Dose-independent antinociceptive interaction of endogenous ligands at the spinal level

Gabriella Kekesi, Gabriella Joo, Emese Csullog, Mihaly Peter-Szabo, Gyorgy Benedek, Gyongyi Horvath

Research output: Contribution to journalArticle

9 Citations (Scopus)


Adenosine, agmatine and kynurenic acid are endogenous ligands acting on different (e.g. adenosine, NMDA, α 2-adrenergic and imidazoline) receptors with a potential role in nociception at the spinal level. Their antinociceptive effects have already been investigated as monotherapy, but only a few studies have reported on their effects on the potency of other drugs. The purpose of the present study was carried out to analyse their interactions during continuous intrathecal co-administration in a carrageenan-induced thermal hyperalgesia model in rats. A paw withdrawal test was used for nociceptive testing. The intrathecal infusion (60 min) of these three drugs was administered alone or in combinations (kynurenic acid+adenosine or agmatine; adenosine+agmatine), which was followed by an additional 60-min observation period. Kynurenic acid alone was ineffective, while adenosine and agmatine alone caused a slight increase in pain threshold. However, independently of the applied doses all of the combinations significantly (p<0.05) increased the paw withdrawal latencies on the inflamed side during and after the infusion, but were almost ineffective on the normal side. The adenosine+kynurenic acid combination was the most effective: namely, that it relieved thermal hyperalgesia in all the applied dose combinations. Treatment with the kynurenic acid-containing combinations also caused dose-dependent side-effects (motor impairment and excitation), despite the fact that monotherapy with kynurenic acid in the applied dose (0.1 μg/min) did not result in adverse effects.

Original languageEnglish
Pages (from-to)93-102
Number of pages10
JournalBrain research
Issue number1
Publication statusPublished - Dec 10 2004



  • Adenosine
  • Agmatine
  • Imidazoline
  • Kynurenic acid
  • NMDA receptor
  • α -Adrenoceptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this