Activation of peripheral ephrinBs/EphBs signaling induces hyperalgesia through a MAPKs-mediated mechanism in mice
Activation of peripheral ephrinBs/EphBs signaling induces hyperalgesia through a MAPKs-mediated mechanism in mice
复制标题
外周 ephrinBs/EphBs 信号的激活通过 MAPKs 介导的机制诱导小鼠痛觉过敏
DOI：
10.1016/j.pain.2008.06.023
复制
发表时间：
2008-10-31
期刊：
影响因子：
7.4
通讯作者：
Zeng, Yin-Ming
中科院分区：
文献类型：
--
作者：
Cao, Jun-Li;Ruan, Jia-Ping;Zeng, Yin-Ming
EphBs受体和ephrinBs配体存在于成人脑和外周组织中，并在调节生理学和病理生理学的多个方面中发挥关键作用。我们的研究和其他研究表明脊髓ephrinBs/EphBs信号通路参与了伤害性信息的调节和中枢敏化。然而，ephrinBs/EphBs信号传导在外周致敏中的作用知之甚少。这项研究表明，足底（i.pl.）注射ephrinBI-Fc在小鼠中产生剂量和时间依赖性热和机械痛觉过敏以及脊髓Fos蛋白表达的增加，这可以通过用EphBl-Fc预处理来部分预防。EphrinBl-Fc诱导的痛觉过敏伴随着NMDA受体介导的外周和脊髓磷酸化促分裂原活化蛋白激酶（磷酸-MAPK）（包括p-p38、pERK和pJNK）的表达增加，并且还通过外周和脊髓MAPK的抑制来预防或逆转。此外，在福尔马林炎症疼痛模型中，通过注射EphBI-Fc对EphBs受体的预抑制降低了疼痛行为，这伴随着外周p-p38、pERK和pJNK表达的降低。这些数据提供了证据表明ephrinBs可能作为外周致敏的突出贡献者，并证明外周ephrinBs/EphBs系统的激活通过MAPK介导的机制诱导痛觉过敏。(C)2008年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
EphBs receptors and ephrinBs ligands are present in the adult brain and peripheral tissue and play a critical role in modulating multiple aspects of physiology and pathophysiology. Ours and other Studies have demonstrated that spinal ephrinBs/EphBs signaling was involved in the modulation of nociceptive information and central sensitization. However, the role of ephrinBs/EphBs signaling in peripheral sensitization is poorly understood. This study shows that intraplantar (i.pl.) injection of ephrinBI-Fc produces a dose- and time-dependent thermal and mechanical hyperalgesia and the increase of spinal Fos protein expression in mice, which can be partially prevented by pre-treatment with EphBl-Fc. EphrinBl-Fc-induced hyperalgesia is accompanied with the NMDA receptor-mediated increase of expression in peripheral and spinal phosphorylated mitogen-activated protein kinases (phospho-MAPKs) including p-p38, pERK and pJNK, and also is prevented or reversed by the inhibition of peripheral and spinal MAPKs. Furthermore, in formalin inflammation pain model, pre-inhibition of EphBs receptors by the injection of EphBI-Fc reduces pain behavior, which is accompanied by the decreased expression of peripheral p-p38, pERK and pJNK. These data provide evidence that ephrinBs may act as a prominent contributor to peripheral sensitization, and demonstrate that activation of peripheral ephrinBs/EphBs system induces hyperalgesia through a MAPKs-mediated mechanism. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.