Poststimulation Block of Pudendal Nerve Conduction by High-Frequency (kHz) Biphasic Stimulation in Cats

Abstract

Objective To determine the relationship between various parameters of high‐frequency biphasic stimulation (HFBS) and the recovery period of post‐HFBS block of the pudendal nerve in cats. Materials and Methods A tripolar cuff electrode was implanted on the pudendal nerve to deliver HFBS in ten cats. Two hook electrodes were placed central or distal to the cuff electrode to stimulate the pudendal nerve and induce contractions of external urethral sphincter (EUS). A catheter was inserted toward the distal urethra to slowly perfuse the urethra and record the back‐up pressure generated by EUS contractions. After determining the block threshold (T), HFBS (6 or 10 kHz) of different durations (1, 5, 10, 20, 30 min) and intensities (1T or 2T) was used to produce the post‐HFBS block. Results HFBS at 10 kHz and 1T intensity must be applied for at least 30 min to induce post‐HFBS block. However, 10 kHz HFBS at a higher intensity (2T) elicited post‐HFBS block after stimulation of only 10 min; and 10 kHz HFBS at 2T for 30 min induced a longer‐lasting (1–3 h) post‐HFBS block that fully recovered with time. HFBS of 5‐min duration at 6 kHz produced a longer period (20.4 ± 2.1 min, p < 0.05, N = 5 cats) of post‐HFBS block than HFBS at 10 kHz (9.5 ± 2.1 min). Conclusion HFBS of longer duration, higher intensity, and lower frequency can produce longer‐lasting reversible post‐HFBS block. This study is important for developing new methods to block nerve conduction by HFBS.

Limited Sensitivity of Hippocampal Synaptic Function or Network Oscillations to Unmodulated Kilohertz Electric Fields

“…It is never possible to exclude β errors, though our use of a high SNR experimental system, with multiple slices and numerous repetitions per condition per slice, as well as within slice positive DC controls, together suggest such undetected effects would be variable or small in any case. Alternative mechanisms of electric fields such as ion concentration changes ( Bikson et al, 2001 ; Shapiro et al, 2020 ; Wang et al, 2020 ), fiber block ( Zhang et al, 2006 ; Zhao et al, 2014 ; Patel and Butera, 2015 ; Shapiro et al, 2020 ) and transverse axonal polarization ( Wang et al, 2018 ) are suggested for kHz stimulation at very high intensities. However these very high intensities are not expected in existing clinical applications, such as SCS, with targeted tissue some mm away from the electrode ( Lempka et al, 2015 ; Idlett et al, 2019 ).…”

Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance

“…We paused for > 2 s between amplitudes and > 5 s between each waveform and frequency pair. In addition to expediting the experiment, the short duration signals and low initial amplitudes also reduced the possibility of confounding carryover effects 18,39,40 , which were not observed in this study. In nerves 1-3, we terminated each binary search after identifying the minimum amplitude that blocked nerve conduction regardless of polarity, taking the block threshold only of the polarity that blocked at a lower threshold.…”

Pudendal Nerve Block by Low-Frequency (≤1 kHz) Biphasic Electrical Stimulation

“…This post‐HFBS block can reverse with time as the axonal membrane ion pump gradually restores the normal intra‐ and extra‐cellular ion concentrations. This theory can explain the post‐HFBS block shown in recent animal studies (7,8). However, based on this hypothesis, it is not necessary to use frequencies ≥5 kHz to produce the post‐HFBS block.…”

“…This eliminates the delay between the opening of sodium and potassium channels when a propagating action potential arrives at the site of HFBS, thereby preventing the generation of the action potential and causing a block of nerve conduction (9,10). However, this mechanism cannot explain the discovery in recent animal studies (7,8) that nerve block persists even after the end of HFBS because the potassium channels close quickly after terminating HFBS (10). However, our computer simulation studies (9,10) also revealed that when axonal ion channels remain open during HFBS each electrical pulse during stimulation generates large inward sodium and outward potassium currents.…”

“…HFBS has also been used clinically for spinal cord stimulation to treat chronic back and leg pain (6), although whether nerve block is the mechanism of pain suppression by spinal HFBS is still debatable. In addition to the block of nerve conduction during HFBS, animal studies (7,8) have shown that nerve block persists after the end of HFBS, that is, a post‐HFBS block. Despite significant progress in both clinical and basic science studies, the mechanism underlying HFBS‐induced nerve block is currently still unknown.…”