title: The antinociceptive effect of intrathecal kynurenic acid and its interaction with endomorphin-1 in rats.
abstract: Kynurenic acid as an endogenous ligand antagonizes all types of ionotropic glutamate receptors, with preferential affinity for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor. The purpose of the present study was to investigate the antinociceptive potency of continuously administered kynurenic acid on carrageenan-induced thermal hyperalgesia by means of a paw withdrawal test in awake rats. The possible interaction between kynurenic acid and the endogenous mu-opioid receptor agonist peptide, endomorphin-1, was examined in the same set-up. Kynurenic acid at the higher doses (1-4 microg/min) significantly decreased the thermal hyperalgesia and increased the paw withdrawal latencies on the non-inflamed side. These doses were also associated with motor impairment on both sides. Low doses of kynurenic acid (0.01-0.1 microg/min) potentiated, but did not prolong, the antinociceptive effect of endomorphin-1 (0.1-1 microg/min) on the inflamed side. There was no sign of motor impairment during the combined treatment. These findings demonstrate that the combination of low doses of these two endogenous ligands provides effective and well-controlled antinociception without side effects.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, P.O. Box 427, H-6701, Szeged, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Kekesi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Joo
authors.forename: Emese
authors.initials: E
authors.lastname: Csullog
authors.forename: Ildiko
authors.initials: I
authors.lastname: Dobos
authors.forename: Walter
authors.initials: W
authors.lastname: Klimscha
authors.forename: Kalman
authors.initials: K
authors.lastname: Toth
authors.forename: György
authors.initials: G
authors.lastname: Benedek
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Horvath
mesh_terms: D000700:Analgesics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004357:Drug Synergism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D007260:Infusion Pumps; D007278:Injections, Spinal; D007736:Kynurenic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats
chemical_list: D000700:Analgesics; D009842:Oligopeptides; C105293:endomorphin 1; D007736:Kynurenic Acid