Selective activation of cannabinoid CB2 receptors suppresses spinal fos protein expression and pain behavior in a rat model of inflammation
Selective activation of cannabinoid CB2 receptors suppresses spinal fos protein expression and pain behavior in a rat model of inflammation
复制标题
DOI：
10.1016/s0306-4522(03)00126-x
复制
发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Hohmann, AG
中科院分区：
文献类型：
--
作者：
Nackley, AG;Makriyannis, A;Hohmann, AG
激活大麻素CB2受体可减弱未经治疗的动物的热伤害性感受，但不能产生中枢调节效应，如体温过低和过敏症[Pain 93(2001)239]。本研究旨在验证一种假说，即外周C132的激活可以抑制炎症性疼痛的发展以及中枢神经系统水平的炎症诱发神经元活动。CB2选择性大麻素激动剂AM1241(100,330µg/kg ip.)抑制角叉菜胶致热性和机械性痛觉过敏和痛觉异常的发展。C132拮抗剂SR144528可阻断AM1241对角叉菜胶致行为敏化的抑制作用，而CB1拮抗剂SR141716A则不能阻断这一作用。足底注射AM1241(33µg/kg ipl)可抑制角叉菜胶注射后的痛觉过敏和痛觉过敏，但在对侧(非发炎)足掌注射AM1241后无效，与局部作用部位一致。在免疫细胞化学研究中，AM1241抑制了卡拉胶炎症模型中脊髓Fos蛋白的表达，这是神经元活动的标志。AM1241抑制角叉菜胶诱导的Fos蛋白在背角浅层和颈部的表达，但不抑制固有核和腹角的表达。SR144528可阻断AM1241对角叉菜胶诱导的Fos蛋白表达的抑制作用。这些数据提供了证据，证明大麻素CB2受体的作用足以抑制脊髓背角处理的吻端水平的炎症诱发的神经元活动，这与AM1241在炎症疼痛状态下正常化伤害性阈值和产生抗伤害性感觉的能力一致。(C)2003年IBRO。爱思唯尔科学有限公司出版。版权所有。
Activation of cannabinoid CB2 receptors attenuates thermal nociception in untreated animals while failing to produce centrally mediated effects such as hypothermia and catalepsy [Pain 93 (2001) 239]. The present study was conducted to test the hypothesis that activation of C132 in the periphery suppresses the development of inflammatory pain as well as inflammation-evoked neuronal activity at the level of the CNS. The CB2-selective cannabinoid agonist AM1241 (100, 330 mug/kg i.p.) suppressed the development of carrageenan-evoked thermal and mechanical hyperalgesia and allodynia. The AM1241-induced suppression of carrageenan-evoked behavioral sensitization was blocked by the C132 antagonist SR144528 but not by the CB1 antagonist SR141716A. Intraplantar (ipl) administration of AM1241 (33 mug/kg ipl) suppressed hyperalgesia and allodynia following administration to the carrageenan-injected paw but was inactive following administration in the contralateral (noninflamed) paw, consistent with a local site of action. In immunocytochemical studies, AM1241 suppressed spinal Fos protein expression, a marker of neuronal activity, in the carrageenan model of inflammation. AM1241 suppressed carrageenan-evoked Fos protein expression in the superficial and neck region of the dorsal horn but not in the nucleus proprius or the ventral horn. The suppression of carrageenan-evoked Fos protein expression induced by AM1241 was blocked by coadministration of SR144528 in all spinal laminae. These data provide evidence that actions at cannabinoid CB2 receptors are sufficient to suppress inflammation-evoked neuronal activity at rostral levels of processing in the spinal dorsal horn, consistent with the ability of AM1241 to normalize nociceptive thresholds and produce antinociception in inflammatory pain states. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.