Coexistence of ipsilateral pain‐inhibitory and facilitatory processes after high‐frequency electrical stimulation

Abstract

Background High‐frequency electrical stimulation (HFS) of the human forearm evokes analgesia to blunt pressure in the ipsilateral forehead, consistent with descending ipsilateral inhibitory pain modulation. The aim of the current study was to further delineate pain modulation processes evoked by HFS by examining sensory changes in the arm and forehead; investigating the effects of HFS on nociceptive blink reflexes elicited by supraorbital electrical stimulation; and assessing effects of counter‐irritation (electrically evoked pain at the HFS‐conditioned site in the forearm) on nociceptive blink reflexes before and after HFS. Methods Before and after HFS conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the conditioned site in the forearm and on each side of the forehead. Nociceptive blink reflexes were also assessed before and after HFS with and without counter‐irritation of the forearm. Results HFS triggered secondary hyperalgesia in the forearm (a sign of central sensitization) and analgesia to blunt pressure in the ipsilateral forehead. Under most conditions, both HFS conditioning and counter‐irritation of the forearm suppressed electrically evoked pain in the forehead, and the amplitude of the blink reflex to supraorbital stimuli decreased. Importantly, however, in the absence of forearm counter‐irritation, HFS conditioning facilitated ipsilateral blink reflex amplitude to supraorbital stimuli delivered ipsilateral to the HFS‐conditioned site. Conclusions These findings suggest that HFS concurrently triggers hemilateral inhibitory and facilitatory influences on nociceptive processing over and above more general effects of counter‐irritation. The inhibitory influence may help limit the spread of sensitization in central nociceptive pathways.

Involvement of α2‐adrenoceptors in inhibitory and facilitatory pain modulation processes

“…Similar to previous studies (Lang et al., ; Klein et al., ; Pfau et al., ; Vo and Drummond, , ), hypersensitivity to sharpness and pressure‐pain developed at the HFS‐treated site (primary hyperalgesia), and hypersensitivity to sharpness also developed nearby (secondary hyperalgesia). In addition, heat hyperalgesia developed at the primary site, possibly because the electric current triggered release of prostaglandins (Ferrell et al., ; Tartas et al., ; Derow et al., ).…”

“…Sensitivity to blunt pressure decreased on both sides of the forehead after HFS, presumably due to inhibitory processes induced by heterotopic noxious conditioning stimulation or psychological stress. As noted previously (Vo and Drummond, , ), analgesia was greater on the ipsilateral side. We hypothesized that noradrenergic projections from the locus coeruleus to the ipsilateral medullary, and dorsal horn (Hitoto et al., ; Tsuruoka et al., , ) would mediate analgesia in the ipsilateral forehead.…”

“…Each electrical stimulus delivered in the supraorbital region elicited a clear blink reflex waveform (refer to Vo and Drummond, ). Consistent with Kaube et al.…”

“…In healthy humans, various forms of upper limb pain inhibit sensitivity to pain induced by blunt pressure in the forehead, particularly on the ipsilateral side (Knudsen and Drummond, , ; Vo and Drummond, , ). Studies in rats have identified an ipsilateral inhibitory pain modulation process involving noradrenergic projections from the locus coeruleus that stimulate spinal α 2 ‐adrenoceptors (Tsuruoka et al., , , ).…”

“…The aim of the present study was to determine whether α 2 ‐adrenoceptors mediate the ipsilateral analgesia that develops after high‐frequency electrical stimulation (HFS) of the human forearm (Vo and Drummond, , ). Specifically, HFS not only induces primary and secondary hyperalgesia at the site of stimulation in the forearm (Klein et al., , ; Pfau et al., ) but also triggers analgesia to pressure‐pain in the ipsilateral forehead (Vo and Drummond, , ). To investigate the role of α 2 ‐adrenoceptors in these nociceptive processes, the α 2 ‐adrenoceptor antagonist yohimbine was administered before HFS conditioning.…”