Cédric Lenoir

Secondary hyperalgesia is mediated by heat‐insensitive A‐fibre nociceptors

It is believed that secondary hyperalgesia (the increased sensitivity to mechanical nociceptive stimuli that develops after cutaneous tissue injury in the surrounding uninjured skin) is mediated by a subclass of nociceptors: the slowly adapting A‐fibre mechano‐heat nociceptors (AMH‐type I). Here we tested this hypothesis. By using intense long‐lasting heat stimuli, which are known to activate these slowly adapting AMH‐type I nociceptors, we show that the perceived intensity elicited by these stimuli is not increased in the area of secondary hyperalgesia. Moreover, we show that during an A‐fibre nerve conduction block the perception elicited by the long‐lasting heat stimuli is significantly reduced in a time window that matches the response profile of the AMH‐type I nociceptors. AMH‐type I nociceptors contribute to the perception of sustained heat, but they do not mediate secondary hyperalgesia. Therefore, we propose that secondary hyperalgesia is mediated by high threshold mechanoreceptors.

Human primary somatosensory cortex is differentially involved in vibrotaction and nociception

The role of the primary somatosensory cortex (S1) in vibrotaction is well established. In contrast, its involvement in nociception is still debated. Here we test whether S1 is similarly involved in the processing of nonnociceptive and nociceptive somatosensory input in humans by comparing the aftereffects of high-definition transcranial direct current stimulation (HD-tDCS) of S1 on the event-related potentials (ERPs) elicited by nonnociceptive and nociceptive somatosensory stimuli delivered to the ipsilateral and contralateral hands. Cathodal HD-tDCS significantly affected the responses to nonnociceptive somatosensory stimuli delivered to the contralateral hand: both early-latency ERPs from within S1 (N20 wave elicited by transcutaneous electrical stimulation of median nerve) and late-latency ERPs elicited outside S1 (N120 wave elicited by short-lasting mechanical vibrations delivered to index fingertip, thought to originate from bilateral operculo-insular and cingulate cortices). These results support the notion that S1 constitutes an obligatory relay for the cortical processing of nonnociceptive tactile input originating from the contralateral hemibody. Contrasting with this asymmetric effect of HD-tDCS on the responses to nonnociceptive somatosensory input, HD-tDCS over the sensorimotor cortex led to a bilateral and symmetric reduction of the magnitude of the N240 wave of nociceptive laser-evoked potentials elicited by stimulation of the hand dorsum. Taken together, our results demonstrate in humans a differential involvement of S1 in vibrotaction and nociception.NEW & NOTEWORTHY Whereas the role of the primary somatosensory cortex (S1) in vibrotaction is well established, its involvement in nociception remains strongly debated. By assessing, in healthy volunteers, the effect of high-definition transcranial direct current stimulation over S1, we demonstrate a differential involvement of S1 in vibrotaction and nociception.

Quickly responding C‐fibre nociceptors contribute to heat hypersensitivity in the area of secondary hyperalgesia

A recent animal study showed that high frequency electrical stimulation (HFS) of C‐fibres induces a gliogenic heterosynaptic long‐term potentiation at the spinal cord that is hypothesized to mediate secondary hyperalgesia in humans. Here this hypothesis was tested by predominantly activating C‐fibre nociceptors in the area of secondary mechanical hyperalgesia induced by HFS in humans. It is shown that heat perception elicited by stimuli predominantly activating C‐fibre nociceptors is greater, as compared to the control site, after HFS in the area of secondary mechanical hyperalgesia. This is the first study that confirms in humans the involvement of C‐fibre nociceptors in the changes in heat sensitivity in the area of secondary mechanical hyperalgesia induced by HFS.

Deep continuous theta burst stimulation of the operculo‐insular cortex selectively affects Aδ‐fibre heat pain

Deep continuous theta burst stimulation (cTBS) of the right operculo‐insular cortex delivered with a double cone coil selectively impairs the ability to perceive thermonociceptive input conveyed by Aδ‐fibre thermonociceptors without concomitantly affecting the ability to perceive innocuous warm, cold or vibrotactile sensations. Unlike deep cTBS, superficial cTBS of the right operculum delivered with a figure‐of‐eight coil does not affect the ability to perceive thermonociceptive input conveyed by Aδ‐fibre thermonociceptors. The effect of deep operculo‐insular cTBS on the perception of Aδ‐fibre input was present at both the contralateral and the ipsilateral hand. The magnitude of the increase in Aδ‐heat detection threshold induced by the deep cTBS was significantly correlated with the intensity of the cTBS pulses. Deep cTBS delivered over the operculo‐insular cortex is associated with a risk of transcranial magnetic stimulation‐induced seizure.

Anodal Transcutaneous Spinal Direct Current Stimulation (tsDCS) Selectively Inhibits the Synaptic Efficacy of Nociceptive Transmission at Spinal Cord Level

Recently studies have aimed at developing transcutaneous spinal direct current stimulation (tsDCS) as a non-invasive technique to modulate spinal function in humans. Independent studies evaluating its after-effects on nociceptive or non-nociceptive somatosensory responses have reported comparable effects suggesting that tsDCS impairs axonal conduction of both the spino-thalamic and the medial lemniscus tracts. The present study aimed to better understand how tsDCS affects, in humans, the spinal transmission of nociceptive and non-nociceptive somatosensory inputs. We compared the after-effects of anodal low-thoracic, anodal cervical and sham tsDCS on the perception and brain responses elicited by laser stimuli selectively activating Aδ-thermonociceptors of the spinothalamic system and vibrotactile stimuli selectively activating low-threshold Aβ-mechanoreceptors of the lemniscal system, delivered to the hands and feet. Low-thoracic tsDCS selectively and significantly affected the LEP-N2 wave elicited by nociceptive stimulation of the lower limbs, without affecting the LEP-N2 wave elicited by nociceptive stimulation of the upper limbs, and without affecting the SEP-N2 wave elicited by vibrotactile stimulation of either limb. This selective and segmental effect indicates that the neuromodulatory after-effects of tsDCS cannot be explained by anodal blockade of axonal conduction and, instead, are most probably due to a segmental effect on the synaptic efficacy of the local processing and/or transmission of nociceptive inputs in the dorsal horn.