Activation of Src Family Kinases in Spinal Microglia Contributes to Formalin-Induced Persistent Pain State Through p38 Pathway
Activation of Src Family Kinases in Spinal Microglia Contributes to Formalin-Induced Persistent Pain State Through p38 Pathway
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脊髓小胶质细胞中 Src 家族激酶的激活通过 p38 通路导致福尔马林诱导的持续性疼痛状态
DOI：
10.1016/j.jpain.2012.07.010
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发表时间：
2012-10-01
期刊：
影响因子：
4
通讯作者：
Fu, Kai-Yuan
中科院分区：
文献类型：
--
作者：
Tan, Yong-Hui;Li, Kai;Fu, Kai-Yuan
蛋白质酪氨酸磷酸化与正常和病理功能如细胞增殖、迁移和分化有关。最近的研究表明，Src家族激酶（SFKs）参与神经系统疾病和神经病理性疼痛状态，其中小胶质细胞活化起作用。在福尔马林试验中，我们已经报道了小胶质细胞至少经历了2个不同的活化阶段，其基于关于p38丝裂原活化蛋白激酶（MAPK）的信号事件。在这里，我们研究了SFKs信号转导在福尔马林疼痛动物模型中的参与以及与p38 MAPK的关联。结果表明，脊髓小胶质细胞SFKs在福尔马林注射后第1天开始激活，持续7天。SFK特异性抑制剂PP 2预处理不能抑制福尔马林诱导的自发痛行为。然而，PP 2抑制福尔马林损伤，诱导持续的机械性痛觉过敏，并逆转小胶质细胞磷酸化p38的表达，以及在注射后第3天和第7天使用的Westernblot染色。我们的研究结果表明，脊髓小胶质细胞中的Src/p38 MAPK信号级联的激活有助于后期的持续性机械痛觉过敏引起福尔马林注射到paw.Perspective：这项研究提出了独特的属性，脊髓小胶质细胞激活疼痛动物模型。这一发现可能有助于临床医生进一步了解脊髓小胶质细胞对急性和持续性疼痛状态的贡献。(C)2012年，美国疼痛协会。爱思唯尔公司出版版权所有
Protein tyrosine phosphorylation has been implicated in normal and pathological functions such as cell proliferation, migration and differentiation. Recently, some studies have shown that Src family kinases (SFKs) were involved in neurological disorders and neuropathic pain states in which microglial activation plays a role. In the formalin test, we have reported that microglia undergo at least 2 distinct stages of activation on the basis of signaling events regarding p38 mitogen-activated protein kinases (MAPK). Here, we investigated the involvement of SFKs signaling in a formalin pain animal model and the association with p38 MAPK. Our results showed that SFKs were activated in the spinal microglia beginning 1 day after peripheral formalin injection lasting for 7 days. Pretreatment with SFK specific inhibitor PP2 could not inhibit formalin-induced spontaneous pain behaviors. However, PP2 inhibited formalin injury, induced persistent mechanical hyperalgesia, and reversed microglial phospho-p38 expression as well using immunohistostaining and Western blot at day 3 and 7 after injection. Our results suggested that the activation of the Src/p38MAPK signaling cascade in spinal microglia contributed to late stage persistent mechanical hyperalgesia evoked by formalin injection into the paw.Perspective: This study presents unique properties of spinal micro glial activation in a pain animal model. This finding could potentially help clinicians to further understand the contributions of spinal micro glia to acute and persistent pain state. (C) 2012 by the American Pain Society. Published by Elsevier Inc. All rights reserved