Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury.
Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury.
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背根神经节八聚体转录因子1对周围神经损伤后神经病理性疼痛的作用。
DOI：
10.1097/j.pain.0000000000001405
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发表时间：
2019-03
期刊：
影响因子：
7.4
通讯作者：
Tao YX
中科院分区：
文献类型：
--
作者：
Yuan J;Wen J;Wu S;Mao Y;Mo K;Li Z;Su S;Gu H;Ai Y;Bekker A;Zhang W;Tao YX
神经病理性疼痛的发生与周围神经损伤后背根神经节（DRG）的基因改变有关。转录因子控制基因表达。在这项研究中，我们调查是否八聚体转录因子1（OCT 1），转录因子，促成了坐骨神经慢性压迫性损伤（CCI）引起的神经病理性疼痛。CCI在同侧L4/5 DRG中产生了OCT 1蛋白水平的时间依赖性增加，但在脊髓中没有。通过向同侧L4/5 DRG中显微注射OCT 1 siRNA阻断这种增加减弱了CCI诱导的机械异常性疼痛、热痛觉过敏和冷异常性疼痛的起始和维持，并改善了CCI后的吗啡镇痛，而不影响对急性机械、热和冷刺激的基础反应以及运动功能。通过显微注射携带全长OCT 1的重组腺相关病毒5到单侧L4/5 DRG中来模拟这种增加，导致幼稚大鼠中显著的机械异常性疼痛、热痛觉过敏和冷异常性疼痛。在损伤的DRG中，OCT 1参与了CCI诱导的Dnmt 3a mRNA及其蛋白的增加以及DNMT 3a介导的Oprm 1和Kcna 2 mRNA及其蛋白的减少。这些研究结果表明，OCT 1可能参与神经性疼痛至少部分通过转录激活Dnmt 3a和随后的表观遗传沉默的Oprm 1和Kcan 2在DRG中。OCT 1可作为神经病理性疼痛治疗的潜在靶点。
Neuropathic pain genesis is related to gene alterations in the dorsal root ganglion (DRG) following peripheral nerve injury. Transcription factors control gene expression. In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. CCI produced a time-dependent increase in the level of OCT1 protein in the ipsilateral L4/5 DRG, but not in the spinal cord. Blocking this increase through microinjection of OCT1 siRNA into the ipsilateral L4/5 DRG attenuated the initiation and maintenance of CCI-induced mechanical allodynia, heat hyperalgesia, and cold allodynia and improved morphine analgesia after CCI, without affecting basal responses to acute mechanical, heat, and cold stimuli as well as locomotor functions. Mimicking this increase through microinjection of recombinant adeno-associated virus 5 harboring full-length OCT1 into the unilateral L4/5 DRG led to marked mechanical allodynia, heat hyperalgesia and cold allodynia in naive rats. Mechanistically, OCT1 participated in CCI-induced increases in Dnmt3a mRNA and its protein and DNMT3a-mediated decreases in Oprm1 and Kcna2 mRNAs and their proteins in the injured DRG. These findings indicate that OCT1 may participate in neuropathic pain at least in part by transcriptionally activating Dnmt3a and subsequently epigenetic silencing of Oprm1 and Kcan2 in the DRG. OCT1 may serve as a potential target for therapeutic treatments against neuropathic pain.
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影响因子：
2.9
作者：
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通讯作者：
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作者：
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DOI：
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发表时间：
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作者：
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通讯作者：
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作者：
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