Novel approaches to tag cortical activity specific for nociception

Studies have shown that the repetition of a stimulus may induce, at certain frequencies of stimulation, a sustained electro-cortical response of corresponding frequency, referred to as steady-state evoked potentials (SS-EPs). Unlike event-related potentials (ERPs), which reflect phasic cortical activity triggered by a transient stimulus. SS-EPs reflect sustained cortical activity triggered by a wave of repetitive stimuli. In other sensory modalities, it has been shown that SS-EPs result from an entrainment of neuronal populations responding to the stimulus at the frequency of stimulation, originating mainly from early, sensory-specific cortices. Our objective was to explore and characterize, for the first time, SS-EPs elicited by the rapid periodic stimulation of cutaneous nociceptors. Two different approaches were used to generate the required periodic nociceptive input. The first relied on infrared CO2 laser stimulation of heat-sensitive skin nociceptors (see Figure). The second relied on direct intra-epidermal electrical stimulation of nociceptive free nerve endings using a needle cathode surrounded by a cylindrical anode. Consistent nociceptive and non-nociceptive SSEPs were recorded using a wide range of stimulation frequencies (3-43 Hz). The magnitude, scalp topography and temporal dynamics of the obtained responses were compared to the SS-EPs elicited by non-nociceptive vibrotactile stimulation (Figure 2). Whereas non-nociceptive SSEPs were maximal over the parietal region contralateral to the stimulated side, nociceptive SSEPs were maximal at the vertex and symmetrically distributed over both hemispheres, thus indicating that nociceptive and non-nociceptive SS-EPs reflect the entrainment of distinct neuronal populations. Furthermore, the responses did not habituate over time, suggesting that they reflect obligatory stages of sensory processing. Taken together, the results of this project indicate that the recording of nociceptive SS-EPs could constitute a novel and promising mean to study the cortical processes involved in nociception and the perception of pain.