Central Sensitization of Mechanical Nociceptive Pathways Is Associated with a Long-Lasting Increase of Pinprick-Evoked Brain Potentials.

Emanuel N Van Den Broeke,Gan Huang,André Mouraux,Julien Lambert

doi:10.3389/fnhum.2016.00531

Emanuel N Van Den Broeke, Gan Huang + Show 2 more

Open Access

https://doi.org/10.3389/fnhum.2016.00531

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Abstract

Intense or sustained nociceptor activation, occurring, for example, after skin injury, can induce “central sensitization,” i.e., an increased responsiveness of nociceptive neurons in the central nervous system. A hallmark of central sensitization is increased mechanical pinprick sensitivity in the area surrounding the injured skin. The aim of the present study was to identify changes in brain activity related to this increased pinprick sensitivity. In 20 healthy volunteers, increased pinprick sensitivity was induced using high frequency electrical stimulation of the forearm skin (HFS). Mechanical pinprick stimulation (64 and 90 mN) was used to elicit event-related brain potentials (ERPs). The recordings were performed before, 20 min after and 45 min after applying HFS. The contralateral non-sensitized arm served as control. Pinprick stimulation of 64 mN, but not 90 mN, applied in the area of increased pinprick sensitivity elicited a significant increase of a late-latency positive wave, between 300 and 1100 ms after stimulus onset and was maximal at midline posterior electrodes. Most importantly, this increase in EEG activity followed the time course of the increase in pinprick perception, both being present 20 and 45 min after applying HFS. Our results show that the central sensitization of mechanical nociceptive pathways, manifested behaviorally as increased pinprick sensitivity, is associated with a long-lasting increase in pinprick-evoked brain potentials provided that a 64 mN stimulation intensity is used.

Highlights

Injury to the skin leads to increased pain sensitivity of the injured skin (“primary hyperalgesia”) and of the surrounding uninjured skin (“secondary hyperalgesia”)
In a previous study conducted using a range of pinprick intensities (16–512 mN) and a constant 0.25 mm tip diameter, we found that the brain responses elicited at intermediate pinprick intensities (64 mN) showed the strongest enhancement after the induction of secondary hyperalgesia
high frequency electrical stimulation (HFS) induced a clear increase in pinprick sensitivity on the treated arm, as shown by the changes in the intensity of the percept elicited by 64 and 90 mN pinprick stimulation (Figure 3)

Summary

Introduction

Injury to the skin leads to increased pain sensitivity of the injured skin (“primary hyperalgesia”) and of the surrounding uninjured skin (“secondary hyperalgesia”). A hallmark of secondary hyperalgesia is increased sensitivity to mechanical nociceptive stimuli such as pinprick stimuli (Raja et al, 1984; Ali et al, 1996; Magerl et al, 1998). The development of this increased pinprick sensitivity does not necessarily require tissue injury, as it can be induced experimentally by activating nociceptors in a sustained and intense fashion, for example, using high frequency electrical stimulation of the skin (Henrich et al, 2015) or intradermal injection of capsaicin (LaMotte et al, 1991; Ziegler et al, 1999; Magerl et al, 2001). The increase in pinprick sensitivity in the area of secondary hyperalgesia is thought to predominantly result from central sensitization (Baumann et al, 1991; LaMotte et al, 1991; Simone et al, 1991), defined by the International Association for the Study of Pain (IASP) as “increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input.”

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