High-frequency electrical stimulation of the human skin induces heterotopical mechanical hyperalgesia, heat hyperalgesia, and enhanced responses to nonnociceptive vibrotactile input

J Neurophysiol. 2014 Apr;111(8):1564-73. doi: 10.1152/jn.00651.2013. Epub 2014 Jan 22.


High-frequency electrical stimulation (HFS) of the human skin induces increased pain sensitivity in the surrounding unconditioned skin. The aim of the present study was to characterize the relative contribution of the different types of nociceptive and nonnociceptive afferents to the heterotopical hyperalgesia induced by HFS. In 17 healthy volunteers (9 men and 8 women), we applied HFS to the ventral forearm. The intensity of perception and event-related brain potentials (ERPs) elicited by vibrotactile stimuli exclusively activating nonnociceptive low-threshold mechanoreceptors and thermonociceptive stimuli exclusively activating heat-sensitive nociceptive afferents were recorded before and after HFS. The previously described mechanical hyperalgesia following HFS was confirmed by measuring the changes in the intensity of perception elicited by mechanical punctate stimuli. HFS increased the perceived intensity of both mechanical punctate and thermonociceptive stimuli applied to the surrounding unconditioned skin. The time course of the effect of HFS on the perception of mechanical and thermal nociceptive stimuli was similar. This indicates that HFS does not only induce mechanical hyperalgesia, but also induces heat hyperalgesia in the heterotopical area. Vibrotactile ERPs were also enhanced after HFS, indicating that nonnociceptive somatosensory input could contribute to the enhanced responses to mechanical pinprick stimuli. Finally, the magnitude of thermonociceptive ERPs was unaffected by HFS, indicating that type II A-fiber mechano-heat nociceptors, thought to be the primary contributor to these brain responses, do not significantly contribute to the observed heat hyperalgesia.

Keywords: event-related potentials; heat; high-frequency stimulation; mechanical; secondary hyperalgesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / physiology*
  • Electric Stimulation
  • Evoked Potentials, Somatosensory / physiology*
  • Female
  • Forearm
  • Hot Temperature
  • Humans
  • Hyperalgesia / physiopathology*
  • Male
  • Pain Perception / physiology*
  • Physical Stimulation
  • Skin Physiological Phenomena*
  • Touch Perception / physiology*
  • Young Adult