The antinociceptive effect of intrathecal kynurenic acid and its interaction with endomorphin-1 in rats

Gabriella Kekesi, Gabriella Joo, Emese Csullog, Ildiko Dobos, Walter Klimscha, Kalman Toth, György Benedek, Gyöngyi Horvath

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 μ-opioid receptor agonist peptide, endomorphin-1, was examined in the same set-up. Kynurenic acid at the higher doses (1-4 μg/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 μg/min) potentiated, but did not prolong, the antinociceptive effect of endomorphin-1 (0.1-1 μg/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.

Original languageEnglish
Pages (from-to)93-96
Number of pages4
JournalEuropean Journal of Pharmacology
Volume445
Issue number1-2
DOIs
Publication statusPublished - Jun 7 2002

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Keywords

  • Antinociception
  • Endogenous ligand
  • Intrathecal infusion
  • NMDA receptor antagonist
  • Opioid
  • Paw withdrawal test

ASJC Scopus subject areas

  • Pharmacology

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