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

Department of Pharmacology, University of Illinois at Chicago, 60612, USA.
Pain (Impact Factor: 5.21). 12/1996; 68(1):133-40. DOI: 10.1016/S0304-3959(96)03176-4
Source: PubMed


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.

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    • "Two days after CFA injection, mice were lightly anesthetized with urethane (600 mg/kg ip) and placed with minimal restraint on a heating pad to maintain their body temperature at 37°C. It has been shown in previous studies32,33 that light urethane anesthesia (500–600 mg/kg) does not alter withdrawal latencies to noxious thermal stimuli. The laser beam was directed via the fiberoptic cable to the rostral external part of the left ear. "
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    • "The formalin test, which involves chemically injuring tissue by formalin injection, is another standard protocol for probing withdrawal and protective behaviors (Dubuisson and Dennis, 1977). Heat, cold, and mechanical stimuli elicit withdrawal or flexion reflexes in both awake (Chaplan et al., 1994; McMullan et al., 2004; Dunham et al., 2010) and anesthetized animals (Bessou et al., 1971; Yeomans et al., 1996). C heat fibers (including polymodal C fibers) and Aδ fibers underlie the initial encoding of a noxious heat stimulus (Dunham et al., 2010), and Aδ fibers also signal noxious skin deformations from mechanical stimuli (Bessou et al., 1971; Lewin and Moshourab, 2004). "
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