The antinociceptive potency of N-arachidonoyl-dopamine (NADA) and its interaction with endomorphin-1 at the spinal level

Ibolya Farkas, Gabor Tuboly, G. Benedek, G. Horváth

Research output: Article

6 Citations (Scopus)

Abstract

The endogenous N-arachidonoyl-dopamine (NADA) activates both transient receptor potential vanilloid1 (TRPV1) and cannabinoid-1 (CB 1) receptors. The goal of this study was to characterize the antinociceptive potential of NADA on inflammatory thermal hyperalgesia in rats at spinal level, and to determine its interaction with endomorphin-1 (EM) at the spinal level. The effects of NADA and EM on thermal hyperalgesia were evaluated in rats with a unilateral hind paw carrageenan-induced inflammation. Intrathecal injection of either EM (0.03-10 μg) or NADA (1.5-50 μg) caused dose-dependent antihyperalgesia, but NADA was 5.4 times less potent than EM. The antihyperalgesia caused by 15 μg NADA was inhibited by the TRPV1 antagonist AMG9810, but not by CB 1 antagonist/inverse agonist AM 251, whereas the effect of 50 μg NADA was decreased by both drugs. Co-administration of EM with NADA in 1:15 and 1:50 ratios produced a short-lasting potentiation, but isobolographic analysis for the whole investigated period revealed additive interaction between the two endogenous ligands. The results show that both TRPV1 and CB 1 receptor activation play a substantial role in the antinociceptive effects of NADA at spinal level, while co-administration of NADA with EM did not show potentiation.

Original languageEnglish
Pages (from-to)731-737
Number of pages7
JournalPharmacology, Biochemistry and Behavior
Volume99
Issue number4
DOIs
Publication statusPublished - okt. 2011

Fingerprint

Dopamine
Cannabinoids
Cannabinoid Receptors
Hyperalgesia
Rats
endomorphin 1
Cannabinoid Receptor Antagonists
Spinal Injections
Carrageenan
Chemical activation
Ligands
Inflammation
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

Cite this

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title = "The antinociceptive potency of N-arachidonoyl-dopamine (NADA) and its interaction with endomorphin-1 at the spinal level",
abstract = "The endogenous N-arachidonoyl-dopamine (NADA) activates both transient receptor potential vanilloid1 (TRPV1) and cannabinoid-1 (CB 1) receptors. The goal of this study was to characterize the antinociceptive potential of NADA on inflammatory thermal hyperalgesia in rats at spinal level, and to determine its interaction with endomorphin-1 (EM) at the spinal level. The effects of NADA and EM on thermal hyperalgesia were evaluated in rats with a unilateral hind paw carrageenan-induced inflammation. Intrathecal injection of either EM (0.03-10 μg) or NADA (1.5-50 μg) caused dose-dependent antihyperalgesia, but NADA was 5.4 times less potent than EM. The antihyperalgesia caused by 15 μg NADA was inhibited by the TRPV1 antagonist AMG9810, but not by CB 1 antagonist/inverse agonist AM 251, whereas the effect of 50 μg NADA was decreased by both drugs. Co-administration of EM with NADA in 1:15 and 1:50 ratios produced a short-lasting potentiation, but isobolographic analysis for the whole investigated period revealed additive interaction between the two endogenous ligands. The results show that both TRPV1 and CB 1 receptor activation play a substantial role in the antinociceptive effects of NADA at spinal level, while co-administration of NADA with EM did not show potentiation.",
keywords = "Cannabinoid, Endomorphin-1, Hyperalgesia, Interaction, Intrathecal, Pain, Poly-pharmacology, TRPV1 receptor",
author = "Ibolya Farkas and Gabor Tuboly and G. Benedek and G. Horv{\'a}th",
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AU - Farkas, Ibolya

AU - Tuboly, Gabor

AU - Benedek, G.

AU - Horváth, G.

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N2 - The endogenous N-arachidonoyl-dopamine (NADA) activates both transient receptor potential vanilloid1 (TRPV1) and cannabinoid-1 (CB 1) receptors. The goal of this study was to characterize the antinociceptive potential of NADA on inflammatory thermal hyperalgesia in rats at spinal level, and to determine its interaction with endomorphin-1 (EM) at the spinal level. The effects of NADA and EM on thermal hyperalgesia were evaluated in rats with a unilateral hind paw carrageenan-induced inflammation. Intrathecal injection of either EM (0.03-10 μg) or NADA (1.5-50 μg) caused dose-dependent antihyperalgesia, but NADA was 5.4 times less potent than EM. The antihyperalgesia caused by 15 μg NADA was inhibited by the TRPV1 antagonist AMG9810, but not by CB 1 antagonist/inverse agonist AM 251, whereas the effect of 50 μg NADA was decreased by both drugs. Co-administration of EM with NADA in 1:15 and 1:50 ratios produced a short-lasting potentiation, but isobolographic analysis for the whole investigated period revealed additive interaction between the two endogenous ligands. The results show that both TRPV1 and CB 1 receptor activation play a substantial role in the antinociceptive effects of NADA at spinal level, while co-administration of NADA with EM did not show potentiation.

AB - The endogenous N-arachidonoyl-dopamine (NADA) activates both transient receptor potential vanilloid1 (TRPV1) and cannabinoid-1 (CB 1) receptors. The goal of this study was to characterize the antinociceptive potential of NADA on inflammatory thermal hyperalgesia in rats at spinal level, and to determine its interaction with endomorphin-1 (EM) at the spinal level. The effects of NADA and EM on thermal hyperalgesia were evaluated in rats with a unilateral hind paw carrageenan-induced inflammation. Intrathecal injection of either EM (0.03-10 μg) or NADA (1.5-50 μg) caused dose-dependent antihyperalgesia, but NADA was 5.4 times less potent than EM. The antihyperalgesia caused by 15 μg NADA was inhibited by the TRPV1 antagonist AMG9810, but not by CB 1 antagonist/inverse agonist AM 251, whereas the effect of 50 μg NADA was decreased by both drugs. Co-administration of EM with NADA in 1:15 and 1:50 ratios produced a short-lasting potentiation, but isobolographic analysis for the whole investigated period revealed additive interaction between the two endogenous ligands. The results show that both TRPV1 and CB 1 receptor activation play a substantial role in the antinociceptive effects of NADA at spinal level, while co-administration of NADA with EM did not show potentiation.

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