Reversal of TRESK Downregulation Alleviates Neuropathic Pain by Inhibiting Activation of Gliocytes in the Spinal Cord
Reversal of TRESK Downregulation Alleviates Neuropathic Pain by Inhibiting Activation of Gliocytes in the Spinal Cord
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DOI：
10.1007/s11064-016-2170-z
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发表时间：
2017-02
影响因子：
4.4
通讯作者：
Jun Zhou;Hongtao Chen;Cheng-xiang Yang;J. Zhong;Wan-You He;Q. Xiong
中科院分区：
文献类型：
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作者：
Jun Zhou;Hongtao Chen;Cheng-xiang Yang;J. Zhong;Wan-You He;Q. Xiong
尽管人们一致认为twik相关脊髓K+(TRESK)的激活可能与慢性疼痛的发病机制有关，但疼痛信号转移和发展的具体机制仍不清楚。在本研究中，我们证实了TRESK在神经元中而不是在胶质细胞中表达。此外，在神经性疼痛（NP）的SNI模型中，脊髓神经元中TRESK的下调导致连接蛋白36 （Cx36）和连接蛋白43 （Cx43）的上调，两者都是脊髓间隙连接的亚型，最终脊髓胶质细胞被激活。与SNI大鼠相比，鞘内注射TRESK基因重组腺病毒可显著下调Cx36和Cx43的表达水平，抑制脊髓胶质细胞的活化，痛感明显减轻。综上所述，TRESK通过上调突触传递和激活胶质细胞参与NP的发病机制。
Despite the consensus that activation of TWIK-related spinal cord K+(TRESK) might contribute to the pathogenesis of chronic pain, the specific mechanisms underlying the transfer and development of pain signals still remain obscure. In the present study, we validated that TRESK was expressed in neurons instead of glial cells. Furthermore, in the SNI model of neuropathic pain (NP), downregulation of TRESK in spinal cord neurons resulted in upregulation of connexin 36 (Cx36) and connexin 43 (Cx43), both being subtypes of gap junctions in the spinal cord, with gliocytes in the spinal cord activated ultimately. Compared with SNI rats, intrathecal injection of TRESK gene recombinant adenovirus significantly downregulated the expression levels of Cx36 and Cx43 and suppressed the activation of gliocytes in the spinal cord, with hyperalgesia significantly reduced. In conclusion, TRESK contributes to the pathogenesis of NP by upregulation of synaptic transmission and activation of gliocytes.