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

Abstract

Several lines of evidence suggest that different classes of nociceptive afferents mediate the responses produced by different rates of noxious skin heating. More specifically, low skin heating rates evoke nociceptive responses that appear to be mediated by the activation of capsaicin-sensitive C-fiber nociceptors, whereas high skin heating rates appear to produce responses mediated by the activation of other nociceptors. This hypothesis was examined by both electrophysiological and behavioral experiments. This report describes the results of experiments designed to determine whether pharmacologic treatments that selectively alter the activity of C-fiber nociceptive afferents also produce selective effects on foot withdrawal responses to either high or low rates of noxious foot heating. The results of these experiments demonstrate that: (1) topical application of a low concentration of capsaicin, which sensitizes C-fiber nociceptors, selectively decreased the latency of responses to low heating rates; (2) topical application of a high concentration of capsaicin, that desensitizes C-fiber nociceptors, selectively increased the latency of responses to low heating rates; (3) low doses of systemic morphine, which selectively attenuate nociception produced by the activation of C-fiber nociceptors, selectively increased response latencies for low skin heating rates. These results support the conclusion that foot withdrawal responses evoked by low skin heating rates are mediated by the activation of capsaicin-sensitive C-fiber nociceptors and foot withdrawal responses evoked by high skin heating rates are mediated by the activation of other nociceptors. This conclusion is supported by the results of the accompanying electrophysiological study which provides direct evidence that low rates of skin heating preferentially activate C-fiber nociceptors while high rates of skin heating preferentially activate A delta nociceptors.

Noxious Stimuli Evoke a Biphasic Flexor Reflex Composed of Aδ-Fiber-Mediated Short-Latency and C-Fiber-Mediated Long-Latency Withdrawal Movements in Mice

“…Our results in anesthetized mice are inconsistent with those of previous studies demonstrating that systemically administered morphine exhibits a more potent reduction of C-fiber-mediated nociception in anesthetized rats (1) and of neuronal responses in the dorsal horn of spinalized cats (2) than for those mediated by Ad -fibers. The sensitivity to morphine of the C-fiber-mediated reflex depends on the preparation with or without supraspinal influences.…”

Vertex-recorded, rather than primary somatosensory cortex-recorded, somatosensory-evoked potentials signal unpleasantness of noxious stimuli in the rat

“…Both noxious and tactile responses can be found within the 10-30 ms latency range [5,13,31,33]. However, with -opiate receptor agonists like fentanyl modulating noxious, rather than tactile, processing [6,16,34,41,42], the Vx-SEP and SI-SEP in the present study can be considered to represent processing of noxious stimuli. Secondly, fentanyl dose-dependently decreased the CS-induced fear-response as measured during the test sessions.…”

Dopamine D3Receptor Specifically Modulates Motor and Sensory Symptoms in Iron-Deficient Mice

“…The hotplate test was used to investigate differences in acute pain response to a thermal stimulus. The A␦ high-threshold heat nociceptors activate under high thermal stimulation and mediate fast reflex responses through a greater conduction velocity compared to C-fibers (Leem et al, 1993;Yeomans et al, 1996). Moreover, action potentials via A␦ fibers reach the spinal cord before those conducted by C-fiber nociceptors, corresponding to the recorded initial reflex to the noxious heat stimulus (Leem et al, 1993;Yeomans et al, 1996).…”

“…The A␦ high-threshold heat nociceptors activate under high thermal stimulation and mediate fast reflex responses through a greater conduction velocity compared to C-fibers (Leem et al, 1993;Yeomans et al, 1996). Moreover, action potentials via A␦ fibers reach the spinal cord before those conducted by C-fiber nociceptors, corresponding to the recorded initial reflex to the noxious heat stimulus (Leem et al, 1993;Yeomans et al, 1996). A high temperature, as used in our study, results in preferential A␦-fiber activation, whereby temperatures below a 45°C heat stimulation tend to involve a higher C-fiber activity (Adriaensen et al, 1983).…”