In-vivo application of low frequency alternating currents on porcine cervical vagus nerve evokes reversible nerve conduction block

摘要

Electrical nerve conduction block provides a means to interrupt or subtractively modulate the neural activity within somatic or autonomic nerves. It has been shown to reduce spasticity via motor nerve block and modulate the activity of autonomic nerves (Kilgore and Bhadra 2014; Bhadra et al. 2006; Johannessen et al. 2017). Current techniques being investigated that have provided evidence of nerve conduction block include: kilohertz frequency alternating current block (kHFACb) (Kilgore and Bhadra 2014; Bhadra and Kilgore 2005; Bhadra et al. 2018; Patel and Butera 2015), direct current (DC) block (Whitwam and Kidd 1975; Bhadra and Kilgore 2004; Trenchard and Widdicombe 1973), anodal block (Rijkhoff et al. 1994; Thoren et al. 1977), and quasi-trapezoidal stimulation (Tosato et al. 2007; Fang and Mortimer 1991a; Fang and Mortimer 1991b; Fang and Mortimer 1991c). However, in many of these methods, side effects and shortcomings need to be addressed. DC block, for example, can result in toxic byproducts when the electrode potentials exceed the Water window resulting in hydrolysis and formation of hydronium cations and hydroxide anions. This has shown to not only irreparably injure tissues (Whitwam and Kidd 1975), but also causes electrode corrosion over time. The use of an alternating charge balanced current has the ability to reverse the Faradaic reactions in order to reduce the possibility of damaging byproduct formation. KHFACb is a method that uses a sinusoidal waveform with frequencies ranging from 1 kHz - 40 kHz (Kilgore and Bhadra 2014; Kilgore and Bhadra 2004). However, it has an associated onset response which causes the activation of nerve fibers before block can occur (Foldes et al. 2009), implicating an open state Na+ channel inactivation mechanism. A combination of DC block followed by kHFACb is a strategy used in which the DC waveform blocks the onset activation of kHFACb (Franke et al. 2014; Miles et al. 2007; Ackermann et al. 2011; Vrabec 2016).