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

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 stu...

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Bibliographic Details
Published in:Brain research 2004-12, Vol.1029 (1), p.93-102
Main Authors: Kekesi, Gabriella, Joo, Gabriella, Csullog, Emese, Peter-Szabo, Mihaly, Benedek, Gyorgy, Horvath, Gyongyi
Format: Article
Language:English
Subjects:
Adenosine
Adenosine - administration & dosage
Agmatine
Agmatine - administration & dosage
Analgesics - administration & dosage
Animals
Biological and medical sciences
Carrageenan
Dose-Response Relationship, Drug
Drug Combinations
Drug Synergism
Excitatory Amino Acid Antagonists - administration & dosage
Fundamental and applied biological sciences. Psychology
Hyperalgesia - chemically induced
Imidazoline
Injections, Spinal
Kynurenic acid
Kynurenic Acid - administration & dosage
Ligands
Male
NMDA receptor
Pain Threshold - drug effects
Rats
Rats, Wistar
Reaction Time - drug effects
Somesthesis and somesthetic pathways (proprioception, exteroception, nociception)
interoception
electrolocation. Sensory receptors
Vertebrates: nervous system and sense organs
α 2-Adrenoceptor
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Summary: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
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2004.09.039