Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: behavioral evidence

Behavioral nociceptive responses evoked by relatively high rates of noxious radiant skin heating appear to be mediated by A delta nociceptor activation, whereas responses evoked by low rates of skin heating appear to be mediated by the activation of C-fiber nociceptors. This hypothesis was confirmed by the results of single unit recordings of A delta and C nociceptive afferent fibers isolated from the saphenous nerves of pentobarbital anesthetized rats. Heating the hind paw skin of the rat at a relatively high rate of 6.5 degrees C/sec activated A delta units within 2 sec after the onset of the stimulus. This response latency is similar to the 2.5 sec latency of the foot withdrawal response to a similar stimulus. In contrast, C-fibers were only slightly activated at a longer latency of 5-6 sec. Conversely, heating the hind paw skin at a relatively low rate of 0.9 degrees C/sec activated C-fibers, but evoked only a few action potentials in A delta nociceptors. C-fibers began firing at a rate less than 1 Hz between 8 and 10 sec after the onset of heating and fired at a mean rate of 1.5 Hz between 10 and 12 sec, which corresponds to the latency of the foot withdrawal response. Topical application of capsaicin to the hind paw skin decreased the latency of C-fiber responses from control values of 8-12 sec to approximately 4 sec after topical capsaicin treatment. The mean latency of the foot withdrawal response to skin heating at the low rate is also reduced from control values of 12-14 sec to 4-5 sec after capsaicin treatment. In contrast, capsaicin treatment did not significantly affect the responses of A delta nociceptors. These results support the conclusion that nociceptive foot withdrawal responses to a low rate of skin heating are mediated predominantly by the activation of C-fiber nociceptors. These results provide direct evidence that, under the conditions of these experiments, nociceptive foot withdrawal responses evoked by high rates of skin heating are primarily mediated by A delta nociceptors, and foot withdrawal responses evoked by low rates of skin heating are primarily mediated by C-fiber nociceptors.