Pelvic Nerve Stimulation for Urinary Urge Incontinence

Pelvic Nerve Stimulation for Urinary Urge Incontinence

Principal Investigator: University of Bristol

Co-Investigator: University of Aarhus, Denmark

With preliminary funding from IMPRESS we showed in urethane-anaesthetised rats that high frequency stimulation of the pelvic nerve could block urinary voiding that was induced every few minutes by continuous infusion of saline in the bladder. Initiating high frequency (1-3kHz sinusoidal waveform, 1-3mA for 60s) stimulation of the pelvic nerve unilaterally within 1-2 s of the onset of an imminent void (signalled by a rapid increase in bladder pressure) aborted the void and urinary continence was maintained during the stimulation period (Fig 1). Voiding resumed within a minute of stopping the stimulation. There were minimal ‘off target’ changes in blood pressure, heart rate, respiration, uterine or rectal pressure.

Fig 1. Effect of high frequency pelvic nerve stimulation (grey) panel on voiding and external urethral sphincter (EUS) activity evoked by continuous infusion of saline into the bladder. A. Initiating stimulation at the onset of a void aborted the void and no urine escaped. Voiding resumed within 20s of terminating the stimulation. B. Excerpt of the recordings at expanded time base shows development of bursting activity in the EUS during spontaneous voids. C pelvic nerve stimulation at the onset of an imminent void evoked tonic activity in the EUS. D Stimulation of the pelvic nerve in between voids evoked tonic contraction of EUS.

This initial study provided proof of concept for pelvic nerve stimulation as a means to control voiding. Now we need to make a detailed characterisation of the optimal stimulation parameters for inhibiting voiding and to identify of the best type of electrode for stimulation. This work will prepare the way for translating the results obtained under terminal anaesthesia to a conscious rat model in which we will investigate the effectiveness of intermittent pelvic nerve stimulation using electrodes that have been implanted for a period of weeks.

The next stage will be to adopt a model that more closely resembles humans. The pig is ideal in this respect. Initially we will carry out a proof of concept study under terminal anaesthesia to replicate the findings in rats. We will investigate the effectiveness of high frequency pelvic nerve stimulation on voiding activity evoked by infusion of saline into the bladder. We will conduct this work in collaboration with urological colleagues in the Department of Clinical Medicine, University of Aarhus, Denmark who have expertise in pig work. I have visited Aarhus and was impressed by the excellent facilities for working on pigs.

Although outside the scope of this follow-on application, the long-term goal is to translate the procedure to a conscious pig model with fully implanted stimulating device and bladder pressure sensor to detect imminent voids. Ultimately we wish to produce an implantable pelvic nerve stimulation device for patients with intractable urinary urge incontinence. The device would be operated by the patient at the onset of urge sensation to block voiding and ‘buy time’ for the individual to reach a toilet or other suitable place to void. The stimulation could then be switched off to permit voiding to take place.