EEG frequency tagging using ultra-slow periodic heat stimulation of the skin reveals cortical activity specifically related to C fiber thermonociceptors

Abstract The recording of event‐related brain potentials triggered by a transient heat stimulus is used extensively to study nociception and diagnose lesions or dysfunctions of the nociceptive system in humans. However, these responses are related exclusively to the activation of a specific subclass of nociceptive afferents: quickly‐adapting thermonociceptors. In fact, except if the activation of A&dgr; fibers is avoided or if A fibers are blocked, these responses specifically reflect activity triggered by the activation of Type 2 quickly‐adapting A fiber mechano‐heat nociceptors (AMH‐2). Here, we propose a novel method to isolate, in the human electroencephalogram (EEG), cortical activity related to the sustained periodic activation of heat‐sensitive thermonociceptors, using very slow (0.2 Hz) and long‐lasting (75 s) sinusoidal heat stimulation of the skin between baseline and 50 °C. In a first experiment, we show that when such long‐lasting thermal stimuli are applied to the hand dorsum of healthy volunteers, the slow rises and decreases of skin temperature elicit a consistent periodic EEG response at 0.2 Hz and its harmonics, as well as a periodic modulation of the magnitude of theta, alpha and beta band EEG oscillations. In a second experiment, we demonstrate using an A fiber block that these EEG responses are predominantly conveyed by unmyelinated C fiber nociceptors. The proposed approach constitutes a novel mean to study C fiber function in humans, and to explore the cortical processing of tonic heat pain in physiological and pathological conditions.