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: Detailed characterization of neural circuitries furthers our understanding of how nervous systems perform specific functions and enables the use of those systems to test hypotheses. We have characterized the sensory input to the cutaneous trunk muscle (CTM; also cutaneus trunci (rat) or cutaneus maximus (mouse)) reflex (CTMR), which manifests as a puckering of the dorsal thoracolumbar skin and is selectively driven by noxious stimuli. CTM electromyography (EMG) and neurogram recordings in naïve rats revealed that CTMR responses were elicited by natural stimuli and electrical stimulation of all segments from C4 to L6, a much greater extent of segmental drive to the CTMR than previously described. Stimulation of some subcutaneous paraspinal tissue can also elicit this reflex. Using a selective neurotoxin, we also demonstrate differential drive of the CTMR by trkA-expressing and non-expressing small diameter afferents. These observations highlight aspects of the organization of the CTMR system which make it attractive for studies of nociception and anesthesiology and plasticity of primary afferents, motoneurons, and the propriospinal system. We use the CTMR system to qualitatively and quantitatively demonstrate that experimental pharmacological treatments can be compared to controls applied either to the contralateral side or to another segment, with the remaining segments providing controls for systemic or other treatment effects. These data indicate the potential for using the CTMR system as both an invasive and non-invasive quantitative assessment tool providing improved statistical power and reduced animal use. J. Comp. Neurol., 2013. © 2013 Wiley Periodicals, Inc.The Journal of Comparative Neurology 08/2013; · 3.66 Impact Factor
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ABSTRACT: This study describes a modified Hargreaves' method for assessing paw withdrawal threshold temperatures for heat (PWT-H) nociception in the rat hind paws. The method utilizes applications of radiant heat to maintain controlled lamp temperatures (CLT) on a glass floor beneath the rat hind paw. An ascending series of CLTs were each applied for 10-s, with 5-10min intervals between applications, until a characteristic withdrawal behavior was observed, or a cutoff CLT was reached. Average plantar epicutaneous temperatures measured from anesthetized rats corresponding to CLTs and withdrawal latencies were used for determining PWT-H. The mean PWT-H in 2-months old (mo) naïve Sprague-Dawley rats (n=38) was 47.6±0.2˚C, and is comparable to the noxious threshold temperature for human glabrous skin (46.5±0.5˚C). The PWT-H is consistent between trials and daily assessments over four consecutive days. No significant differences were observed between the PWT-H in 2 mo, 6-8 mo, and >24 mo F344 rats, but the PWT-H in 1-mo rats was significantly decreased. Three hours following plantar incision, the PWT-H decreased to 37.5±0.2°C, which correlates with previous observations of C-fiber afferents from incised glabrous skin firing at 36.7±3.6°C. Parallel testing with the current method and an electronic von Frey device illustrated similar degrees of incision-induced hyperalgesia, improvement of hyperalgesia over time, and reversals induced by morphine and gabapentin. In conclusion, the present method allows us to compare PWT-H with electrophysiological and human psychophysical studies involving thermosensation and, as a behavioral assay identical to von Frey testing in measuring threshold for nociception.Journal of neuroscience methods 06/2013; · 2.30 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