Activation of peripheral nerve fibers by electrical stimulation in the sole of the foot

Abstract

BackgroundHuman nociceptive withdrawal reflexes (NWR) can be evoked by electrical stimulation applied to the sole of the foot. However, elicitation of NWRs is highly site dependent, and NWRs are especially difficult to elicit at the heel. The aim of the present study was to investigate potential peripheral mechanisms for any site dependent differences in reflex thresholds.ResultsThe first part of the study investigated the neural innervation in different sites of the sole of the foot using two different staining techniques. 1) Staining for the Nav1.7 antigen (small nociceptive fibers) and 2) the Sihler whole nerve technique (myelinated part of the nerve). No differences in innervation densities were found across the sole of the foot using the two staining techniques: Nav1.7 immunochemistry (small nociceptive fibers (1-way ANOVA, NS)) and the Sihler’s method (myelinated nerve fibers (1-way ANOVA, NS)). However, the results indicate that there are no nociceptive intraepidermal nerve fibers (IENFs) innervating the heel.Secondly, mathematical modeling was used to investigate to what degree differences in skin thicknesses affect the activation thresholds of Aδ and Aβ fibers in the sole of the foot. The modeling comprised finite element analysis of the volume conduction combined with a passive model of the activation of branching cutaneous nerve fibers. The model included three different sites in the sole of the foot (forefoot, arch and heel) and three different electrode sizes (diameters: 9.1, 12.9, and 18.3 mm). For each of the 9 combinations of site and electrode size, a total of 3000 Aβ fibers and 300 Aδ fibers was modeled. The computer simulation of the effects of skin thicknesses and innervation densities on thresholds of modeled Aδ and Aβ fibers did not reveal differences in pain and perception thresholds across the foot sole as have been observed experimentally. Instead a lack of IENFs at the heel decreased the electrical activation thresholds compared to models including IENFs.ConclusionsThe nerve staining and modeling results do not explain differences in NWR thresholds across the sole of the foot which may suggest that central mechanisms contribute to variation in NWR excitability across the sole of the foot.

Nerve Fiber Activation During Peripheral Nerve Field Stimulation: Importance of Electrode Orientation and Estimation of Area of Paresthesia

“…Throughout this study, the Aβ fibers had lower thresholds than Aδ fibers, which fits well with previous data . Furthermore, the area of activated nerve fibers was larger for Aβ fibers than for Aδ fibers, showing that PNFS will predominantly activate Aβ fibers.…”

“…The explicit morphology of the cutaneous part of the Aβ and Aδ fibers was implemented to study the size of the receptive field of the fibers and investigate how the morphology of the nerves affects the threshold. The morphology was similar to a previous study from our group (16). However, the intraepidermal nerve fibers were not modeled, as these are less important in implanted subcutaneous stimulation than in cutaneous stimulation and constitute a significant computational burden (12).…”

Thresholds of skin sensitivity are partially influenced by mechanical properties of the skin on the foot sole

“…) and was not able to explain site differences in the perception of electrical stimulation and afferent electrical activation thresholds (Frahm et al. ). The results of the latter two studies do not follow a similar causal trend to our work, which may not be surprising given that spatial information (two‐point discrimination) and electrical stimulation thresholds are perceptually different from light touch (MF).…”

“…; Craig ; Frahm et al. ). In contrast, MF threshold is mediated by baseline activity of FAI afferents (Johansson and Vallbo ).…”

Stimulation site and phase modulation of the withdrawal reflex during gait initiation

“…However, recent evidence indicates that when stimulating the sole of the foot, Ad fibers were activated within the most superficial 100 lm of the dermis while Ab fibers were activated throughout the dermis (Frahm et al, 2013a). Furthermore, the current flow between the stimulating and reference electrodes happened primarily through the dermis, with much smaller current densities in the fat, muscle, and bone layers (Frahm et al, 2013b) suggesting that even in both extreme conditions (fully loading/unloading of the foot) the current flow will most likely cause depolarization of the same fibers.…”