Amaya Fumimasa, Shimosato Goshun, Kawasaki Yasuhiko, Hashimoto Satoru, Tanaka Yoshifumi, Ji Ru-Rong, Tanaka Masaki
Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Pain. 2006 Sep;124(1-2):175-83. doi: 10.1016/j.pain.2006.04.001. Epub 2006 May 18.
Cannabinoids act on various regions in the nervous system to modulate neuronal activity including nociception. Here, we investigated CB1 receptor expression in primary afferent neurons in the dorsal root ganglion (DRG) and the efficacy of a local (intraplantar) application of the selective CB1 agonist, 2-arachidonyl-2-chloroethylamide (ACEA), on inflammatory thermal hyperalgesia. In situ hybridization showed normal CB1 mRNA expression in 28% of DRG neurons. Peripheral inflammation by CFA (complete Freund's adjuvant) significantly increased the ratio of CB1 mRNA-positive neurons to 43%, primarily with increase in NF200-negative C-fiber nociceptors. Furthermore, CB1 and TRPV1 (transient potential receptor vanilloid subtype-1) co-localization was increased from 41% before inflammation to 67% two days after inflammation. Inflammation also increased CB1 immunoreactivity in DRG neurons and in nerve fibers of the hindpaw dermis, indicating increased CB1 transport from the cell body to the peripheral nerve. The intraplantar application of ACEA attenuated CFA-induced thermal hyperalgesia. The antinociceptive properties of ACEA became more prominent at 2 days after inflammation, compared with those in non-inflamed and inflamed animals at 8 h. These results suggest that CB1 expression in primary afferent neurons is increased by inflammation and that the subsequent increase in CB1 transport to peripheral axons contributes to the increased antihyperalgesic efficacy of locally administered CB1 agonist.
大麻素作用于神经系统的各个区域，以调节包括伤害感受在内的神经元活动。在此，我们研究了背根神经节（DRG）初级传入神经元中CB1受体的表达，以及局部（足底内）应用选择性CB1激动剂2-花生四烯酰-2-氯乙酰胺（ACEA）对炎性热痛觉过敏的疗效。原位杂交显示，28%的DRG神经元中CB1 mRNA表达正常。完全弗氏佐剂（CFA）引起的外周炎症显著增加了CB1 mRNA阳性神经元的比例，达到43%，主要是NF200阴性C纤维伤害感受器增加。此外，CB1与瞬时受体电位香草酸亚型1（TRPV1）的共定位从炎症前的41%增加到炎症后两天的67%。炎症还增加了DRG神经元和后爪真皮神经纤维中的CB1免疫反应性，表明CB1从细胞体向周围神经的转运增加。足底内应用ACEA可减轻CFA诱导的热痛觉过敏。与未发炎和发炎8小时的动物相比，ACEA的镇痛特性在炎症后2天更为显著。这些结果表明，炎症会增加初级传入神经元中CB1的表达，随后CB1向周围轴突转运的增加有助于局部应用CB1激动剂的抗痛觉过敏疗效增强。
