Reversible conduction block in peripheral nerve using electrical waveforms

Abstract

Introduction: Electrical nerve block uses electrical waveforms to block action potential propagation.

Materials & methods: Two key features that distinguish electrical nerve block from other nonelectrical means of nerve block: block occurs instantly, typically within 1 s; and block is fully and rapidly reversible (within seconds).

Results: Approaches for achieving electrical nerve block are reviewed, including kilohertz frequency alternating current and charge-balanced polarizing current. We conclude with a discussion of the future directions of electrical nerve block.

Conclusion: Electrical nerve block is an emerging technique that has many significant advantages over other methods of nerve block. This field is still in its infancy, but a significant expansion in the clinical application of this technique is expected in the coming years.

Keywords: action potential; direct current; electrical nerve block; kilohertz frequency; neuromodulation; neuroprosthesis.

Figure 1.. Typical in vivo setup for testing electrical nerve block.

The blocking electrode is placed between two stimulating electrodes on the rat sciatic nerve. Compound action potentials or force from the gastrocnemius muscle are measured to evaluate conduction block in the nerve. Distal stimulation is used to verify the physical location of block and assess the conduction properties of the nerve. CAP: Compound action potential; DS: Distal stimulation; ENB: Electrical nerve block; FT: Force transducer; PS: Proximal stimulation.

Figure 2.. Kilohertz frequency alternating current block of the rat sciatic nerve with a sinusoidal waveform at 30 KHz.

Supramaximal stimulation proximal to the block site is applied to produce gastrocnemius muscle contractions generated at 0.5 Hz, as indicated by the red arrows. KHFAC block is delivered starting at 7 s (green up arrow) and is turned off 30 s later (green down arrow). There is an initial onset response when the KHFAC begins. Immediately after the cessation of KHFAC, gastrocnemius twitch height returns to preblock levels. KHFAC: Kilohertz frequency alternating current.

Figure 3.. The effect of standard stimulation (20Hz used as an example) compared with the effect of kilohertz frequency alternating current on nerves.

This comparison focuses on the waveform amplitude versus the duration of the waveform delivery space. Within the amplitude-duration space, 20Hz has three known effects on the nerve: no action; activation (at an identifiable threshold); and damage. By contrast, in this same parameter space, KHFAC has at least nine possible ‘effect states’, including activation, block and many longer-term effects. Note that many of these possible effect states are theoretical and have not been experimentally demonstrated. Many of the exact borders and transitions between these effect states are also, as yet, unexplored, with the exception of the transition into the conduction block region. Future research may also reveal additional effects that are currently unknown. KHFAC: Kilohertz frequency alternating current.

Figure 4.. An example of slow recovery from carry-over block effect after application of kilohertz frequency alternating current for 2 h.

The PS/DS ratio is the ratio of twitch forces produced by test stimulation proximal and distal to the site of conduction block and is an index of residual nerve block and recovery. COBE: ‘Carry-over’ block effect; DS: Distal stimulation; KHFAC: Kilohertz frequency alternating current; PS: Proximal stimulation.

Figure 5.. Enhanced carbon-based separated interface nerve electrode can provide block safely for 50 min.

The SINE is turned off after 50 min and conduction recovery begins 5 min after cessation of block. Full recovery of nerve conduction occurs 20 min after cessation of block. SINE: Separated interface nerve electrode.

Figure 6.. Change in proximal stimulation/distal stimulation ratio for different electrode chemistries.

The nerve response degrades with bare platinum after approximately 70 mC of charge delivery, whereas the nerve response is maintained at 100% for PtBlack and IRO₂. IRO2: Iridium oxide; PtBlack: Platinum black.

Figure 7.. A four-contact electrode was used to maintain charge-balanced polarizing current block continuously by cycling through each contact.

Block was applied continuously for 22 min. Stimulation was applied at 1 Hz throughout the 22-min period. Occasionally, action potentials can pass through the blocked region, typically during the transition of block from one contact to another (see occasional twitches during block period, as shown in blue). At the end of the block period, there is a slight carry-over of the block effect, as indicated by the decrease in the PS/DS ratio from 1.0 prior to block to 0.9 after block. CBPC: Charge-balanced polarizing current; DS: Distal stimulation; PS: Proximal stimulation.

Figure 8.. Unifying theory of electrical nerve conduction block showing results from computer simulations.

The waveform varies from (left to right) anodal DC, anodal monophasic pulses, charged-balanced alternating current, cathodal monophasic pulses and cathodal DC, as shown below the x-axis (black = anodic; red = cathodic). There are three regions of block: hyperpolarizing, alternating current and depolarizing. The graph indicates the block threshold for each waveform along the continuum. Three insets along the top of the graph illustrate transmembrane voltage with the axonal length along the x-axis. Depolarization is upwards. On the left is ‘virtual depolarization block’, in the center is ‘KHFAC block from dynamic depolarization’ and on the right is ‘true depolarization block’. DC: Direct current; KHFAC: Kilohertz frequency alternating current.

Figure 9.. Example of combined direct current and kilohertz frequency alternating current block with separate electrodes.

KHFAC is the first to be tested alone to evaluate KHFAC onset. Next the DC is added to block the onset. KHFAC is then applied again alone to verify that the KHFAC onset had remained constant. DC: Direct current; KHFAC: Kilohertz frequency alternating current.

Figure 10.. In vivo results of the combined no onset waveform that initiates block with a pure direct current depolarization ramp and then gradually mixes in the kilohertz frequency alternating current before terminating the direct current with another ramp.

The ramps prevent any onsets from the DC. A 7 mA 20 KHz sine wave was applied to the nerve which generated an onset (arrow) with a peak force of 13.5 N (top). The DC block threshold was determined to be -1.4 mA. A DC signal at this level was added to the KHFAC signal (bottom blue trace in each figure). This mitigation strategy reduced the onset peak force to 3.0 N (middle, arrows). The KHFAC signal was set to 7 mA and the ramp to DC and the ramp to recharge were increased. This further decreased the peak onset to 0.4 N (bottom). The CNOW mitigation successfully reduced the onset to 3% of the peak force compared with the KHFAC alone. CNOW: Combined no onset waveform; DC: Direct current; KHFAC: Kilohertz frequency alternating current.