHz, Figure 1a). Similar results were obtained with bilateral high-frequency stimulation (Figure 1b). Twenty and 40 kHz (square wave, amplitude of 10 V, 50% duty cycle) induced the largest relative anal pressure decrease (p>0.05).

Discussion

The simulations showed that a square wave has the lowest block threshold. This is an important consideration with regard to battery longevity. Furthermore, the addition of interphase delay in the electrical stimulation can improve its safety. In vivo, we showed in male and female rats that KHFAC neuromodulation of the pudendal nerve in the range of 3 – 40 kHz with a commercially available electrode-array can effectively decrease anal pressure.

Conclusions

Stimulation parameters and electorde design affect the efficacy and safety of KHFAC neuromodulation. In the future, KHFAC neuromodulation of the pudendal nerves might provide a new therapy for urinary retention and dysfunctional defecation that are refractory to conservative treatment options.

References

1. Kilgore KL, Bhadra N. Nerve conduction block utilising high-frequency alternating current. Med Biol Eng Comput. May 2004;42(3):394-406.

2. Bhadra N, Bhadra N, Kilgore K, Gustafson KJ. High frequency electrical conduction block of the pudendal nerve. J Neural Eng. Jun 2006;3(2):180-7.

3. Cai H, Morgan T, Pace N, Shen B, Wang J, Roppolo JR, et al. Low pressure voiding induced by a novel implantable pudendal nerve stimulator. Neurourol Urodyn. Apr 4 2019.