Low Pressure Voiding Induced by Pudendal Nerve Stimulation and Block Using Lead Electrodes in Spinal Intact Cats

Chen J1, Jian J1, Wang J1, Shen Z1, Shen B1, Wang W1, Beckel J2, de Groat W2, Chermansky C1, Tai C1

Research Type

Pure and Applied Science / Translational

Abstract Category

Neurourology

Abstract 16
Live Pure and Applied Science 1 - Tiny Things for Big Effects
Scientific Podium Session 2
Thursday 14th October 2021
14:30 - 14:40
Live Room 1
Animal Study Neuromodulation Physiology
1. Department of Urology, University of Pittsburgh School of Medicine, 2. Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine
Presenter
C

Christopher J Chermansky

Links

Abstract

Hypothesis / aims of study
We have previously shown that detrusor sphincter dyssynergia (DSD) in spinal cord injured (SCI) cats can be blocked with high frequency, biphasic, bilateral stimulation of the pudendal nerves using cuff electrodes. Also, we showed that combining this block with lower frequency (30 Hz) unilateral pudendal nerve stimulation (PNS) resulted in low-pressure (≤50 cmH2O) voiding in SCI cats.  In this experiment, we sought to determine whether wire lead electrodes could be used to block and stimulate the pudendal nerve in spinal intact cats to achieve low-pressure voiding.
Study design, materials and methods
In anesthetized cats, wire lead electrodes were placed on both pudendal nerves. High frequency biphasic stimulation (1 kHz) was applied to block the nerve while 30 Hz stimulus pulses (0.2 ms) applied by a separate lead electrode located proximally on the nerve was used to elicit contractions of the external urethral sphincter (EUS) or induce a reflex bladder contraction. In 4 cats, a catheter was inserted into the distal urethra to perfuse and measure the increase in urethral pressure (IUP) caused by EUS contraction. In another 4 cats, intravesical pressure was measured via a catheter inserted into the bladder dome.
Results
The 1 kHz stimulation (30-60 secs, 0.5-5 mA) delivered via a wire lead electrode produced a complete post-stimulation block of PNS evoked IUP for ≥2 mins (see Figure 1) and a partial block lasting 6-18 minutes. The block duration lengthened after increasing either the intensity or duration of the kHz stimulation. Without the 1 kHz block, 30 Hz stimulation alone induced high-pressure (90 cmH2O) voiding (see Figure 2). When combined with the 1 kHz block, the 30 Hz stimulation induced low-pressure (≤50 cmH2O) voiding with a voiding efficiency of 80%.  During the prolonged period of pudendal nerve block there was no leakage of fluid from the bladder despite the finding of many small amplitude non-voiding contractions during this period.
Interpretation of results
In this study using spinal cord intact cats under anesthesia, we discovered that high frequency (1 kHz) biphasic electrical stimulation delivered by a wire hook electrode without a cuff could block pudendal nerve conduction during a short period immediately after termination of the stimulation, a post-stimulation block. In addition, low-pressure voiding could also be induced by applying 30 Hz pudendal nerve stimulation to induce a reflex bladder contraction during the post-stimulation block.   Because there was no leakage of fluid from the bladder during prolonged pudendal nerve block, basal urethral outlet resistance was maintained that prevented leakage from the bladder.  These results indicate that a minimally invasive surgical approach might be developed by inserting percutaneous lead electrodes close to the pudendal nerves to achieve pudendal nerve block to treat DSD after SCI.
Concluding message
This study demonstrated that the pudendal nerve in spinal intact cats can be successfully blocked by a lead electrode.  Furthermore, combining 1 kHz PNS, which blocks EUS contractions, and 30 Hz PNS, which stimulates the bladder, results in low-pressure voiding that is highly efficient.  For long-term clinical application, the safety of the 1 kHz block needs to be evaluated in a chronic animal study using a fully implantable device.
Figure 1
Figure 2
Disclosures
Funding Bridging the Gap Plus (BG+) program of the Defense Advanced Research Projects Agency (DARPA) under contract N66001-20-C-4050. Clinical Trial No Subjects Animal Species Cat Ethics Committee Animal Care and Use Committee at the University of Pittsburgh.
27/03/2024 13:27:01