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SUFU 2022: The Bladder Inhibitory Effects of Saphenous Nerve Stimulation are Mediated Via A Supraspinal Pathway in Anesthetized Rodents

(UroToday.com) Peripheral nerve stimulation techniques are emerging as an effective alternative to existing therapies for overactive bladder (OAB). As a novel approach, saphenous nerve (SAFN) stimulation is being investigated as a method of electrically modulating bladder function. Published work showed that SAFN stimulation in urethane-anesthetized rats can significantly decrease the bladder contraction rate (BCR), while longer duration stimulation trials elicited episodes of overflow incontinence (OI).

However, the mechanistic pathway that mediates the inhibitory effects of SAFN stimulation on bladder function is unknown. In a small (n=18, female 55-84yrs) feasibility study by MacDiarmid (2018), percutaneous SAFN stimulation showed significant improvement in OAB symptoms along with clinically meaningful improvements in quality-of-life measures. This study investigated the mechanistic pathway by which SAFN stimulation evokes inhibitory bladder responses in anesthetized rodents. The hypothesis was that SAFN stimulation evokes bladder inhibition through a supraspinal mechanism.

Bladder function was quantified by changes in the BCR and the incidence rate of OI. OI was defined by (1) absence of reflex bladder contractions and bursting urethral sphincter EMG activity and (2) an elevated bladder pressure.

Non-survival experiments were performed in Long Evans rats, separated into a control group (healthy, 281 ± 14 g, n = 10) and a chronic spinal cord injury (SCI) group (complete transection at T7, 271 ± 24 g, n = 14). Under urethane anesthesia, each animal was instrumented with a suprapubic catheter to provide continuous infusion of saline (rate = 0.1 ml/min). A pair of stainless steel wires were inserted paraurethrally to target the urethral sphincter muscle and a bipolar nerve cuff electrode was implanted on the surgically dissected SN. Once stable reflex bladder contractions were confirmed (baseline), SN stimulation was applied intermittently in 40 min cycles (30 Min ON + 10 min OFF) and changes in bladder function were recorded.

Reflex bladder contractions were achieved in 10 control and 10 SCI animals during baseline. Repeated SN stimulation elicited OI episodes in 70% of experiments, along with a 26.6% decrease in BCR in the control (healthy) animals. In contrast, SN stimulation failed to elicit OI in any of the SCI rats, while changes in BCR were significantly smaller when compared to control animals (8.1 %, t-test p<0.05). The observed decrease in BCR suggests an increase in the bladder volume threshold at which reflex contractions are initiated. The high incidence rate of OI (70%) achieved in this study was comparable to previous work that delivered multiple SAFN stimulation trials at relatively lower amplitudes (50μA and 100μA) but longer durations (40 minutes).

The results of this study provide first preclinical evidence that the bladder inhibitory effects of SN stimulation involve a supraspinal mechanistic pathway in rodents, therefore suggesting a functional connection between the lumbar spinal cord and the brainstem (e.g., pontine micturition center).

Presented by: Grant Gruenspan,1 Jian Wang,2 Laureen Hachem,2 Michael Fehlings,2 Paul Yoo1

  1. Institute of Biomedical Engineering, University of Toronto, Canada
  2. Division of Neurosurgery, Krembil Neuroscience Centre, Toronto Western Hospital, University Health Network, Canada

Written by: Diane K. Newman, DNP, ANP-BC, FAAN, Adjunct Professor of Urology in Surgery, Perelman School of Medicine, University of Pennsylvania and Co-Director of the Penn Center for Continence and Pelvic Health at the 2022 Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) Winter Meeting, February 22 - 26, 2022

Funding: MITACS Accelerate Fellowship and EBT Medical

References:

  1. Franz, KS & Yoo, PB. Transecting the hypogastric nerve to uncover the bladder-inhibitory pathways involved with saphenous nerve stimulation in anesthetized rats. Auton Neurosci. 2020 Jul;226:102672.  doi: 10.1016/j.autneu.2020.102672. 
  2. MacDiarmid, SA, John, MS, Yoo, PB .A pilot feasibility study of treating overactive bladder patients with percutaneous saphenous nerve stimulation. Neurourol Urodyn, 2018 Jun;37(5):1815-1820. doi: 10.1002/nau.23531
  3. Moazzam Z, Yoo PB. Frequency-dependent inhibition of bladder function by saphenous nerve stimulation in anesthetized rats. Neurourol Urodyn. 2018 Feb;37(2):592-599. doi: 10.1002/nau.23323. Epub 2017 Jun 22.PMID: 2864044
  4. Moazzam Z, Yoo PB. Electrical stimulation of the saphenous nerve in anesthetized rats: a novel therapeutic approach to treating overactive bladder. Annu Int Conf IEEE Eng Med Biol Soc. 2016 Aug;2016:3125-3128. doi: 10.1109/EMBC.2016.7591391.PMID: 28268971