C-polymodal nociceptors activated by noxious low temperature in human skin.

1. Fifty-five C-polymodal nociceptors innervating hairy skin in human volunteers were tested for discrete stimulus-response properties through microneurography. 2. All fifty-five units were responsive to mechanical and heat stimuli. Twenty-two (40%) of these exhibited an additional response to noxious low temperature. The twenty-two mechano-heat-cold nociceptors displayed similar receptor responses to heat and mechanical stimuli, and conduction velocity, as those of the pure mechano-heat C-polymodal nociceptors. 3. Low temperature stimuli between 19 and 0 degree C evoked responses at low discharge frequency (0.4 +/- 0.22 impulses s-1, mean +/- S.E.M.) in the twenty-two units sensitive to such energy. These units displayed a tendency to decrease their discharge after a few seconds of steady stimulation. 4. Three units tested with a freezing stimulus responded with relatively vigorous discharge, which never exceeded the maximal discharge frequency elicited by either mechanical or heat stimuli. One of these units became sensitized to heat after the freezing challenge. 5. It is concluded that a subpopulation of C-polymodal nociceptors is sensitive to noxious low temperature and may thus contribute to the determination of cold pain. The same type of primary afferent is probably one mediator of the symptom cold hyperalgesia in peripheral nerve disease.