Suppression of Urinary Voiding “on Demand” by High-Frequency Stimulation of the S1 Sacral Nerve Root in Anesthetized Rats

Abstract

Objectives: High-frequency (kHz) stimulation of preganglionic pelvic nerve afferents can inhibit voiding in both anesthetized and conscious rats. The afferents travel via the S1 sacral nerve root, which is easier to access than the distal pelvic nerve fibers within the abdominal cavity. We therefore investigated whether voiding could be inhibited by high-frequency stimulation at S1 and how this compared to distal pelvic nerve stimulation.Methods: Urethane-anesthetized rats were instrumented to record bladder pressure and abdominal wall electromyogram and to stimulate the distal preganglionic pelvic nerve bundle and S1 sacral root. Saline was infused continuously into the bladder to evoke repeated voiding. Stimulation was initiated within 1-2 sec of the onset of the steep rise in bladder pressure signaling an imminent void.Results: In six rats, stimulation of the distal pelvic nerve bundle (1-3 kHz sinusoidal waveform 1 mA, 60 sec) supressed the occurrence of an imminent void. Voiding resumed within 70 AE 13.0 sec (mean AE SEM) of stopping stimulation. Stimulation (using the same parameters) of the S1 root at the level of the sacral foramen suppressed voiding for the entire stimulation period in three rats and deferred voiding for 35-56 sec (mean 44.0 AE 3.2 sec) in the remaining three. Stimulation at either site when the bladder was approximately half full, as estimated from previous intervoid intervals, had no effect on voiding.Conclusions: This preliminary study provides proof-of-concept for the sacral root as an accessible target for high-frequency stimulation that may be developed as an "on demand" neuromodulation paradigm to suppress unwanted urinary voids.

Sacral Neuromodulation for Lower Urinary Tract and Bowel Dysfunction in Animal Models: A Systematic Review With Focus on Stimulation Parameter Selection

“…HF‐SNM at 1 or 3 kHz was reported to suppress imminent voids for 35–262 sec when SNM was applied for 60 sec after the onset of an imminent void. Bladder pressure continued to rise steeply after the SNM onset and reduced rapidly to a lower level for the remaining 60 sec SNM until a void occurred (17).…”

“…HF-SNM was reported to block or fatigue EUS pressure and allow voiding (14)(15)(16). At the same time, HF-SNM was reported to suppress acute imminent voids (17). All studies reported low bladder pressure when HF-SNM was applied.…”

“…HF-SNM at 1 or 3 kHz was reported to suppress imminent voids for 35-262 sec when SNM was applied for 60 sec after the onset of an imminent void. Bladder pressure continued to rise steeply after the SNM onset and reduced rapidly to a lower level for the remaining 60 sec SNM until a void occurred (17). The effect of different frequencies on bladder capacity in healthy and acetic acid (a.a.) induced overactive bladder (OAB) animals was investigated (6,7,11,18,19).…”

Sacral nerve stimulation for refractory OAB and idiopathic urinary retention: Can phenotyping improve the outcome for patients: ICI‐RS 2019?

“…46 Using this approach, stimulation at the sacral root was found to be as effective in suppressing imminent voids as stimulating the distal pelvic nerve bundle. 47 Thus, high-frequency (low kHz range) stimulation may have translational potential for SNS to suppress voids on-demand in some forms of urgency UI. The mode of action of low kHz pelvic nerve stimulation appears to be due to the activation of afferent fibers.…”

“…A more accessible surgical approach could be to access the pelvic nerve afferents as they enter the sacral cord (S1 in Wistar rats) . Using this approach, stimulation at the sacral root was found to be as effective in suppressing imminent voids as stimulating the distal pelvic nerve bundle . Thus, high‐frequency (low kHz range) stimulation may have translational potential for SNS to suppress voids on‐demand in some forms of urgency UI.…”