Neuromodulation methods have been introduced as treatment options for lower urinary tract dysfunction. These methods use different devices, stimulation parameters, and target different neural structures. While their clinical benefit has been confirmed, our understanding of their mechanism of action is limited. Furthermore, optimal stimulation parameters and treatment protocols remain unclear. Peroneal and tibial nerves are the two main branches of the sciatic nerve which originates from the lumbar spinal segments L4-L5 and the sacral spinal segments S1–S2. Neuromodulation using peroneal nerve stimulation has been recently developed and its efficacy in the treatment of overactive bladder was documented in early clinical trials. We hypothesized that, as with the tibial nerve, peroneal neurostimulation can suppress detrusor overactivity in a rat model of nociceptive bladder distension. Thus, the aim of this study was first, to develop surgical technique for exposure and stimulation of the peroneal nerve in anesthetized rats and second, to perform cystometry at baseline, during infusion of acetic acid before, during and immediately after peroneal nerve stimulation.

Male Sprague Dawley rats were implanted with an intravesical catheter five days prior to cystometry. Peroneal nerve was exposed through a skin incision between the knee and ischial tuberosity at the point of division of the sciatic nerve into the tibial, peroneal and sural nerves. A bipolar 125 µm Teflon-coated silver wire electrode for neurostimulation was placed under the nerve, secured and isolated from surrounding tissue using a biocompatible silicone glue (Figure 1). Subsequently, we assessed bladder function using anesthetized cystometry at baseline (during intravesical infusion of 0.9% NaCl) and during infusion of diluted acetic acid before, during and after peroneal nerve stimulation. Anesthesia with a full dose of ketamine and xylazine was used during the electrode implantation. It was reduced to one-sixth of the initial dose and administered every 10 minutes during cystometry using a canula placed intraperitoneal.

Reduced dose of ketamine and xylazine preserved micturition during cystometry.  Peroneal nerve stimulation induced rhythmic dorsal flection of the foot. Stimulation at the level of motor threshold (0.8 – 2V) using a frequency of 5Hz, resulted in an increase in the intermicturition interval from 258.1 ± 41.7 to 442.8 ± 55.0 (p ≤ 0.05) before and during neurostimulation respectively. Bladder pressure parameters are summarized in Figure 2. In subsequent experiments stimulation was performed at higher intensity (3x motor threshold) and frequency of 10 Hz. In addition to the effect described above, higher stimulation parameters resulted in an increased bladder compliance (Figure 3).

Cystometry prior to, during and post neurostimulation of the peroneal nerve in an anesthetized rat allows for study of the effect of peroneal neurostimulation on bladder function. The stimulation parameters tested in the first part of this study were chosen to reflect those currently used in clinical practice. Although a statistically significant increase in functional bladder capacity was observed, the difference between the bladder pressure parameters did not reach statistical significance. Applying higher stimulation parameters showed improvement in bladder compliance. This agrees with previously published animal studies which used stimulation of sacral or peripheral nerves and only detected an effect when an intensity of 3 – 6 times the motor threshold and frequency of 10 Hz were used.

The effect of the peroneal nerve stimulation on the lower urinary tract function can be studied in a rat model. This model could be used to optimize stimulation parameters and help elucidate the mechanism of action of this new treatment modality.

Krhut J, Rejchrt M, Slovak M, Dvorak RV, Peter L, Blok BFM, Zvara P. Prospective, Randomized, Multicenter Trial of Peroneal Electrical Transcutaneous Neuromodulation vs Solifenacin in Treatment-naïve Patients With Overactive Bladder. J Urol. 2023 Apr;209(4):734-741.

Continence 12S (2024) 101371
DOI: 10.1016/j.cont.2024.101371