High frequency electrical stimulation induces a long-lasting enhancement of event-related potentials but does not change the perception elicited by intra-epidermal electrical stimuli delivered to the area of increased mechanical pinprick sensitivity.

José Biurrun Manresa,Emanuel N Van Den Broeke,André Mouraux,Ole Kæseler Andersen,Claudia Sommer

doi:10.1371/journal.pone.0203365

Abstract

High frequency electrical stimulation (HFS) of the skin induces increased pinprick sensitivity in the surrounding unconditioned skin. The aim of the present study was to investigate the contribution of A-fiber nociceptors to this increased pinprick sensitivity. For this we assessed if the perception and brain responses elicited by low-intensity intra-epidermal electrical stimulation (IES), a method preferentially activating Aδ-fiber nociceptors, are increased in the area of HFS-induced increased pinprick sensitivity. HFS was delivered to one of the two forearms of seventeen healthy volunteers. Mechanical pinprick stimulation and IES were delivered at both arms before HFS (T0), 20 minutes after HFS (T1) and 45 minutes after HFS (T2). In all participants, HFS induced an increase in pinprick perception at the HFS-treated arm, adjacent to the site of HFS. This increase was significant at both T1 and T2. HFS did not affect the percept elicited by IES, but did enhance the magnitude of the N2 wave of IES-evoked brain potentials, both at T1 and at T2. Our results show that HFS induces a long-lasting enhancement of the N2 wave elicited by IES in the area of secondary hyperalgesia, indicating that HFS enhances the responsiveness of the central nervous system to nociceptive A-fiber input. However, we found no evidence that HFS affects the perception elicited by IES, which may suggest that the population of nociceptors that mediate the perception elicited by IES do not contribute to HFS-induced increased pinprick sensitivity.

Highlights

Cutaneous injury leads to increased pain sensitivity in the area of injury as well as the surrounding uninjured skin
Mouraux et al [16] showed that the perception and event-related brain potentials (ERPs) elicited by intra-epidermal electrical stimulation (IES) delivered at twice the absolute detection threshold are abolished in skin pre-treated with topical capsaicin to induce a reversible denervation of free nerve endings expressing the TRPV-1 receptor in the epidermal layer of the skin, while the perception and ERPs elicited by conventional transcutaneous electrical stimulation are preserved
The aim of the present study was to test whether the responses elicited by IES are increased in the area of increased mechanical pinprick sensitivity induced by High frequency electrical stimulation (HFS), and, to examine whether this enhancement correlates with the increase in pinprick perception

Summary

Introduction

Cutaneous injury leads to increased pain sensitivity in the area of injury (primary hyperalgesia) as well as the surrounding uninjured skin (secondary hyperalgesia; [1]). Mouraux et al [16] showed that the perception and event-related brain potentials (ERPs) elicited by IES delivered at twice the absolute detection threshold are abolished in skin pre-treated with topical capsaicin to induce a reversible denervation of free nerve endings expressing the TRPV-1 receptor in the epidermal layer of the skin, while the perception and ERPs elicited by conventional transcutaneous electrical stimulation are preserved They showed that IES does not elicit neither perception nor measurable brain responses when the stimuli are delivered during an A-fiber nerve conduction block, suggesting that C-fibers, which are unaffected by the block, do not significantly contribute to the responses elicited by IES. The aim of the present study was to test whether the responses elicited by IES are increased in the area of increased mechanical pinprick sensitivity induced by HFS, and, to examine whether this enhancement correlates with the increase in pinprick perception

Participants

Experimental procedure

Results

Discussion