Development of secondary hyperalgesia following non-painful thermal stimulation of the skin: a psychophysical study in man

Abstract

A psychophysical study has been carried out in 10 normal human subjects to examine whether conscious perception of pain is necessary for the development of secondary hyperalgesia. Prolonged thermal stimulation of the skin was applied to the subjects at intensities known to evoke discharges in polymodal nociceptors but insufficient to evoke pain sensations. During this stimulation the development of punctate and of stroking hyperalgesia was examined as was the presence of a skin flare indicative of nociceptor activation. All subjects developed a flare and an area of hyperalgesia following the application of the non-painful heat stimulus. The first change observed in the subjects was the appearance of an area of hyperalgesia to punctate stimuli, followed by flare and by stroking hyperalgesia. The onset of pain was always reported sometime after these events. Statistical analysis of these data for all subjects showed a highly significant difference between the time of onset of pain and the time of onset of any of the other 3 phenomena. Significant differences were also observed between the onset of punctate hyperalgesia and the onsets of flare and of stroking hyperalgesia. No difference was observed between the onset of flare and of stroking hyperalgesia. These results show that cutaneous hyperalgesia can be evoked in normal human subjects by prolonged thermal stimulation of the skin at temperatures that are not perceived as painful. The development of a flare in all subjects simultaneously with stroking hyperalgesia but before the perception of pain suggests that activation of nociceptors is necessary for the hyperalgesia to occur. Since the perception of a pain sensation is not the triggering factor for the development of cutaneous hyperalgesia the CNS mechanisms responsible for secondary hyperalgesia must involve alterations of sensory processing at sub-cortical levels.