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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >The antinociceptive potency of N-arachidonoyl-dopamine (NADA) and its interaction with endomorphin-1 at the spinal level.
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The antinociceptive potency of N-arachidonoyl-dopamine (NADA) and its interaction with endomorphin-1 at the spinal level.

机译：N-花生四烯酸-多巴胺（NADA）的抗伤害力及其在脊髓水平上与Endomorphin-1的相互作用。

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摘要

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 mug) or NADA (1.5-50 mug) caused dose-dependent antihyperalgesia, but NADA was 5.4 times less potent than EM. The antihyperalgesia caused by 15 mug NADA was inhibited by the TRPV1 antagonist AMG9810, but not by CB(1) antagonist/inverse agonist AM 251, whereas the effect of 50 mug 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.
机译：内源性N-花生四烯酸-多巴胺（NADA）激活瞬态受体电位vanilloid1（TRPV1）和大麻素1（CB（1））受体。这项研究的目的是在脊髓水平上表征NADA对炎性热痛觉过敏的抗伤害感受能力，并确定其在脊髓水平上与内啡肽-1（EM）的相互作用。评估了NADA和EM对单侧后爪角叉菜胶诱发炎症的大鼠的热痛觉过敏的作用。鞘内注射EM（0.03-10杯）或NADA（1.5-50杯）引起剂量依赖性抗痛觉过敏，但NADA的效力比EM低5.4倍。由15杯NADA引起的抗痛觉过敏被TRPV1拮抗剂AMG9810抑制，但未被CB（1）拮抗剂/反向激动剂AM 251抑制，而两种药物均降低了50杯NADA的作用。 EM与NADA以1:15和1:50的比例共同给药产生了短暂的增强作用，但是在整个研究期间的等效线谱分析表明，这两种内源性配体之间存在加性相互作用。结果表明，TRPV1和CB（1）受体激活在脊髓水平上对NADA的镇痛作用中起着重要作用，而NADA与EM并用未显示出增强作用。

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