Preceding events condition the central processing of nociceptive input as revealed by laser-evoked potentials

A. Mouraux, Laboratoire de Neurophysiologie (NEFY), Université Catholique de Louvain

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Summary

Pain, defined as a percept, is a complex and primarily subjective experience which involves multidimensional sensory, motivational, and cognitive components. The sensory system producing this perception, sometimes referred to as the ‘nociceptive’ system, consists in cutaneous and visceral nociceptors (present in all tissues except the brain), peripheral A [delta]- and C-fiber afferent fibers, and spinal transmission neurons which modulate and project this peripheral input to supraspinal structures such as the brain stem, the thalamus, the limbic system, and the cortex. By selectively and synchronously activating A[delta]- and C-fiber nociceptors, laser heat stimulators have been extensively used to study electrical brain responses involved in nociception. Concomitant activation of A[delta]- and C-fibers produces a dual sensation, composed of first and second pain, but evokes only a single, A[delta]-fiber related, late laser-evoked potential (LEP). Yet, when concomitant activation of A[delta]-fibers is avoided, a C-fiber related ultra-late LEP response is recorded. This well known but poorly understood phenomenon should be taken into account when one infers on the functional significance of the processes these responses reflect. Indeed, the apparent dissociation between perceptual and electrophysiological correlates of A[delta]- and C-nociceptor activation suggests that LEPs reflect cortical processes which are not required for the perception of first or second pain.

Study 1. In addition to evoked-potentials, sensory, motor, and cognitive events may induce transient enhancements or attenuations of ongoing EEG oscillations. Hypotheses are that these modulations reflect mechanisms involved in cortical activation, inhibition, and probably binding. However, these electrophysiological responses are cancelled-out by conventional time-averaging procedures. In a first study, novel time-frequency signal-processing methods were developed and applied to the analysis of laser-induced EEG changes. Use of these methods showed that LEPs constitute only a fraction of the EEG response. Several time-locked but non-stationary EEG responses were identified.

Study 2. The most commonly accepted hypothesis to explain why a preceding A [delta]-fiber afferent volley appears to occlude later-arriving C-fiber LEP responses relies on the assumption that both responses reflect the activation of shared cortical generators which would be subject to ‘refractoriness’. This hypothesis was examined in a second study using two consecutive laser pulses applied with variable inter-stimulus intervals.

Study 3. It was also proposed that a necessary condition for C-fiber inputs to elicit ultra-late LEP responses would be that attention be entirely focused on that specific sensory channel. This hypothesis was examined in a third study where subjects were trained to selectively attend to the C-fiber mediated sensation of second pain.

Taken together, results of these three studies indicate that LEPs reflect very general processes constituting only a fraction of the central processing of nociceptive input and mainly related to detection and attentional orientation.