Activation of CB1 and CB2 receptors attenuates the induction and maintenance of inflammatory pain in the rat
Activation of CB1 and CB2 receptors attenuates the induction and maintenance of inflammatory pain in the rat
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DOI：
10.1016/j.pain.2005.09.005
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发表时间：
2005-12-05
期刊：
影响因子：
7.4
通讯作者：
Chapman, V
中科院分区：
文献类型：
--
作者：
Elmes, SJR;Winyard, LA;Chapman, V
本研究的目的是研究大麻素激动剂对已建立的炎性痛觉过敏的影响。我们比较了在炎性痛觉过敏的角叉菜胶模型中，有效的非选择性大麻素激动剂HU 210和选择性CB受体激动剂JWH-133的给药前与给药后对后爪承重和爪水肿的影响。为了比较的目的，我们还确定了IT-阿片受体激动剂吗啡和COX 2抑制剂罗非昔布在这个模型中的作用。在足底内注射角叉菜胶（2%，100 μ l）后3小时，与载体处理的大鼠相比，同侧后爪的负重显著（P < 0.001）减少，并且与载体处理的大鼠相比，同侧后爪体积伴随增加（P < 0.001）。在注射角叉菜胶后3小时全身给予HU 210（10 μ g/kg）和JWH-133（10 mg/kg），显著减弱了同侧后爪承重（两者P < 0.05）和爪体积（两者P < 0.001）的减少。预先给予HU 210和JWH-133对该模型的负重作用相似。预施用HU 210还显著降低角叉菜胶诱导的爪体积变化（P < 0.001），JWH-133的情况并非如此。后施用HU 210和JWH-133对同侧后爪承重和爪体积的作用与全身后施用吗啡和罗非昔布（两者均为3 mg/kg）的作用相当。总之，HU 210和JWH-133都减弱了已建立的炎性超敏反应和肿胀，表明基于大麻素的药物具有治疗已建立的炎性疼痛反应的临床潜力。(c)2005年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
The aim of the present study was to investigate the effects of cannabinoid agonists on established inflammatory hyperalgesia. We have compared the effects of pre-administration versus post-administration of a potent non-selective cannabinoid agonist HU210 and a selective CB, receptor agonist JWH-133 on hindpaw weight bearing and paw oedema in the carrageenan model of inflammatory hyperalgesia. For comparative purposes we also determined the effects of the It-opioid receptor agonist morphine and the COX2 inhibitor rofecoxib in this model. At 3 h following intraplantar injection of carrageenan (2%, 100 mu l) there was a significant (P < 0.001) reduction in weight bearing on the ipsilateral hindpaw, compared to vehicle treated rats and a concomitant increase in ipsilateral hindpaw volume (P < 0.001), compared to vehicle treated rats. Systemic administration of HU210 (10 mu g/kg) and JWH-133 (10 mg/kg) at 3 h following injection of carrageenan, significantly attenuated decreases in ipsilateral hindpaw weight bearing (P < 0.05 for both) and paw volume (P < 0.001 for both). Preadministration of HU210 and JWH-133 had similar effects on weight bearing in this model. Pre-administered HU210 also significantly decreased carrageenan-induced changes in paw volume (P < 0.001), this was not the case for JWH-133. Effects of post-administered HU210 and JWH-133 on ipsilateral hindpaw weight bearing and paw volume were comparable to the effect of systemic post-administration of morphine and rofecoxib (3 mg/kg for both). In summary, both HU210 and JWH-133 attenuated established inflammatory hypersensitivity and swelling, suggesting that cannabinoid-based drugs have clinical potential for the treatment of established inflammatory pain responses. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.