Ketamine Depresses Toll-Like Receptor 3 Signaling in Spinal Microglia in a Rat Model of Neuropathic Pain
Ketamine Depresses Toll-Like Receptor 3 Signaling in Spinal Microglia in a Rat Model of Neuropathic Pain
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氯胺酮抑制神经性疼痛大鼠模型脊髓小胶质细胞中 Toll 样受体 3 信号传导
DOI：
10.1159/000324293
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Li, Yun-Qing
中科院分区：
文献类型：
--
作者：
Mei, Xiao-Peng;Zhou, Yang;Wang, Wei;Tang, Jun;Wang, Wen;Zhang, Hui;Xu, Li-Xian;Li, Yun-Qing
研究表明，小胶质细胞在脊髓神经结扎（SNL）引起的神经性疼痛中起关键作用，toll样受体3 （TLR3）在脊髓小胶质细胞的激活和神经损伤后触觉异常性痛的发生中起重要作用。此外，氯胺酮可以抑制体外小胶质细胞的激活，氯胺酮可能通过抑制tlr介导的信号转导来抑制促炎基因的表达。因此，本研究旨在揭示鞘内氯胺酮是否能抑制snl诱导的脊髓小胶质细胞激活，并通过抑制TLR3激活对神经性疼痛起到一定的抗异动作用。行为学结果显示鞘内氯胺酮以剂量依赖的方式减轻snl诱导的机械性异常痛以及脊髓小胶质细胞激活。此外，Western blot分析显示，氯胺酮可下调snl诱导的磷酸化p38 （p-p38）表达，该蛋白在脊髓小胶质细胞中特异性表达，而在星形胶质细胞和神经元中不表达。此外，氯胺酮可以逆转TLR3激动剂（多肌苷-多胞酸）诱导的机械性异痛和脊髓小胶质细胞活化。综上所示，鞘内氯胺酮抑制tlr3诱导的脊髓小胶质p-p38丝裂原活化蛋白激酶通路的激活，可能是氯胺酮对SNL诱导的神经性疼痛具有抗异动作用的原因之一。
Reports suggest that microglia play a key role in spinal nerve ligation (SNL)-induced neuropathic pain, and toll-like receptor 3 (TLR3) has a substantial role in the activation of spinal microglia and the development of tactile allodynia after nerve injury. In addition, ketamine application could suppress microglial activation in vitro, and ketamine could inhibit proinflammatory gene expression possibly by suppressing TLR-mediated signal transduction. Therefore, the present study was designed to disclose whether intrathecal ketamine could suppress SNL-induced spinal microglial activation and exert some antiallodynic effects on neuropathic pain by suppressing TLR3 activation. Behavioral results showed that intrathecal ketamine attenuated SNL-induced mechanical allodynia, as well as spinal microglial activation, in a dose-dependent manner. Furthermore, Western blot analysis displayed that ketamine application downregulated SNL-induced phosphorylated-p38 (p-p38) expression, which was specifically expressed in spinal microglia but not in astrocytes or neurons. Besides, ketamine could reverse TLR3 agonist (polyinosine-polycytidylic acid)-induced mechanical allodynia and spinal microglia activation. It was concluded that intrathecal ketamine depresses TLR3-induced spinal microglial p-p38 mitogen-activated protein kinase pathway activation after SNL, probably contributing to the antiallodynic effect of ketamine on SNL-induced neuropathic pain.
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影响因子：
6.2
作者：
Bettoni, Isabella;Comelli, Francesca;Costa, Barbara
通讯作者：
Costa, Barbara
影响因子：
9.8
作者：
Nadeson, R;Tucker, A;Goodchild, CS
通讯作者：
Goodchild, CS
DOI：
--
发表时间：
2005
期刊：
--
影响因子：
--
作者：
通讯作者：
--
影响因子：
1.9
作者：
Min Yu;Dan-bing Shao;Jianjun Yang;S. Feng;Jianguo Xu
通讯作者：
Min Yu;Dan-bing Shao;Jianjun Yang;S. Feng;Jianguo Xu
影响因子：
5.3
作者：
Hevers, Wulf;Hadley, Stephen H.;Amin, Jahanshah
通讯作者：
Amin, Jahanshah