RESPONSES OF CUTANEOUS A-FIBER NOCICEPTORS TO NOXIOUS COLD

Responses of cutaneous nociceptors to natural stimuli, particularly me chanical and heat stimuli, have been well documented. Although nocicep tors are excited by noxious cold stimuli, there have been few studies of their stimulus-response functions for cold stimuli over a wide rang e of stimulus temperatures. Furthermore, the proportion of nociceptors excited by noxious cold is not clear. In the present study, we examin ed responses of mechanosensitive AS-nociceptors and low-threshold mech anoreceptors to a wide range of cold stimuli that included stimulus te mperatures <0 degrees C. Electrophysiological recordings were made fro m single primary afferent fibers in the saphenous nerves of anesthetiz ed rats. Cutaneous sensory receptors were classed according to their c onduction velocity and subgrouped functionally according to their resp onses evoked by mechanical, heat, and cold stimuli (0 degrees C). Resp onses evoked by a wide range of cold stimulus intensities that include d stimuli considered innocuous and noxious (painful) were then assesse d. Stimuli of 20 to -20 degrees C were delivered to the receptive fiel d via a l-cm contact thermode from a base temperature of 32 degrees C. Stimuli were applied in descending order of 2 degrees C decrements. S timulus ramp rate was 5 degrees C/s, and stimulus temperatures were ap plied for a duration of 10 s. A total of 90 A fibers was studied, of w hich 61 were nociceptors Md had conduction velocity in the A delta-ran ge (2-30 m/s). Nociceptors were classed initially as mechanical, mecha nobeat, and mechanocold nociceptors. The remaining 29 fibers were low- threshold mechanoreceptors with conduction velocity in the A delta- or A beta-range (>30 m/s). These were subgrouped according to their adap tive properties as slowly or rapidly adapting, and according to whethe r they were excited by hair movement (hair follicle afferent fibers). All nociceptors were excited by noxious cold. Only 30% of nociceptors were considered sensitive to cold on initial classification with the u se of a cold stimulus of O degrees C. However, all nociceptors were ex cited by stimulus intensities <O degrees C. Response thresholds for co ld ranged from 14 to - 18 degrees C (-4.6 +/- 1.07 degrees C, mean +/- SE). The total number of impulses, discharge rate, and peak discharge increased monotonically as intensity of cold stimuli increased. Power functions were used to determine the rate at which the number of impu lses increased as stimulus intensity increased. The slopes of power fu nctions ranged from 0.12 to 2.28 (mean 1.07 +/- 0.13). Most mechanorec eptors were not excited by cold stimuli. The only types of mechanorece ptors that responded reliably to cold stimuli were the slowly adapting mechanoreceptors. Responses usually occurred during the temperature r amp when the skin temperature was decreasing. There was no evidence th at mechanoreceptors encoded the intensity of cold stimuli at intensiti es above or below O degrees C, because evoked responses did not increa se with intensity of cold stimuli. It is concluded that the proportion of cutaneous AS-nociceptors excited by noxious cold stimuli has been underestimated in previous studies. All nociceptors were excited by st imulus temperatures <O degrees C and encoded the intensity of cold sti muli. It is therefore likely that cutaneous A delta-nociceptors contri bute to the sensation of cold pain, particularly pain produced by stim ulus temperatures <O degrees C.