The Crucial Role of Nerve Depolarisation in High Frequency Conduction Block in Mammalian Nerves: Simulation Study

Abstract

Neurostimulations which use High Frequency (HF) block show great promise for neuromodulatory therapies. Treatments have been developed for various health conditions including obesity and obesity related health risks, and now even stomach cancer treatments are being considered. However the mechanism of the block is still not completely clear, as well as how various neural and electrode parameters affect it. In order to study conduction block during HF stimulation in mammalian axons, we describe a detailed computational model and perform comprehensive simulations. We establish relationships between the blocking frequency and amplitude versus fibre diameter and the distance between the electrode and fibre. We found that only a certain level of depolarisation will universally create a block irrespective of the fibre size, and it is in the range 24-30 mV depending on the stimulus frequency. Our study crucially improves our knowledge about this important technique which is rapidly emerging as a commercially available therapy.

HFAC Dose Repetition and Accumulation Leads to Progressively Longer Block Carryover Effect in Rat Sciatic Nerve

“…To the authors' knowledge there does not currently exist any computational model of nerve that captures HFAC block carryover, or could explain such a process. In previous simulation work (Rapeaux et al, 2015 ; Perra et al, 2018 ), nerve fibres with mammalian and amphibian ion channel dynamics both recovered within milliseconds of the block signal being removed. Established models of nerve such as in Frankenhaeuser and Huxley ( 1964 ); McNeal ( 1976 ), and McIntyre et al ( 2002 ) used in HFAC block simulation studies such as Zhang et al ( 2006 ); Yu et al ( 2008 ); Zhang et al ( 2015 ); Zhao et al ( 2015 ), and Pelot et al ( 2017 ) have never reported observing block carryover in-silico .…”

“…One such mechanism is so-called “block carryover”, as reported in Waataja et al ( 2011 ); Liu et al ( 2013 ); Bhadra et al ( 2017 ); Yang et al ( 2017 ), and Pelot and Grill ( 2020 ), describing a process by which nerve excitability remains suppressed after application of HFAC block. This effect is not captured by computational simulations of nerve cells being stimulated by high-frequency signals (Ackermann et al, 2011 ; Liu et al, 2013 ; Pelot et al, 2017 ; Perra et al, 2018 ), requiring characterization before HFAC stimulation can be used in a clinical context. Furthermore, previous experimental work with HFAC has not always observed carryover block (Kilgore and Bhadra, 2004 ), indicating that the conditions in which carryover block occurs may be unclear and require clarification.…”