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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ABSTRACT: RATIONALE: Isolation rearing in rodents causes not only abnormal behaviors which resemble the clinical symptoms of schizophrenia but also hypoalgesia in thermal nociception models. However, the mechanism of the hypoalgesia is not known. OBJECTIVES: The present study investigated the effect of isolation rearing on acute pain and the descending pain inhibitory pathways in mice. RESULTS: Rearing in isolation for 6 weeks from post-weaning reduced pain sensitivity in the hot plate test and acetic acid-induced writhing test. Isolation rearing also reduced the intraplantar capsaicin-induced licking behavior. Capsaicin increased c-Fos expression, a neuronal activity marker, in the spinal cord and primary somatosensory cortex both in group- and isolation-reared mice, but this effect did not differ between groups. On the other hand, c-Fos expression in the anterior cingulate cortex, periaqueductal gray matter, and rostral ventromedial medulla, but not in the spinal cord or somatosensory cortex, was enhanced by isolation rearing. Systemic administration of WAY100635 (serotonin (5-HT)(1A) receptor antagonist), but not of ketanserin (5-HT(2) receptor antagonist), prazosin (α(1)-adrenoceptor antagonist), or yohimbine (α(2)-adrenoceptor antagonist), attenuated isolation rearing-induced hypoalgesia in capsaicin-induced licking behavior. Attenuation of isolation rearing-induced hypoalgesia was also observed following the intrathecal injection of WAY100635. Naloxone, an opioid receptor antagonist, did not affect the hypoalgesia in isolation-reared mice. CONCLUSIONS: These findings suggest that isolation rearing causes hypoalgesia in mouse models of acute pain and imply that the spinal 5-HT(1A) receptor activation probably through descending serotonergic inhibitory pathway is involved in isolation rearing-induced hypoalgesia.Psychopharmacology 12/2012; · 4.06 Impact Factor
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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 herpes simplex virus type 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 naive 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 adjuvant 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 advance online publication, 27 February 2014; doi:10.1038/gt.2014.14.Gene therapy 02/2014; · 4.75 Impact Factor