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.
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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). "
ABSTRACT: Neural mechanisms underlying nociception and pain perception are considered to serve the ultimate goal of limiting tissue damage. However, since pain usually occurs in complex environments and situations that call for elaborate control over behavior, simple avoidance is insufficient to explain a range of mammalian pain responses, especially in the presence of competing goals. In this integrative review we propose a Predictive Regulation and Action (PRA) model of acute pain processing. It emphasizes evidence that the nervous system is organized to anticipate potential pain and to adjust behavior before the risk of tissue damage becomes critical. Regulatory processes occur on many levels, and can be dynamically influenced by local interactions or by modulation from other brain areas in the network. The PRA model centers on neural substrates supporting the predictive nature of pain processing, as well as on finely-calibrated yet versatile regulatory processes that ultimately affect behavior. We outline several operational categories of pain behavior, from spinally-mediated reflexes to adaptive voluntary action, situated at various neural levels. An implication is that neural processes that track potential tissue damage in terms of behavioral consequences are an integral part of pain perception.Frontiers in Human Neuroscience 11/2013; 7:755. DOI:10.3389/fnhum.2013.00755
- "Selective activation of Ad-fibers was accomplished by using a diode laser with a high rate heating, high energy, brief pulses, and small spot sizes. Selective activation of C-fibers was accomplished by low rate heating with long pulses, low energy and larger spot sizes    . The diode laser has been previously used to selectively activate transient receptor potential vanilloid (TRPV1 and TRPV2) positive cells , to selectively activate C-and Ad-fibers in rats , to elicit a heat-activated inward current I heat in dorsal root ganglion neurons of rats in vitro, and to elicit laser-evoked potentials (LEPs) associated with activation of Ad-and C-nociceptors in humans  . "
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- "Mild analgesics, as aspirin, lack antinociceptive action in thermally motivated tests such as hot plate test, but have significant antinociceptive activity in tonic tests (writhing and formalin tests), which are characterized by the direct chemical stimulation of nociceptors. Since, it has been reported that thermally motivated and tonic tests elicit the selective stimulation of A-γ fibers and C fibers, respectively (Yeomans et al.,1996), it is tempting to propose that PRAE may interfere with the transmission of both fibers or a common pathway. "
ABSTRACT: The present work investigated the antinociceptive and antiinflammatory activities of the Porophyllum ruderale (Jacq.) Cass., Asteraceae, aqueous extract (PRAE). For this purpose, acetic acid writhing, paw licking induced by formalin, hot-plate and pleurisy tests were performed. The doses of 100, 200 and 400 mg/kg (p.o.) significantly inhibited the writhing 63.4, 89.6 and 94.8%, respectively, in comparison with control group. The lick of the paw 1st phase was reduced at the dose of 400 mg/ kg (24.9%), while the 2nd phase had reduction at doses 200 and 400 mg/ kg (23.1 and 34.4%), respectively. The PRAE inhibited the carrageenaninduced neutrophil migration to the peritoneal cavity in a higher dose (p<0.05). Taken together, our results suggest that the PRAE can constitute target potential for use in therapies of the pain and inflammation.Revista Brasileira de Farmacognosia 06/2011; 21(3):486-490. DOI:10.1590/S0102-695X2011005000051