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
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.
Available from: David C Yeomans
- "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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ABSTRACT: The aim of this study was to test the efficacy of a single direct injection of viral vector encoding for encephalin to induce a widespread expression of the transgene and potential analgesic effect in trigeminal behavioral pain models in mice. After direct injection of HSV-1 based vectors encoding for human preproenkephalin (SHPE) or the lacZ reporter gene (SHZ.1, control virus) into the trigeminal ganglia in mice, we performed an orofacial formalin test and assessed the cumulative nociceptive behavior at different time points after injection of the viral vectors. We observed an analgesic effect on nociceptive behavior that lasted up to 8 weeks after a single injection of SHPE into the trigeminal ganglia. Control virus injected animals showed nociceptive behavior similar to naïve mice. The analgesic effect of SHPE injection was reversed/attenuated by subcutaneous naloxone injections, a μ-opioid receptor antagonist. SHPE injected mice also showed normalization in withdrawal latencies upon thermal noxious stimulation of inflamed ears after subdermal complete Freund’s adjuvans injection indicating widespread expression of the transgene. Quantitative immunohistochemistry of trigeminal ganglia showed expression of human preproenkephalin after SHPE injection.
Direct injection of viral vectors proved to be useful for exploring the distinct pathophysiology of the trigeminal system and could also be an interesting addition to the pain therapists’ armamentarium.
Gene therapy 02/2014; 21(4). DOI:10.1038/gt.2014.14 · 3.10 Impact Factor
Available from: Irene Perini
- "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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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 · 3.63 Impact Factor
Available from: Jens Schouenborg
- "To develop new analgesics, appropriate animal models of pain are crucial. The current models are based primarily on measuring changes in motor responses –. Because the nociceptive input to motor systems and to sensory systems are channelled through at least partly different central pathways, with different physiological and pharmacological properties –, the validity of motor responses in predicting sensory aspects of pain and analgesia is not always clear –. "
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ABSTRACT: CO(2)-laser C-fibre evoked cortical potentials (LCEPs) is a potentially useful animal model for studies of pain mechanisms. A potential confounding factor when assessing analgesic effects of systemically administered drugs using LCEP is sedation. This study aims to clarify: 1) the relation between level of anaesthesia and magnitude of LCEP, 2) the effects of a sedative and an analgesic on LCEP and dominant EEG frequency 3) the effects of a sedative and analgesic on LCEP when dominant EEG frequency is kept stable. LCEP and EEG were recorded in isoflurane/nitrous-oxide anaesthetized rats. Increasing isoflurane level gradually reduced LCEPs and lowered dominant EEG frequencies. Systemic midazolam (10 μmol/kg) profoundly reduced LCEP (19% of control) and lowered dominant EEG frequency. Similarly, morphine 1 and 3 mg/kg reduced LCEP (39%, 12% of control, respectively) and decreased EEG frequency. When keeping the dominant EEG frequency stable, midazolam caused no significant change of LCEP. Under these premises, morphine at 3 mg/kg, but not 1 mg/kg, caused a significant LCEP reduction (26% of control). In conclusion, the present data indicate that the sedative effects should be accounted for when assessing the analgesic effects of drug. Furthermore, it is suggested that LCEP, given that changes in EEG induced by sedation are compensated for, can provide information about the analgesic properties of systemically administrated drugs.
PLoS ONE 01/2013; 8(1):e53966. DOI:10.1371/journal.pone.0053966 · 3.23 Impact Factor
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