Opioid receptor and NO/cGMP pathway as a mechanism of peripheral antinociceptive action of the cannabinoid receptor agonist anandamide

LIFE SCIENCES

卷:85

Article

Lopes Reis, Glaucia Maria¹  Pacheco, Daniela¹  Perez, Andrea Castro¹  Klein, Andre¹  Ramos, Marina Abadia¹  Gama Duarte, Igor Dimitri¹ 

[1] Univ Fed Minas Gerais, ICB, Dept Farmacol, BR-31270100 Belo Horizonte, MG, Brazil

关键词: Anandamide;    L-arginine/NO/cGMP pathway;    Peripheral antihyperalgesia;    Cannabinoids;    Opioids;   

DOI  :  10.1016/j.lfs.2009.06.012

来源: Elsevier

【 摘 要 】

Aims: In this study, we investigated whether the opioid system and the nitric oxide pathway were involved in the peripheral antinociception induced by a cannabinoid receptor agonist anandamide. Main methods: Hyperalgesia was induced by a subcutaneous injection of carrageenan (250 mu g) into the plantar surface of the rat's hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams (g) required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. Key findings: Anandamide elicited a dose-dependent (50, 75, and 100 ng per paw) antinociceptive effect. The highest dose of anandamide did not produce anti hyperalgesia in the contralateral paw, indicating a peripheral site of action. The CB1 receptor antagonist AM251 (20, 40, 80 and 160 mu g per paw) antagonized peripheral antihyperalgesia induced by anandamide ( 100 ng), in a dose-dependent manner, suggesting CB1 receptor activation. Anandamide-induced peripheral anti hyperalgesia was reverted by blockers of the L-arginine/NO/cGMP pathway N-G-nitro-L-arginine (NOARG; 24, 36 and 48 mu g per paw) and 1H-[1,2,4] Oxadiazolo[4,3-a] quinoxalin-1-one (ODQ: 25,50 and 100 mu g per paw), in a dose-dependent manner. Furthermore, opioid receptor antagonist naloxone (12.5, 25 and 50 mu g per paw) antagonized the peripheral antihyperalgesia induced by anandamide. Significance: This study provides evidence that the peripheral antinociceptive effect of the cannabinoid receptor agonist anandamide may result from L-arginine/NO/cGMP pathway activation and that the opioid system is also involved. (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

Free