Abstract

Electrical stimulation of specific small fibers (Aδ- and C-fibers) is used in basic studies on nociception and neuropathic pain and to diagnose neuropathies. For selective stimulation of small fibers, the optimal stimulation waveform parameters are an important aspect together with the study of electrode design. However, determining an optimal stimulation condition is challenging, as it requires the characterization of the response of the small fibers to electrical stimulation. The perception thresholds are generally characterized using single-pulse stimulation based on the strength-duration curve. However, this does not account for the temporal effects of the different waveforms used in practical applications. In this study, we designed an experiment to characterize the effects of multiple pulse stimulation and proposed a computational model that considers electrostimulation of fibers and synaptic effects in a multiscale model. The measurements of perception thresholds showed that the pulse dependency of the threshold was an exponential decay with a maximum reduction of 55%. In addition, the frequency dependence of the threshold showed a U-shaped response with a reduction of 25% at 30 Hz. Moreover, the computational model explained the synaptic effects, which were also confirmed by evoked potential recordings. This study further characterized the activation of small fibers and clarified the synaptic effects, demonstrating the importance of waveform selection.

Highlights

  • The central nervous system receives somatosensory information from different receptors and peripheral nerve fibers, which are integrated by synaptic processes

  • The synaptic effect generated a reduction of the threshold by 2.3 times for multiplepulse stimulation of five or more consecutive pulses to a single pulse

  • We hypothesized that a train of pulses can modify the perception threshold via synaptic effects

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Summary

Introduction

The central nervous system receives somatosensory information from different receptors and peripheral nerve fibers, which are integrated by synaptic processes. The present study aimed to measure and characterize the effects of stimulation of a train of pulses on the perception threshold via stimulation of Aδ-fibers in vivo for the first time. Stimulation of Aδ-fibers and synaptic effects were confirmed by the reaction time and evoked potential measurements.

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