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

Abstract

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.

Prevention of sensory disorders in diabetic Sprague-Dawley rats by aldose reductase inhibition or treatment with ciliary neurotrophic factor

“…In our previous studies using adult female streptozotocin-diabetic rats, we have routinely found that thermal hypoalgesia develops in the hind paw after approximately 8 weeks [14,15,16,17] when using a system that selectively activates C fibres by increasing contact surface temperature from 30 to 50°C over a 20-second period [18]. Thermal hypoalgesia was prevented by treating rats with a neuroactive peptide that did not alter the general physiological condition of the animals [15,16], indicating that thermal hypoalgesia is unlikely to be a consequence of cachexia or altered thermal transduction properties of the skin.…”

Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain

“…From the present data we cannot conclude why IK 950 appeared more effective using mechanical stimulation, however, this difference could be explained by differences in the recruitment of primary afferent fiber types with thermal versus mechanical stimulation. While the slowly ramping heat stimulus selectively activates unmyelinated C fiber nociceptors (Yeomans and Proudfit, 1996), the von Frey filaments would have necessarily recruited both mechanosensitive Aδ and C nociceptors as well as low-threshold tactile Aβ fibers. Thus, the greater effect of IK 950 using mechanical compared to noxious thermal stimulation could have resulted from combined effects on multiple fiber types that culminated in a relatively greater reduction in primary afferent input converging on spinal nociceptive dorsal horn neurons.…”

Hypothalamic and Midbrain Circuitry That Distinguishes Between Escapable and Inescapable Pain

“…The potential significance of this issue led us to develop a noninvasive technique, as first described by Yeomans and colleagues (20), whereby we could reliably and reproducibly activate preferentially either C-or A/-nociceptors. Slow heating rates (2.5°C/s) applied to a hindpaw dorsum were used to activate capsaicin-sensitive heat nociceptors, and higher rates (7.5°C/s) of heating applied to the same cutaneous fields were used to activate a population of heat nociceptors that were capsaicin insensitive.…”