Suppression of Urinary Voiding by Conditional High Frequency Stimulation of the Pelvic Nerve in Conscious Rats

Abstract

Female Wistar rats were instrumented to record bladder pressure and to stimulate the left pelvic nerve. Repeated voids were induced by continuous infusion of saline into the bladder (11.2 ml/h) via a T-piece in the line to the bladder catheter. In each animal tested (n = 6) high frequency pelvic nerve stimulation (1–3 kHz, 1–2 mA sinusoidal waveform for 60 s) applied within 2 s of the onset of a sharp rise in bladder pressure signaling an imminent void was able to inhibit micturition. Voiding was modulated in three ways: (1) Suppression of voiding (four rats, n = 13 trials). No fluid output or a very small volume of fluid expelled (<15% of the volume expected based on the mean of the previous 2 or 3 voids). Voiding suppressed for the entirety of the stimulation period (60 s) and resumed within 37 s of stopping stimulation. (2) Void deferred (four rats, n = 6 trials). The imminent void was suppressed (no fluid expelled) but a void occurred later in the stimulation period (12–44 s, mean 24.5 ± 5.2 s after the onset of the stimulation). (3) Reduction in voided volume (five rats, n = 20 trials). Voiding took place but the volume of fluid voided was 15–80% (range 21.8–77.8%, mean 45.3 ± 3.6%) of the volume expected from the mean of the preceding two or three voids. Spontaneous voiding resumed within 5 min of stopping stimulation. Stimulation during the filling phase in between voids had no effect. The experiments demonstrate that conditional high frequency stimulation of the pelvic nerve started at the onset of an imminent void can inhibit voiding. The effect was rapidly reversible and was not accompanied by any adverse behavioral side effects.

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

“…The use of anesthesia in the present study is another possible confound. However, voiding evoked during continuous cystometry under urethane anesthesia is similar to that seen in conscious rats, differing principally with respect to the volume and frequency of voids . Most importantly for the present investigation, the inhibitory effect of pelvic nerve stimulation is also similar in anesthetized and conscious rats .…”

“…Devices for sacral nerve stimulation currently in clinical use are usually restricted to using continuously applied low (10's of Hz) frequencies, although a limited number of studies suggest that preprogrammed or patient‐operated schedules of intermittent stimulation may also be effective . Novel stimulation paradigms applied to the pelvic nerve using frequencies in the kHz range developed by us or using combinations of high and low frequencies have the potential to produce sophisticated and flexible modulation to target different types of voiding dysfunction. The functional response to high‐frequency stimulation of the S1 root and pelvic nerve described in the present study (total, immediate, and readily reversible suppression of imminent voids) differs from the functional response (increase in bladder capacity) produced by the low‐frequency stimulation regimens in clinical use.…”

“…The effect is rapid in onset, reproducible, and readily reversible. Voids could be similarly suppressed in chronically instrumented conscious rats without evoking any sign of discomfort or other adverse side effects .…”

Functional segregation within the pelvic nerve of male rats: a meso‐ and microscopic analysis

“…Efficacy of this approach for modulation of visceral function via the pelvic splanchnic nerves has been demonstrated (Kenefick et al 2003), however a strategy more specifically directed to the pelvic splanchnic nerves may be more successful for treating autonomic dysfunction or pain originating from the pelvic viscera. This more peripheral location for targeting neuromodulation shows considerable promise (de Groat and Tai, 2015;Brouillard et al 2018;Peh et al 2018) but remains under-explored, even though the pelvic splanchnic nerves are accessible through laparoscopic dissection (Possover et al 2007) and positioning of a neuromodulation device is feasible through a minimally invasive approach.…”

Estimation of Bladder Pressure and Volume from the Neural Activity of Lumbosacral Dorsal Horn Using a Long-Short-Term-Memory-based Deep Neural Network

“…Electrical stimulation to restore bladder functions can be applied continuously or conditionally 12–16 . Continuous stimulation may increase the risk of tissue damage due to the energy deployed during the stimulation and the risk of implanted electrode corrosion and may lead to habituation of the spinal reflexes.…”