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• W1970023477 abstract "BACKGROUND: Several data suggest that both opioid and N-methyl-d-aspartate (NMDA) receptors are localized at the peripheral level, and drugs acting on these receptors may produce antinociception after topical administration; however, the antinociceptive effect of endogenous ligands at these receptors is poorly clarified. Our goal in this study was to determine the antinociceptive potency of the endogenous opioid peptide, endomorphin-1 (EM1), and the endogenous NMDA receptor antagonist, kynurenic acid (KYNA), and their interaction at the peripheral level in the rat inflamed joint model. METHODS: Mechanical hypersensitivity was produced by injection of carrageenan (300 μg/20 μL) into the tibiotarsal joint of the right hind leg. The mechanical pain threshold was assessed by von Frey filaments (0.064-110 g). EM1 (30, 100, and 200 μg), KYNA (30, 100, 200, and 400 μg), and their combinations in a fixed-dose ratio (1:1) were injected into the inflamed joint, and the pain threshold was determined repeatedly for 75 min after the drug administrations. RESULTS: Neither EM1 nor KYNA administered to the inflamed joint influenced the pain threshold at the noninflamed side. Both ligands produced dose-dependent antihyperalgesia, and the highest doses caused a prolonged effect. EM1 had higher potency (30% effective dose [ED30] and 50% effective dose [ED50] values were 112 μg [confidence interval {CI}: 80-146] and 167 μg [CI: 135-220], respectively) compared with KYNA (ED30 and ED50 values were 204 μg [CI: 160-251] and 330 μg [CI: 280-407], respectively). The antinociceptive effect of EM1 was prevented by subcutaneous naltrexone pretreatment. The coadministration of EM1 with KYNA caused an enhanced and/or prolonged antinociceptive effect. The ED30 and ED50 values of the combination were 141 μg [CI: 83-182] and 231 μg [CI: 190-293], respectively, which did not differ significantly from the theoretically additive values (ED30 and ED50 values were 145 μg [CI: 68-237] and 220 μg [CI: 144-230], respectively), thus the interaction between these ligands is additive. None of the treatments caused any sign of side effects. CONCLUSION: Peripherally administered endogenous opioid agonist and NMDA receptor antagonist ligands might be beneficial in inflammatory pain. Because both drugs barely cross the blood-brain barrier, their local administration causes no central side effects." @default.
• W1970023477 created "2016-06-24" @default.
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• W1970023477 date "2009-10-01" @default.
• W1970023477 modified "2023-10-03" @default.
• W1970023477 title "The Peripheral Antinociceptive Effects of Endomorphin-1 and Kynurenic Acid in the Rat Inflamed Joint Model" @default.
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• W1970023477 doi "https://doi.org/10.1213/ane.0b013e3181b21c5e" @default.
• W1970023477 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19762760" @default.
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