High frequency electrical stimulation concurrently induces central sensitization and ipsilateral inhibitory pain modulation

Abstract

Background In healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead during various forms of limb pain. The aim of the current study was to determine whether this analgesic response is induced by ultraviolet B radiation (UVB), which evokes signs of peripheral sensitization, or by high‐frequency electrical stimulation (HFS), which triggers signs of central sensitization. Methods Before and after HFS and UVB conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the treated site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. The effect of ipsilateral versus contralateral temple cooling on electrically evoked pain in the forearm was then examined, to determine whether HFS or UVB conditioning altered inhibitory pain modulation. Results UVB conditioning triggered signs of peripheral sensitization, whereas HFS conditioning triggered signs of central sensitization. Importantly, ipsilateral forehead analgesia developed after HFS but not UVB conditioning. In addition, decreases in electrically evoked pain at the HFS‐treated site were greater during ipsilateral than contralateral temple cooling, whereas decreases at the UVB‐treated site were similar during both procedures. Conclusions HFS conditioning induced signs of central sensitization in the forearm and analgesia both in the ipsilateral forehead and the HFS‐treated site. This ipsilateral analgesia was not due to peripheral sensitization or other non‐specific effects, as it failed to develop after UVB conditioning. Thus, the supra‐spinal mechanisms that evoke central sensitization might also trigger a hemilateral inhibitory pain modulation process. This inhibitory process could sharpen the boundaries of central sensitization or limit its spread.

Analgesia to pressure–pain develops in the ipsilateral forehead after high- and low-frequency electrical stimulation of the forearm

“…Similarly, hyperalgesia to pinpricks and von Frey's monofilament developed at and around the HFSconditioned site, consistent with the development of central sensitisation (Klein et al 2008;Pfau et al 2011;Vo and Drummond 2013b, a;van den Broeke et al 2011;van den Broeke et al 2010). Central sensitisation is mediated, in part, by facilitatory influences on spinal nociception that emanate from the rostroventral medulla (Millan 2002;Sandkuhler 2009;Urban et al 1999;Pertovaara et al 1996;Burgess et al 2002).…”

“…In our previous study (Vo and Drummond 2013b), cold-evoked pain in the ipsilateral temple reduced electrically-evoked pain at the HFS-conditioned forearm site to a greater extent than cold-evoked pain in the contralateral temple, suggesting that HFS induced an ipsilateral pain-inhibitory influence on nociception in the forearm. In the present study, analgesia to pressure-pain in the ipsilateral forehead after electrical stimulation was associated with decreases in sensitivity to heat around the site of electrical stimulation, after changes in other sensory modalities had been taken into account.…”

“…Specifically, HFS of the forearm enhanced pain sensitivity to mechanical punctate stimuli (pinpricks and von Frey's monofilament) not only at the conditioned site but also in adjacent skin (Vo and Drummond 2013b, a), consistent with secondary hyperalgesia (a sign of central sensitisation) (Klein et al 2008;Pfau et al 2011). In addition, sensitivity to blunt pressure-pain decreased on both sides of the forehead, with a greater reduction on the ipsilateral side.…”

“…Thus, the central sensitisation triggered by HFS may be opposed, in part, by activation of descending pain modulation pathways. Generalisation of this inhibitory effect to other regions on the ipsilateral side of the body might account for the reduction in sensitivity to pressure-pain in the ipsilateral forehead (Vo and Drummond 2013b, a).…”

“…Rekindling heat hyperalgesia in capsaicin-sensitised forearm skin (Knudsen and Drummond 2011) and immersing a limb in ice-water (Knudsen and Drummond 2009) evokes this ipsilateral response, as does brief bursts of high-frequency electrical stimulation (HFS) to the forearm (Vo and Drummond 2013b, a). Specifically, HFS of the forearm enhanced pain sensitivity to mechanical punctate stimuli (pinpricks and von Frey's monofilament) not only at the conditioned site but also in adjacent skin (Vo and Drummond 2013b, a), consistent with secondary hyperalgesia (a sign of central sensitisation) (Klein et al 2008;Pfau et al 2011).…”