周围神经损伤
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Figure 1｜Circuit models and stimulation waveforms.
Typical electrical stimulation patterns are trains of periodic pulses that are applied at stimulation rates between 20 and 100 Hz. The reported stimulation parameters in these clinical studies include only intensity, frequency, or pulse duration. We assume the stimulation pulses in most of these studies are rectangular, which invites the question: could other waveforms be more effective? The main difference between rectangular pulses and other waveforms is the distribution of power over the frequency domain, which can be derived by Fourier transform as the power spectral density. Studies of the impact of electric fields on synaptic plasticity suggest that the power spectral density of the stimulation train is likely to account for the majority of the impact on neural plasticity. Modeling indicates that the most probable direct effect of electrical stimulation is modulation of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (Figure 1). Although both of these channels are ligand-gated, they also have voltage and frequency dependent characteristics (Castellani et al., 2001). The equivalent circuit models of these ion channel receptors indicate that higher frequencies will induce a shunting current while lower frequencies will store transmembrane energy. We previously showed that voltage and frequency are inversely related due to the reactance of membrane capacitance (Chen et al., 2012). The significance of the power spectral density and the reactance of membrane capacitance indicate every aspect of the electrical stimulation parameters, including waveform, influence NMDA and AMPA ion channel receptor dynamics. As NMDA and AMPA receptors are present in peripheral glial cells, how is this relevant to electrical stimulation-promoted peripheral nerve regrowth?