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.
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Szeged, P.O. Box 427, H-6701 Szeged, Hungary.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Farkas
authors.forename: Gabor
authors.initials: G
authors.lastname: Tuboly
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Benedek
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Horvath
mesh_terms: D000178:Acrylamides / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D019540:Area Under Curve; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000523:psychology; D007278:Injections, Spinal; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D013116:Spinal Cord / Q000187:drug effects*; D050916:TRPV Cation Channels / Q000187:drug effects
chemical_list: C500530:3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide; D000178:Acrylamides; D000700:Analgesics; D001095:Arachidonic Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D009842:Oligopeptides; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C474941:arachidonyl dopamine; C105293:endomorphin 1; C103505:AM 251; D004298:Dopamine