A Simulation Study on Selective Stimulation of C-Fiber Nerves for Chronic Pain Relief

Abstract

It has been reported that stimulating nociceptive unmyelinated C nerves (C) near the sarcolemma could induce the secretion of endogenous opioids that relieve chronic pain. However, a substantial concern remains: concomitant stimulation might cause acute pain to nociceptive myelinated Aδ nerves (Aδ), which generally have a lower activation threshold than the C. However, few studies have reported on C selectivity over Aδ (C-selectivity). In this study, the C and Aδ nerves were modeled using the Hodgkin-Huxley (HH) and McIntyre-Richardson-Grill (MRG) models, respectively. Two potential stimulation schemes, including bipolar square waves and burst modulated alternating current, together with a new stimulation scheme named inhibit-Aδ (i-Aδ) that inhibits the excitability of the Aδ, were systematically investigated. Their stimuli were given to the C and Aδ nerves through point electrodes located near the nerve fibers. Simulation results revealed that i-Aδ presented the highest C-selectivity, which provides a basis for non-invasive effective chronic-pain relief.

Ion mechanism and parameter analysis of anodal-first waveforms for selective stimulation of C-fiber nerves

“…It is necessary to trade off the C -selectivity effect and safety when performing stimulation below 15 Hz. Though, as reported by the other studies [Siyu He, 2020, 14], in the higher frequency band (100-500 Hz), however, the frequency turns to be an important factor to promote the excitation of Aδ while inhibiting C .…”

“…Both models were implemented in Matlab 2013a, with the 4th-order Runge–Kutta (RK4) as the numerical method to solve the differential equations of the HH and MRG models. The unmyelinated and myelinated nerve models were validated with animal experimental data [Siyu He, 2020, 14].…”

“…acupuncture electrodes) are inserted to specific spots that have higher spatial distribution of the C [Otsuru 2009, 13]. Since using acupuncture electrodes for stimulation requires professional skills, it is difficult to promote to the public use for chronic pain relief [Siyu He 2020, 14]. The laser and heat stimulation have been widely used in the laboratory-based C stimulation for pain-related clinical studies [Plaghki, Léon 2003, Churyukanov, Maxim 2012, 8–9].…”

“…Our hypothesis is that, the mechanism of anode break might work to further lower the threshold of C , too. In our previous study, we clarified that a low-frequency bipolar square waveform could improve the C -selectivity [Siyu He, 2020, 14]. However, neither the mechanism of the preceding anodal stimulation for the C -selectivity, nor the important parameters of the bipolar square wave have been explored.…”

Granger Causality-Based Pain Classification Using EEG Evoked by Electrical Stimulation Targeting Nociceptive Aδ and C Fibers

“…For example, sine waves with frequencies of 250 Hz and 5 Hz in a Neurometer (Neurotron, Baltimore, MD, USA) were used to stimulate Aẟ and C fibers, respectively, to measure their current perception threshold (CPT) [11]. New stimulation schemes have also been explored, mostly in simulation studies [12][13][14]. Although there has been evidence showing the effects of selective electrical stimulation on human subjects [15][16], the brain regions encoding painrelated information were not decisive.…”