Recordings of polymodal single c-fiber nociceptive afferents following mechanical and argon-laser heat stimulation of human skin

Abstract

Recordings were made in the peroneal nerve of healthy volunteer subjects from C-mechano-heat (CMH) nociceptors (n=25) with their receptive fields in the skin on the dorsum of the foot. The investigation focused on afferent single C-fiber activity induced by short (200 ms) high-intensity argon-laser light pulses projected to localized spots of the skin. Cutaneous heat stimulation with the argon laser, 2-3 times the activation threshold, induced inter-burst spike frequencies in the nerve, reaching 50 Hz, while mechanical stimulation 10-20 times threshold only evoked frequencies reaching 10 Hz. The decrease in conduction velocity of action potentials in the C-fiber afferents following mechanical and heat stimulation was closely related to the degree of activation. Following a laser pulse of 200 ms, a spike pattern with highly reproducible inter-spike intervals was evoked with a fast saturation. On the contrary, a high variability in the number of action potentials evoked by both heat and mechanical stimuli was found, depending on the location of stimuli within the receptive field. A relation between the conduction velocity and the peak firing within the spike train following laser stimulation was detected. Heat and mechanical stimulation activated single C-fibers in matching spots within the same skin areas, in line with the assumption that the two modalities in the CMH-fibers share matching morphological cutaneous substrates. No correlation was found in thresholds or excitability to mechanical and heat stimulation, respectively. This suggests that subsets of receptors exist within nerve endings of the cutaneous receptive fields, with the ability to generate action potentials independent of heat and mechanical stimuli. Unexpectedly, no signs of sensitization or other inflammatory responses were observed after repeated laser pulses; on the contrary, a rapidly developing fatigue was observed when single spots were repeatedly stimulated. However, no fatigue was observed if neighboring spots were stimulated, indicating a localized generator of the fatigue. In each subject, a good correlation was observed between the reported pain sensation and the activity evoked in the afferent C-fibers by the laser. However, the magnitude of the reported pain sensation to comparable degrees of C-fiber activation showed a high variability between different subjects. A fairly good subjective estimate of the afferent-fiber activation was observed when skin spots from 3- down to 1-mm diameter were stimulated. In a few individuals, no painful sensation was reported when the stimulated spots were reduced to 1-mm diameter, despite the occurrence of multiple spikes in single C-fiber afferents, amplifying the importance of spatial summation in the perception of pain.