EVIDENCE FOR ANTI-INFLAMMATORY AND PUTATIVE ANALGESIC EFFECTS OF A MONOCLONAL ANTIBODY TO CALCITONIN GENE-RELATED PEPTIDE
EVIDENCE FOR ANTI-INFLAMMATORY AND PUTATIVE ANALGESIC EFFECTS OF A MONOCLONAL ANTIBODY TO CALCITONIN GENE-RELATED PEPTIDE
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DOI：
10.1016/j.neuroscience.2012.10.030
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发表时间：
2013-01-01
期刊：
影响因子：
3.3
通讯作者：
Boissonade, F. M.
中科院分区：
文献类型：
--
作者：
Bowler, K. E.;Worsley, M. A.;Boissonade, F. M.
背景：降钙素基因相关肽(CGRP)是一种强大的促炎介质，被认为在炎症和疼痛的发生发展中发挥重要作用。我们研究了CGRP在三叉神经炎性疼痛中的作用，方法是检测CGRP的单抗对炎症的雪貂牙髓刺激反应时改变中枢Fos表达的能力。方法：在麻醉下制备10只成年雪貂，刺激左上、下部犬牙髓，记录二腹肌记录，并在随后的实验中静脉注射。在所有动物中，牙髓炎症都是通过将人类龋齿引入深颊腔而引起的。4天后静脉注射CGRP抗体(n=5)或赋形剂(n=5)。再麻醉2天后，以10倍张口反射阈值刺激牙髓。结果：Fos在同侧三叉神经尾侧亚核(Vc)和口侧亚核(Vo)均有表达。经降钙素基因相关肽抗体处理的动物Vc内Fos阳性核团明显减少(p=0.003与赋形剂处理组相比)。CD45的平均染色百分比面积在抗体处理的动物中显著减少(p=0.04与赋形剂处理的动物相比)。结论：这是第一个直接证据表明CGRP的隔离具有抗炎和可能的镇痛作用。此前使用这种Fos模型的研究已经证明，它能够预测临床止痛效果。因此，这些数据表明，该抗体可能在牙痛和其他类型的炎症介导的传播中具有止痛作用，并表明这部分是由于外周抗炎作用。(C)2012年IBRO。爱思唯尔有限公司出版。保留所有权利。
Background: Calcitonin gene-related peptide (CGRP) is a powerful pro-inflammatory mediator thought to play a significant role in the development of inflammation and pain. We investigated the role of CGRP in trigeminal inflammatory pain by determining the ability of a monoclonal antibody to CGRP to modify central Fos expression in response to stimulation of the inflamed ferret tooth pulp. We also assessed the effect of the antibody on pulpal inflammation.Methods: Ten adult ferrets were prepared under anaesthesia to allow stimulation of the upper and lower left canine pulps, recording from the digastric muscle and intravenous injections at subsequent experiments. In all animals, pulpal inflammation was induced by introducing human caries into a deep buccal cavity. Four days later animals were treated intravenously with either CGRP antibody (n = 5) or vehicle (n = 5). After a further 2 days animals were re-anaesthetised and the tooth pulps stimulated at 10 times jaw-opening reflex threshold. Brainstems and tooth pulps were processed immunohistochemically for Fos and the common leucocyte marker CD45, respectively.Results: Fos was expressed in ipsilateral trigeminal subnuclei caudalis (Vc) and oralis (Vo). Significantly fewer Fos-positive nuclei were present within Vc of CGRP antibody-treated animals (p = 0.003 vs vehicle-treated). Mean percentage area of staining for CD45 was significantly less in antibody-treated animals (p = 0.04 vs vehicle-treated).Conclusions: This is the first direct evidence that sequestration of CGRP has anti-inflammatory and putative analgesic effects. Previous studies using this Fos model have demonstrated that it is able to predict clinical analgesic efficacy. Thus these data indicate that this antibody may have analgesic effects in dental pain and other types of inflammatory-mediated transmission, and suggest that this is in part due to peripheral anti-inflammatory effects. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.