Activation of p38 and p42/44 MAP kinase in neuropathic pain:: Involvement of VPAC2 and NK2 receptors and mediation by spinal glia
Activation of p38 and p42/44 MAP kinase in neuropathic pain:: Involvement of VPAC2 and NK2 receptors and mediation by spinal glia
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DOI：
10.1016/j.mcn.2005.08.016
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发表时间：
2005-12-01
影响因子：
3.5
通讯作者：
Fleetwood-Walker, SM
中科院分区：
文献类型：
--
作者：
Garry, EM;Delaney, A;Fleetwood-Walker, SM
涉及p38和p42/44 MAP激酶的细胞内信号通路的激活可能对脊髓神经元致敏背后的突触可塑性起重要作用。p38或p42/44通路抑制剂可适度减弱芥菜油而非刷子引起的背角神经元反应，并减轻神经损伤后的行为反射敏化。NMDA、VPAC(2)和NK2（但不相关）受体拮抗剂、神经胶质抑制剂丙烯茶碱和tnf - α抑制剂可降低与收缩损伤同侧脊髓中p38和p42/44 MAP激酶的激活。一种VPAC2受体激动剂增强了p38磷酸化，并在幼稚动物中引起行为反射致敏，这种致敏可以通过联合给药p38抑制剂来阻断。相反，NK2受体激动剂激活p42/44并引起行为致敏，可通过联合给药p42/44抑制剂来预防。因此，脊髓p38和p42/44 MAP激酶在神经性疼痛状态下被激活，其机制涉及VPAC(2)、NK2、NMDA受体和胶质细胞因子的产生。(c) 2005爱思唯尔公司版权所有。
Activation of intracellular signaling pathways involving p38 and p42/44 MAP kinases may contribute importantly to synaptic plasticity underlying spinal neuronal sensitization. Inhibitors of p38 or p42/44 pathways moderately attenuated responses of dorsal horn neurons evoked by mustard oil but not brush and alleviated the behavioral reflex sensitization seen following nerve injury. Activation of p38 and p42/44 MAP kinases in spinal cord ipsilateral to constriction injury was reduced by antagonists of NMDA, VPAC(2) and NK2 (but not related) receptors, the glial inhibitor propentofylline and inhibitors of TNF-alpha. A VPAC2 receptor agonist enhanced p38 phosphorylation and caused behavioral reflex sensitization in naive animals that could be blocked by co-administration of p38 inhibitor. Conversely, an NK2 receptor agonist activated p42/44 and caused behavioral sensitization that could be prevented by co-administration of p42/44 inhibitor. Thus, spinal p38 and p42/44 MAP kinases are activated in neuropathic pain states by mechanisms involving VPAC(2), NK2, NMDA receptors and gliail cytokine production. (c) 2005 Elsevier Inc. All rights reserved.