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.

• Authors: Ibolya Farkas, Gabor Tuboly, Gyorgy Benedek, Gyongyi Horvath
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 99 Issue 4 Pg. 731-7 (Oct 2011) ISSN: 1873-5177 [Electronic] United States
• PMID: 21624393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• 3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide
• Acrylamides
• Analgesics
• Arachidonic Acids
• Bridged Bicyclo Compounds, Heterocyclic
• Oligopeptides
• Piperidines
• Pyrazoles
• Receptor, Cannabinoid, CB1
• TRPV Cation Channels
• Trpv1 protein, rat
• arachidonyl dopamine
• endomorphin 1
• AM 251
• Dopamine

Topics

• Acrylamides (pharmacology)
• Analgesics
• Animals
• Arachidonic Acids (pharmacology)
• Area Under Curve
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Dopamine (analogs & derivatives, pharmacology)
• Dose-Response Relationship, Drug
• Drug Synergism
• Hot Temperature
• Hyperalgesia (drug therapy, psychology)
• Injections, Spinal
• Male
• Oligopeptides (pharmacology)
• Pain Measurement (drug effects)
• Piperidines (pharmacology)
• Pyrazoles (pharmacology)
• Rats
• Rats, Wistar
• Receptor, Cannabinoid, CB1 (agonists)
• Spinal Cord (drug effects)
• TRPV Cation Channels (drug effects)