Activation of spinal extracellular signaling-regulated kinases by intraplantar melittin injection
Activation of spinal extracellular signaling-regulated kinases by intraplantar melittin injection
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DOI：
10.1016/j.neulet.2005.02.033
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发表时间：
2005-06-10
影响因子：
2.5
通讯作者：
Chen, J
中科院分区：
文献类型：
--
作者：
Yu, YQ;Chen, J
足底注射蜂毒肽（全蜂毒的一种主要毒性肽）已被证明会引起大鼠行为和脊髓神经元反应的改变。为了了解脊髓背角中的细胞外信号调节激酶 (ERK) 是否被激活并参与诱导和维持持续性伤害感受、疼痛超敏反应和炎症，通过长期鞘内注射三种剂量的 U0126（1,4-二氨基-2,3-二氰基-1, 4-双-[邻氨基苯硫基]丁二烯），一种广泛使用的特异性 MAP 激酶激酶 (MEK) 抑制剂。在足底注射蜂毒肽之前或之后插入导管。我们发现：（1）U0126可以以剂量相关的方式抑制蜂毒肽诱导的持续性自发性伤害感受（PSN）、机械和热超敏反应； (2)特异性抑制ERK通路可抑制蜂毒肽诱导的PSN和热超敏反应的维持，而已建立的机械超敏反应无法逆转；(3)鞘内注射U0126对蜂毒肽诱导的外周炎症没有影响。这一结果表明脊髓ERK通路可能是诱导和维持持续性疼痛和热痛觉过敏的病理生理过程的共同因素，而ERK通路在机械超敏反应产生中的作用并不一致，有待进一步阐明。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
Intraplantar injection of melittin, a major toxic peptide of whole bee venom, has been proved to cause alteration in both behavioral and spinal neuronal responses in rats. To see whether extracellular signaling-regulated kinases (ERK) in the spinal cord dorsal horn are activated and involved in induction and maintenance of persistent ongoing nociception, pain hypersensitivity and inflammation, three doses of U0126 (1,4-diamino-2,3-dicyano-1, 4-bis-[o-aminophenylmercapto]butadiene), a widely used specific MAP kinase kinase (MEK) inhibitor, were administered through chronic intrathecal catheterization prior to or after intraplantar injection of melittin. We found that: (1) the induction of melittin-induced persistent spontaneous nociception (PSN), mechanical and heat hypersensitivity could be suppressed by U0126 in a dose-related manner; (2) specific inhibition of ERK pathway suppressed the maintenance of melittin-induced PSN and heat hypersensitivity, while established mechanical hypersensitivity could not be reversed, and (3) intrathecal administration of U0126 had no effects on peripheral inflammation induced by melittin. This result suggests that spinal ERK pathway might be a common factor involved in inducing and maintaining pathophysiological processes of ongoing pain and heat hyperalgesia, while the role of ERK pathway in generation of the mechanical hypersensitivity is not consistent and remains to be further clarified. (c) 2005 Elsevier Ireland Ltd. All rights reserved.