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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2003-10-21
pubmed:abstractText
We evaluated the ability of spinally administered nitric oxide (NO) synthase inhibitor to modulate antinociceptive action of intrathecal (i.t.) morphine in rats by measuring the early and late phases of flinching and licking/biting in the formalin test. To determine the contribution of spinal NO and glutamate, we measured the release of NO metabolites (nitrite/nitrate) and glutamate from the spinal cord in rats, using a microdialysis probe placed in the lumbar space. The i.t. administration of NG-nitro L-arginine methyl ester (L-NAME) produced a dose-dependent reduction in the number of flinches during the late phase, whereas there were no significant alterations in the late phase licking/biting, and early phase flinching and licking/biting. Spinal administration of morphine at low doses produced a significant antinociceptive activity in the early and late phases of the flinching behaviour, whereas higher doses of morphine were required to obtain a significant effect in the licking/biting behaviour during both phases. Combination of L-NAME with morphine resulted in an enhanced reduction in the early and late phase flinching. Enhanced antinociceptive activity was observed in the late phase licking/biting by i.t. combined administration of L-NAME (400 nmol) and morphine (1.25 nmol). In the present study, we have confirmed our prior results that injection of formalin (5.0%) into the plantar surface of the paw evoked a biphasic spinal release of nitrite/nitrate and a transient release of glutamate. Formalin-evoked release of nitrite/nitrate and glutamate was also reduced markedly by i.t. combined administration of L-NAME and morphine. These behavioural and biochemical results suggest that i.t. administered L-NAME may enhance morphine-induced antinociception through an increased inhibition of nitrite/nitrate and glutamate releases evoked by formalin injection at the spinal cord level.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
990
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
77-86
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:14568332-Analgesics, Opioid, pubmed-meshheading:14568332-Animals, pubmed-meshheading:14568332-Behavior, Animal, pubmed-meshheading:14568332-Drug Synergism, pubmed-meshheading:14568332-Enzyme Inhibitors, pubmed-meshheading:14568332-Extracellular Fluid, pubmed-meshheading:14568332-Formaldehyde, pubmed-meshheading:14568332-Glutamic Acid, pubmed-meshheading:14568332-Injections, Spinal, pubmed-meshheading:14568332-Male, pubmed-meshheading:14568332-Microdialysis, pubmed-meshheading:14568332-Morphine, pubmed-meshheading:14568332-NG-Nitroarginine Methyl Ester, pubmed-meshheading:14568332-Nitric Oxide, pubmed-meshheading:14568332-Nitric Oxide Synthase, pubmed-meshheading:14568332-Nitric Oxide Synthase Type I, pubmed-meshheading:14568332-Pain, pubmed-meshheading:14568332-Pain Measurement, pubmed-meshheading:14568332-Rats, pubmed-meshheading:14568332-Rats, Sprague-Dawley, pubmed-meshheading:14568332-Spinal Cord
pubmed:year
2003
pubmed:articleTitle
Evidence that nitric oxide-glutamate cascade modulates spinal antinociceptive effect of morphine: a behavioural and microdialysis study in rats.
pubmed:affiliation
Center for Laboratory Animal Science, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
pubmed:publicationType
Journal Article