Blockade of central cyclooxygenase (COX) pathways enhances the cannabinold-induced antinociceptive effects on inflammatory temporomandibular joint (TMJ) nociception
Blockade of central cyclooxygenase (COX) pathways enhances the cannabinold-induced antinociceptive effects on inflammatory temporomandibular joint (TMJ) nociception
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DOI：
10.1016/j.pain.2007.01.015
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发表时间：
2007-11-01
期刊：
影响因子：
7.4
通讯作者：
Mokha, Sukhbir S.
中科院分区：
文献类型：
--
作者：
Ahn, Dong K.;Choi, Hyo S.;Mokha, Sukhbir S.
本研究首次探讨了中枢环氧合酶（考克斯）通路参与调节脑池内注射大麻素对自由活动大鼠颞下颌关节（TMJ）炎症引起的伤害性感受的抗伤害性感受作用。在颞下颌关节内注射5%福尔马林后，在Sprague-Dawley大鼠中记录9个连续5分钟间隔的伤害性抓挠行为。与溶剂处理组相比，在福尔马林注射前20分钟脑池内注射30 μ g WIN 55，212 -2（一种合成的非亚型选择性CB 1/2激动剂）可显著减少福尔马林诱导的抓挠次数和抓挠持续时间。脑池内注射10 μ g AM 251（一种CB 1受体选择性拮抗剂）可阻断WIN 55，212 -2的抗伤害效应，但不被AM 630（一种CB 2受体选择性拮抗剂）阻断。在脑池内给予NS-398（一种选择性考克斯-2抑制剂）、吲哚美辛（一种非选择性考克斯1/2抑制剂）、对乙酰氨基酚（一种假定的考克斯-3抑制剂）后，10 μ g剂量的WIN 55，212 -2在产生抗伤害感受方面无效，但在用选择性考克斯-1抑制剂SC-560预处理后无效。NS-398治疗组中WIN 55，212 -2的ED 50值显著低于载体治疗组。重要的是，单独给予低剂量的考克斯抑制剂不会减弱伤害性感受。这些结果表明，中枢考克斯通路的抑制，可能是通过考克斯-2抑制，通过增强大麻素诱导的抗伤害感受效应来减轻炎性疼痛。根据我们的观察，大麻素与考克斯抑制剂联合给药可能在治疗炎症性颞下颌关节疼痛方面具有治疗前景。(C)2007年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
The present study is the first to investigate the participation of central cyclooxygenase (COX) pathways in modulating the antinociceptive effects of intracisternally administered cannabinoid on nociception induced by inflammation of the temporomandibular joint (TMJ) in freely moving rats. Following intra-articular injection of 5% formalin in the TMJ, nociceptive scratching behavior was recorded for nine successive 5-min intervals in Sprague-Dawley rats. Intracisternal injection of 30 mu g of WIN 55,212-2, a synthetic non-subtype-selective CB1/2 agonist, administered 20 min prior to formalin injection significantly reduced the number of scratches and duration of scratching induced by formalin compared with the vehicle-treated group. Antinociceptive effect of WIN 55,212-2 was blocked by intracisternal injection of 10 mu g of AM251, a CB1 receptor-selective antagonist, but not by AM630, a CB2 receptor-selective antagonist. A 10 mu g dose of WIN 55,212-2 that was ineffective in producing antinociception became effective following intracisternal administration of NS-398, a selective COX-2 inhibitor; indomethacin, a non-selective COX 1/2 inhibitor; acetaminophen, a putative COX-3 inhibitor, but not following pretreatment with the selective COX-1 inhibitor, SC-560. The ED50 value of WIN 55,212-2 in the NS-398-treated group was significantly lower than that in the vehicle-treated group. Importantly, administration of low doses of COX inhibitors alone did not attenuate nociception. These results indicate that inhibition of central COX pathways, presumably via COX-2 inhibition, reduces inflammatory pain by enhancing the cannabinoid-induced antinociceptive effect. Based on our observations, combined administration of cannabinoids with COX inhibitors may hold a therapeutic promise in the treatment of inflammatory TMJ pain. (C) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.