Borsani Elisa, Labanca Mauro, Bianchi Rossella, Rodella Luigi F
Department of Biomedical Sciences and Biotechnologies, Division of Human Anatomy, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Brain Res. 2007 Jun 4;1152:87-94. doi: 10.1016/j.brainres.2007.03.071. Epub 2007 Mar 28.
Cannabinoids, such as anandamide, are involved in pain transmission. We evaluated the effects of AM404 (N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide), an anandamide reuptake inhibitor, monitoring the expression of c-fos, a marker of activated neurons and the pain-related behaviours using formalin test. The study was carried out in an experimental model of inflammatory pain made by a single injection of formalin in rat hind paws. Formalin test showed that the antinociceptive effect of AM404 was evident in phase I. We found that Fos-positive neurons in dorsal superficial and deep laminae of the lumbar spinal cord increased in formalin-injected animals and that AM404 significantly reduced Fos induction. Co-administration of cannabinoid CB(1) receptor antagonist (AM251), cannabinoid CB(2) receptor antagonist (AM630) and transient receptor potential vanilloid type 1 (TRPV-1) antagonist (capsazepine), attenuate the inhibitory effect of AM404 and this effect was higher using cannabinoid CB(2) and vanilloid TRPV-1 receptor antagonists. These results suggest that AM404 could be a useful drug to reduce inflammatory pain in our experimental model and that cannabinoid CB(2) receptor and vanilloid TRPV-1 receptor, and to a lesser extent, the cannabinoid CB(1) receptor are involved.
大麻素，如花生四烯乙醇胺，参与疼痛传递。我们评估了花生四烯乙醇胺再摄取抑制剂AM404（N-(4-羟基苯基)-5Z,8Z,11Z,14Z-二十碳四烯酰胺）的作用，通过福尔马林试验监测c-fos的表达（一种活化神经元的标志物）以及疼痛相关行为。该研究在大鼠后爪单次注射福尔马林制成的炎性疼痛实验模型中进行。福尔马林试验表明，AM404在第一阶段的抗伤害感受作用明显。我们发现，在注射福尔马林的动物中，腰脊髓背侧浅层和深层的Fos阳性神经元增加，而AM404显著减少Fos诱导。大麻素CB(1)受体拮抗剂（AM251）、大麻素CB(2)受体拮抗剂（AM630）和瞬时受体电位香草酸亚型1（TRPV-1）拮抗剂（辣椒素）共同给药，减弱了AM404的抑制作用，并且使用大麻素CB(2)和香草酸TRPV-1受体拮抗剂时这种作用更强。这些结果表明，在我们的实验模型中，AM404可能是一种减轻炎性疼痛的有用药物，并且大麻素CB(2)受体和香草酸TRPV-1受体以及程度较轻的大麻素CB(1)受体参与其中。
