Previous studies have suggested a pivotal role of the insular cortex in nociception and pain perception. Using a double-cone coil designed for deep transcranial magnetic stimulation, our objective was to assess (1) whether continuous theta burst stimulation (cTBS) of the operculo-insular cortex affects differentially the perception of different types of thermal and mechanical somatosensory inputs, (2) whether the induced after-effects are lateralized relative to the stimulated hemisphere, and (3) whether the after-effects are due to neuromodulation of the insula or neuromodulation of the more superficial opercular cortex. Seventeen participants took part in two experiments. In Experiment 1, thresholds and perceived intensity of Aδ- and C-fibre heat pain elicited by laser stimulation, non-painful cool sensations elicited by contact cold stimulation and mechanical vibrotactile sensations were assessed at the left hand before, immediately after and 20 min after deep cTBS delivered over the right operculo-insular cortex. In Experiment 2, Aδ-fibre heat pain and vibrotactile sensations elicited by stimulating the contralateral and ipsilateral hands were evaluated before and after deep cTBS or superficial cTBS delivered using a flat figure-of-eight coil. Only the threshold to detect Aδ-fibre heat pain was significantly increased 20 min after deep cTBS. This effect was present at both hands. No effect was observed after superficial cTBS. Neuromodulation of the operculo-insular cortex using deep cTBS induces a bilateral reduction of the ability to perceive Aδ-fibre heat pain, without concomitantly affecting the ability to perceive innocuous warm, cold or vibrotactile sensations.

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.

Secondary hyperalgesia refers to the increase in sensitivity to mechanical nociceptive stimuli delivered outside the area of tissue injury. Previous studies have suggested that secondary hyperalgesia is mediated by a specific class of myelinated nociceptors: slowly adapting A-fibre mechano- and heat-sensitive (AMH) type I nociceptors. Here, we tested this hypothesis by examining whether long-lasting heat stimuli, which are known to activate AMH-type I nociceptors, elicit enhanced responses when delivered to the area of secondary hyperalgesia induced by high frequency electrical stimulation of the skin (HFS). Before and 20 min after HFS, sustained 30 s radiant heat stimuli were delivered to the area of increased mechanical pinprick sensitivity while participants continuously rated intensity of perception using an online visual analog scale (0-100 mm). After HFS, no significant enhancement of heat perception was observed in the area of increased pinprick sensitivity. To establish that myelinated nociceptors actually contribute to the perception of sustained heat, we conducted a second experiment in which sustained heat stimuli were presented before and during an A-fibre nerve conduction block, achieved by applying a rubber band with weights which compresses the superficial radial nerve against the radius. During the block, heat perception was significantly reduced 17-33 s after the onset of the heat stimulus (before: mean = 53 mm, during: mean = 31 mm; P = 0.03), matching the response profile of AMH-type I nociceptors. These results support the notion that AMH-type I nociceptors contribute to the perception of sustained heat, but also show that these afferents do not mediate secondary hyperalgesia.

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. 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.

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