Antinociception induced by local injections of carbachol into the nucleus raphe magnus in rats: Alteration by intrathecal injection of monoaminergic antagonists |
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| Authors: | Mark S. Brodie Herbert K. Proudfit |
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| Affiliation: | 1. Department of Pharmacy – Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany;2. Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine Universität Düsseldorf, Düsseldorf, Germany;3. Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany;4. Institute of Bio, and Geosciences (IBG-4: Bioinformatics), Forschungszentrum Jülich, Jülich, Germany;1. Key Laboratory of Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;3. State Key Lab of Urban Water Resource and Environment, School of Civil and Environmental Engineering, Harbin Institute of Technology Shenzhen, Shenzhen 518055, China;4. College of Civil Engineering, Nanjing Tech University, Nanjing 211816, China;5. Key Laboratory of Coastal Environment and Resources of Zhejiang Province, School of Engineering, Westlake University, Hangzhou, Zhejiang 310030, China;1. Institute of Agricultural Science in the Tropics (Hans-Ruthenberg Institute), University of Hohenheim, 70593 Stuttgart, Germany;2. Africa Rice Center, c/o FOFIFA Tsivatrinikamo, Ambaniandrefana. B.P. 230, Antsirabe 110, Madagascar;3. World Agroforestry Centre (ICRAF), China & East Asia Office c.o. Kunming Institute of Botany CAS, Kunming 65021, China;4. Key laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany CAS, Kunming 65021, China;1. Department of Applied Chemistry, University of Sistan and Baluchestan, P.O. Box 98135-674, Zahedan, Iran;2. Department of Chemistry, Organic and Polymer Research Laboratory, University of Sistan and Baluchestan, Zahedan, Iran;3. Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada |
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| Abstract: | Electrical stimulation of neurons located in the nucleus raphe magnus (NRM) produces antinociception which appears to result from inhibition of spinothalamic tract neurons located in the spinal cord dorsal horn. Iontophoretic application of acetylcholine also activates NRM neurons and microinjection of cholinergic agonists such as carbachol into the NRM produces a profound, long-lasting antinociception. Since the antinociception induced by electrical stimulation of NRM neurons is mediated, at least in part, by bulbospinal serotonergic and noradrenergic neurons, the role of these monoaminergic neurons in mediating the antinociception induced by microinjecting carbachol in the NRM was examined in the present study. To this end, various antagonists of serotonin and norepinephrine were injected into the spinal cord subarachnoid space following the induction of antinociception by the local injection of carbachol into the NRM. The serotonergic antagonist methysergide had no effect on carbachol-induced antinociception. However, the alpha 2-noradrenergic antagonist yohimbine attenuated, while the alpha 1-noradrenergic antagonists prazosin and WB4101 increased the effects of carbachol. The non-selective noradrenergic antagonist phentolamine also attenuated the effects of carbachol. These results lead to the suggestion that the antinociception induced by the local injection of carbachol into the NRM is mediated by selective activation of bulbospinal noradrenergic neurons. Furthermore, the antinociception resulting from the activation of these descending noradrenergic neurons appears to be mediated by alpha 2-noradrenergic receptors located in the spinal cord dorsal horn. Finally, the local injection of carbachol into the NRM also appears to activate another population of noradrenergic neurons which produces hyperalgesia mediated by alpha 1-noradrenergic receptors. |
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| Keywords: | antinociception pain cholinergic neuron noradrenergic neuron nucleus raphe magnus spinal cord |
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