Induction of CB1 cannabinoid receptor by inflammation in primary afferent neurons facilitates antihyperalgesic effect of peripheral CB1 agonist
Induction of CB1 cannabinoid receptor by inflammation in primary afferent neurons facilitates antihyperalgesic effect of peripheral CB1 agonist
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DOI：
10.1016/j.pain.2006.04.001
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发表时间：
2006-09-01
期刊：
影响因子：
7.4
通讯作者：
Tanaka, Masaki
中科院分区：
文献类型：
--
作者：
Amaya, Fumimasa;Shimosato, Goshun;Tanaka, Masaki
大麻素作用于神经系统中的各个区域以调节神经元活动，包括伤害感受。在这里，我们研究了CB 1受体表达的初级传入神经元在背根神经节（DRG）和局部（足底）应用的选择性CB 1激动剂，2-花生四烯酸-2-氯乙酰胺（ACEA），炎症热痛觉过敏的疗效。原位杂交结果显示，28%的DRG神经元中CB 1 mRNA表达正常。CFA（完全弗氏佐剂）引起的外周炎症显著增加了CB 1 mRNA阳性神经元的比例至43%，主要是NF 200阴性C纤维伤害感受器的增加。此外，CB 1和TRPVI（瞬时电位受体香草酸亚型-1）共定位从炎症前的41%增加到炎症后两天的67%。炎症还增加了背根神经节神经元和后爪真皮的神经纤维中的CB 1免疫反应性，表明CB 1从细胞体到外周神经的运输增加。ACEA的足底应用衰减CFA诱导的热痛觉过敏。ACEA的镇痛作用在致炎后2天开始增强，与非致炎和致炎后8 h相比，差异有显著性。这些结果表明，在初级传入神经元中的CB 1表达增加炎症和随后的CB 1运输到外周轴突的增加有助于局部施用的CB 1激动剂的抗痛觉过敏功效的增加。(c)2006年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
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 TRPVI (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. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.