Abstract
This study used the Frankenhaeuser–Huxley axonal model to analyze the effects of non-symmetric waveforms on conduction block of myelinated axons induced by high-frequency (10–300 kHz) biphasic electrical stimulation. The results predict a monotonic relationship between block threshold and stimulation frequency for symmetric waveform and a non-monotonic relationship for non-symmetric waveforms. The symmetric waveform causes conduction block by constantly activating both sodium and potassium channels at frequencies of 20–300 kHz, while the non-symmetric waveforms share the same blocking mechanism from 20 kHz up to the peak threshold frequency. At the frequencies above the peak threshold frequency the non-symmetric waveforms block axonal conduction by either hyperpolarizing the membrane (if the positive pulse is longer) or depolarizing the membrane (if the negative pulse is longer). This simulation study further increases our understanding of conduction block in myelinated axons induced by high-frequency biphasic electrical stimulation, and can guide future animal experiments as well as optimize stimulation parameters that might be used for electrically induced nerve block in clinical applications.
Highlights
High-frequency biphasic electrical stimulation has recently been investigated extensively due to its potential clinical application to block peripheral nerve conduction (Nashold et al, 1982; Tai et al, 2004; Camilleri et al, 2009; Waataja et al, 2011)
This study using the Frankenhaeuser–Huxley axonal model successfully simulated nerve conduction block in myelinated axons during high-frequency (10–300 kHz) biphasic electrical stimulation (Figure 2). It predicted a monotonic relationship between block threshold and stimulation frequency for a symmetric waveform (Figure 3A) and a non-monotonic relationship for non-symmetric waveforms (Figures 3B,C)
The results reveal that the symmetric waveform causes conduction block by constantly activating both sodium and potassium channels (Figure 4) at frequencies of 20–300 kHz, while the non-symmetric waveforms share the same blocking mechanism as the symmetric waveform from 20 kHz up to the peak threshold frequency (Figure 5)
Summary
High-frequency (kHz) biphasic electrical stimulation has recently been investigated extensively due to its potential clinical application to block peripheral nerve conduction (Nashold et al, 1982; Tai et al, 2004; Camilleri et al, 2009; Waataja et al, 2011). Recent animal studies (Joseph and Butera, 2009, 2011) revealed that this monotonic relationship does not hold in small unmyelinated axons where the block threshold current only increases with frequency up to about 12–15 kHz and decreases as the stimulation frequency further increases. High-frequency nerve block what causes the difference of high-frequency block between myelinated and unmyelinated axons Answering this question will help to understand the mechanisms underlying nerve conduction block induced by high-frequency biphasic electrical stimulation
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