| Opioids disrupt pro-nociceptive modulation mediated by raphe magnus. | |
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MedLine Citation:
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PMID: 23035079 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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In anesthetized rats, opioid analgesia is accompanied by a specific pattern of tonic activity in two neuronal populations within the medullary raphe magnus (RM): opioids silence pain-facilitatory ON cells and produce sustained discharge in pain-inhibitory OFF cells. These tonic activity patterns, hypothesized to generate a tonic analgesic state, have not been observed in recordings made without anesthesia. Therefore, we recorded ON and OFF cell activity before and after an analgesic dose of morphine in unanesthetized mice. The tonic activity of ON and OFF cells was unchanged by morphine. Rather, morphine suppressed the phasic ON cell excitation and OFF cell inhibition evoked by noxious stimulation. Before morphine, the magnitude of the noxious stimulus-evoked burst in ON cells correlated with motor withdrawal magnitude, suggesting that ON cells facilitate nocifensive motor reactions. Contrary to model prediction, OFF cell activity was greater before stimulus trials that evoked withdrawals than those without withdrawals. Since withdrawals only occurred when OFF cell activity was suppressed, a decrease in OFF cell activity appears to serve as a pro-nociceptive signal that synchronizes and therefore strengthens the ensuing motor reaction. We further propose that morphine acts in RM to suppress ON and OFF cell phasic responses and thereby disable RM's pro-nociceptive output. Thus, RM cells produce antinociception by failing to exert the pro-nociceptive effects normally engaged by noxious stimulation. These findings revise the conventional understanding of supraspinal opioid analgesia and demonstrate that RM produces on demand rather than state modulation, allowing RM cells to serve other functions during pain-free periods. |
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Authors:
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Kevin M Hellman; Peggy Mason |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 32 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 13668-78 Citation Subset: IM |
Affiliation:
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Departments of Neurobiology, and Obstetrics and Gynecology, University of Chicago, Chicago, Illinois 60637, and NorthShore University HealthSystem, Evanston, Illinois 60201. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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