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

PLoS One. 2018 Sep 6;13(9):e0203365. doi: 10.1371/journal.pone.0203365. eCollection 2018.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Conditioning, Psychological / physiology
  • Electric Stimulation / adverse effects*
  • Electric Stimulation / methods
  • Electroencephalography
  • Evoked Potentials, Somatosensory / physiology*
  • Female
  • Forearm
  • Humans
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology
  • Male
  • Nerve Fibers, Myelinated / physiology
  • Nociceptors / physiology
  • Pain Threshold / physiology
  • Perception / physiology
  • Physical Stimulation
  • Reaction Time / physiology
  • Skin / innervation*
  • Skin / physiopathology
  • Young Adult

Grant support

ENvdB and AM are supported by the European Research Council (ERC) “Starting Grant” (PROBING PAIN 336130). OKA and JBM are supported by the Danish National Research Foundation (DNRF121).