Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2005-4-7
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3651-60
pubmed:dateRevised
2007-11-14
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
pubmed:year
2005
pubmed:articleTitle
Inhibition by spinal mu- and delta-opioid agonists of afferent-evoked substance P release.
pubmed:affiliation
Department of Anesthesiology, University of California-San Diego, La Jolla, California 92093, USA.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural