Combining direct current and kilohertz frequency alternating current to mitigate onset activity during electrical nerve block

Abstract

Objective. Electrical nerve block offers the ability to immediately and reversibly block peripheral nerve conduction and would have applications in the emerging field of bioelectronics. Two modalities of electrical nerve block have been investigated—kilohertz frequency alternating current (KHFAC) and direct current (DC). KHFAC can be safely delivered with conventional electrodes, but has the disadvantage of having an onset response, which is a period of increased neural activation before block is established and currently limits clinical translation. DC has long been known to block neural conduction without an onset response but creates damaging reactive species. Typical electrodes can safely deliver DC for less than one second, but advances in high capacitance electrodes allow DC delivery up to 10 s without damage. The present work aimed to combine DC and KHFAC into a single waveform, named the combined reduced onset waveform (CROW), which can initiate block without an onset response while also maintaining safe block for long durations. This waveform consists of a short, DC pre-pulse before initiating KHFAC. Approach. Simulations of this novel waveform were carried out in the axonal simulation environment NEURON to test feasibility and gain insight into the mechanisms of action. Two sets of acute experiments were then conducted in adult Sprague–Dawley rats to determine the effectiveness of the waveform in mitigating the onset response. Main results. The CROW reduced the onset response both in silico and in vivo. The onset area was reduced by over 90% with the tested parameters in the acute experiments. The amplitude of the DC pulse was shown to be particularly important for effective onset mitigation, requiring amplitudes 6–8 times the DC block threshold. Significance. This waveform can reliably reduce the onset response due to KHFAC and could allow for wider clinical implementation of electrical nerve block.

Effects of waveform shape and electrode material on KiloHertz frequency alternating current block of mammalian peripheral nerve

“…While sinusoidal waves only have a single frequency component, the triangle and square waves have an infinite series of higher harmonics, making the inclusion of a frequency-dependent membrane capacitance particularly significant. The relatively small difference between the voltage and state profiles across waveforms shows that there is a similar effect on the axon, leading to the constant activation of the sodium gate in a quasi-steady state as a common mechanism of block across waveforms (Eggers et al 2021 ; Ackermann et al 2011a ).…”

“…Carbon black has high charge capacitance properties and has been used to safely deliver DC to block nerves (Vrabec et al 2016 ; Vrabec et al 2019 ), and as part of a combined DC/KHFAC waveform to block KHFAC onset response (Eggers et al 2021 ). To date, there has not been a direct comparison of the KHFAC properties of carbon-black coating with bare metal electrodes.…”

“…Platinum foil was encased between two silicone sheets, and windows of 1 × 3 mm were cut to expose the platinum (Foldes et al 2011 ). Carbon black coating was applied as described previously (Eggers et al 2021 ; Goh et al 2022 ). Total charge capacity of each electrode window was determined in-vitro using cyclic voltammetry prior to in-vivo use (Vrabec et al 2019 ).…”

“…Recent advances in direct current nerve block have shown the usability of high capacitance or high surface area electrodes to reduce or eliminate irreversible Faradaic reactions and ensure nerve safety (Vrabec et al 2016 ). A recent publication demonstrates the use of a carbon monopolar electrode, using a combined direct current (DC) and KHFAC waveform to minimize the onset response (Vrabec et al 2013 ; Eggers et al 2021 ). However, one unanswered question is whether the KHFAC onset response using these newer electrodes differs from that produced using bare platinum electrodes.…”

A bioresorbable peripheral nerve stimulator for electronic pain block

“…The most effective approach uses electrodes in cylindrical cuff geometries to deliver kilohertz-frequency alternating current (KHFAC) (i.e., sinusoidal waveforms with an amplitude of 10 V pp and frequencies of 25 to 35 kHz as the optimal condition) directly to the peripheral nerves. The KHFAC stimulation maintains dynamic steady-state depolarization, thereby arresting action potentials in the axons that carry pain signals when they reach the depolarizing charge field (18,19). This scheme is attractive relative to TENS or PENS because it can reliably and completely block nerve conduction with response times less than 10 ms (19,20) that are much faster than these alternatives (seconds) (19,21).…”