Rodella Luigi F, Borsani Elisa, Rezzani Rita, Ricci Francesca, Buffoli Barbara, Bianchi Rossella
Department of Biomedical Sciences and Biotechnology, Division of Human Anatomy, University of Brescia, viale Europa 11, 25123 Brescia, Italy.
Eur J Pharmacol. 2005 Jan 31;508(1-3):139-46. doi: 10.1016/j.ejphar.2004.12.031. Epub 2005 Jan 12.
Cannabinoids like anandamide are involved in pain transmission. In this study we evaluated the effects of administrating N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404), an inhibitor of anandamide reuptake and monitoring the expression of c-fos, a marker of activated neurons in an experimental model of neuropathic pain (sciatic nerve tying). Fos expression was monitored 14 days after tying of sciatic nerve and 2 h after non-noxious stimulation. We showed that non-noxious stimulation increased Fos-positivity in the dorsal superficial laminae of the lumbar spinal cord of tied animals but not in the control animals. AM404 significantly reduced Fos induction in tied animals. Co-administration of cannabinoid CB1 receptor, cannabinoid CB2 receptor and transient receptor potential vanilloid type 1 (TRPV-1) antagonists reduced the effect of AM404 and this reduction was higher using cannabinoid CB1 receptor antagonist. These results suggest that AM404 could be a useful drug to reduce neuropathic pain and that cannabinoid CB1 receptor, cannabinoid CB2 receptor and vanilloid TRPV-1 receptor are involved.
像花生四烯乙醇胺这样的大麻素参与疼痛传递。在本研究中，我们评估了给予N-(4-羟基苯基)-5Z,8Z,11Z,14Z-二十碳四烯酰胺（AM404）（一种花生四烯乙醇胺再摄取抑制剂）的效果，并监测了c-fos的表达，c-fos是神经性疼痛实验模型（坐骨神经结扎）中活化神经元的标志物。在坐骨神经结扎后14天以及非伤害性刺激后2小时监测Fos表达。我们发现，非伤害性刺激增加了结扎动物腰脊髓背侧浅层的Fos阳性，但对照动物未出现这种情况。AM404显著降低了结扎动物中的Fos诱导。大麻素CB1受体、大麻素CB2受体和瞬时受体电位香草酸亚型1（TRPV-1）拮抗剂的共同给药降低了AM404的作用，并且使用大麻素CB1受体拮抗剂时这种降低更为明显。这些结果表明，AM404可能是一种减轻神经性疼痛的有用药物，并且大麻素CB1受体、大麻素CB2受体和香草酸TRPV-1受体参与其中。
