Source:http://linkedlifedata.com/resource/pubmed/id/15814796
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
14
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pubmed:dateCreated |
2005-4-7
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pubmed:abstractText |
Opioid mu- and delta-receptors are present on the central terminals of primary afferents, where they are thought to inhibit neurotransmitter release. This mechanism may mediate analgesia produced by spinal opiates; however, when they used neurokinin 1 receptor (NK1R) internalization as an indicator of substance P release, Trafton et al. (1999) noted that this evoked internalization was altered only modestly by morphine delivered intrathecally at spinal cord segment S1-S2. We reexamined this issue by studying the effect of opiates on NK1R internalization in spinal cord slices and in vivo. In slices, NK1R internalization evoked by dorsal root stimulation at C-fiber intensity was abolished by the mu agonist [D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO) (1 microM) and decreased by the delta agonist [D-Phe2,5]-enkephalin (DPDPE) (1 microM). In vivo, hindpaw compression induced NK1R internalization in ipsilateral laminas I-II. This evoked internalization was significantly reduced by morphine (60 nmol), DAMGO (1 nmol), and DPDPE (100 nmol), but not by the kappa agonist trans-(1S,2S)-3,4-dichloro-N-mathyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride (200 nmol), delivered at spinal cord segment L2 using intrathecal catheters. These doses of the mu and delta agonists were equi-analgesic as measured by a thermal escape test. Lower doses neither produced analgesia nor inhibited NK1R internalization. In contrast, morphine delivered by percutaneous injections at S1-S2 had only a modest effect on thermal escape, even at higher doses. Morphine decreased NK1R internalization after systemic delivery, but at a dose greater than that necessary to produce equivalent analgesia. All effects were reversed by naloxone. These results indicate that lumbar opiates inhibit noxious stimuli-induced neurotransmitter release from primary afferents at doses that are confirmed behaviorally as analgesic.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3,4-Dichloro-N-methyl-N-(2-(1-pyrrol...,
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics, Non-Narcotic,
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics, Opioid,
http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-,
http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, D-Penicillamine (2,5)-,
http://linkedlifedata.com/resource/pubmed/chemical/Morphine,
http://linkedlifedata.com/resource/pubmed/chemical/Naloxone,
http://linkedlifedata.com/resource/pubmed/chemical/Narcotic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurokinin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Substance P
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1529-2401
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
6
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3651-60
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15814796-3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-ben...,
pubmed-meshheading:15814796-Afferent Pathways,
pubmed-meshheading:15814796-Analgesics, Non-Narcotic,
pubmed-meshheading:15814796-Analgesics, Opioid,
pubmed-meshheading:15814796-Analysis of Variance,
pubmed-meshheading:15814796-Animals,
pubmed-meshheading:15814796-Behavior, Animal,
pubmed-meshheading:15814796-Dose-Response Relationship, Drug,
pubmed-meshheading:15814796-Drug Administration Routes,
pubmed-meshheading:15814796-Drug Interactions,
pubmed-meshheading:15814796-Electric Stimulation,
pubmed-meshheading:15814796-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-,
pubmed-meshheading:15814796-Enkephalin, D-Penicillamine (2,5)-,
pubmed-meshheading:15814796-Functional Laterality,
pubmed-meshheading:15814796-Immunochemistry,
pubmed-meshheading:15814796-Male,
pubmed-meshheading:15814796-Microscopy, Confocal,
pubmed-meshheading:15814796-Morphine,
pubmed-meshheading:15814796-Naloxone,
pubmed-meshheading:15814796-Narcotic Antagonists,
pubmed-meshheading:15814796-Pain Measurement,
pubmed-meshheading:15814796-Physical Stimulation,
pubmed-meshheading:15814796-Rats,
pubmed-meshheading:15814796-Rats, Sprague-Dawley,
pubmed-meshheading:15814796-Receptors, Neurokinin-1,
pubmed-meshheading:15814796-Spinal Cord,
pubmed-meshheading:15814796-Spinal Nerve Roots,
pubmed-meshheading:15814796-Substance P
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pubmed:year |
2005
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pubmed:articleTitle |
Inhibition by spinal mu- and delta-opioid agonists of afferent-evoked substance P release.
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pubmed:affiliation |
Department of Anesthesiology, University of California-San Diego, La Jolla, California 92093, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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