High Frequency Stimulation of the Pelvic Nerve Inhibits Urinary Voiding in Anesthetized Rats

Abstract

Urge Urinary Incontinence: “a sudden and uncontrollable desire to void which is impossible to defer” is extremely common and considered the most bothersome of lower urinary tract conditions. Current treatments rely on pharmacological, neuromodulatory, and neurotoxicological approaches to manage the disorder, by reducing the excitability of the bladder muscle. However, some patients remain refractory to treatment. An alternative approach would be to temporarily suppress activity of the micturition control circuitry at the time of need i.e., urgency. In this study we investigated, in a rat model, the utility of high frequency pelvic nerve stimulation to produce a rapid onset, reversible suppression of voiding. In urethane-anesthetized rats periodic voiding was induced by continuous infusion of saline into the bladder whilst recording bladder pressure and electrical activity from the external urethral sphincter (EUS). High frequency (1–3 kHz), sinusoidal pelvic nerve stimulation initiated at the onset of the sharp rise in bladder pressure signaling an imminent void aborted the detrusor contraction. Urine output was suppressed and tone in the EUS increased. Stimulating the right or left nerve was equally effective. The effect was rapid in onset, reversible, and reproducible and evoked only minimal “off target” side effects on blood pressure, heart rate, respiration, uterine pressure, or rectal pressure. Transient contraction of abdominal wall was observed in some animals. Stimulation applied during the filling phase evoked a small, transient rise in bladder pressure and increased tonic activity in the EUS, but no urine output. Suppression of micturition persisted after section of the contralateral pelvic nerve or after ligation of the nerve distal to the electrode cuff on the ipsilateral side. We conclude that high frequency pelvic nerve stimulation initiated at the onset of an imminent void provides a potential means to control urinary continence.

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

“…The left pelvic nerve was then located and a miniature bipolar cuff electrode positioned on the preganglionic nerve bundle just proximal to the pelvic ganglion. The functional integrity of the nerve to bladder connection was confirmed by stimulating the nerve at low frequency (10 Hz, 1 mA for 10 sec) and observing a rise in bladder pressure, typically accompanied by a small rise in blood pressure (8–17 mmHg) as reported previously . The abdominal incision was then closed, and the bladder catheter and leads from the electrode exteriorised via the flank.…”

“…In each experiment, we first established that pelvic nerve stimulation inhibited voiding, as described previously . In every animal (6/6 rats), pelvic nerve stimulation was effective.…”

“…With the animal supine, the left femoral artery and left femoral vein were cannulated in order to measure blood pressure and for intravenous fluid replacement, respectively, as needed. A midline abdominal incision was made to expose the bladder and a polythene catheter inserted into the bladder through the dome and secured in place with 6.0 silk suture . The left pelvic nerve was then located and a miniature bipolar cuff electrode positioned on the preganglionic nerve bundle just proximal to the pelvic ganglion.…”

“…A sinusoidal waveform (0.5‑10 kHz) was used to deliver a charge balanced stimulus with an intensity of 1 or 2 mA. In a previous study, we had found these parameters to be optimal for inhibiting voiding by stimulating the pelvic nerve . EMG activity was amplified (5000x) and filtered 50‑5000 Hz using a Neurolog system (Digitimer Ltd, Welwyn Garden City, Hertfordshire, UK).…”

“…With these provisos in mind, we developed an animal model in which imminent voids can be suppressed on demand. In anesthetized rats, initiating high‐frequency (1‑3 kHz) stimulation of the pelvic nerve at the onset of the bladder contraction signaling an imminent void aborts the void and maintains urinary continence during the stimulation period . The effect is rapid in onset, reproducible, and readily reversible.…”