Human brain responses to concomitant stimulation of Aδ and C nociceptors

Intense radiant heat pulses concomitantly activate Aδ- and C-fiber skin nociceptors, and elicit a typical double sensation: an initial Aδ-related pricking pain is followed by a C-related prolonged burning sensation. It has been repeatedly reported that C-fiber laser-evoked potentials (C-LEPs) become detectable only when the concomitant activation of Aδ-fibers is avoided or reduced. Given that the saliency of the eliciting stimulus is a major determinant of LEPs, one explanation for these observations is that the saliency of the C-input is smaller than that of the preceding Aδ-input. However, even if the saliency of the C-input is reduced because of the preceding Aδ-input, a C-LEP should still be visible even when preceded by an Aδ-LEP response. Here we tested this hypothesis by applying advanced signal processing techniques (peak alignment and time-frequency decomposition) to electroencephalographic data collected in two experiments conducted in 34 and 96 healthy participants. We show that, when using optimal stimulus parameters (delivering >80 stimuli within a small skin territory), C-LEPs can be reliably detected in most participants. Importantly, C-LEPs are observed even when preceded by Aδ-LEPs, both in average waveforms and single trials. By providing quantitative information about several response properties of C-LEPs (latency jitter, stimulus-response and perception-response functions, dependency on stimulus repetitions and stimulated area), these results define optimal parameters to record C-LEPs simply and reliably. These findings have important clinical implications for assessing small-fiber function in neuropathies and neuropathic pain.