Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma.
Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma.
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DOI：
10.1097/j.pain.0000000000000103
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发表时间：
2015-04
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：
Li Z;Gu X;Sun L;Wu S;Liang L;Cao J;Lutz BM;Bekker A;Zhang W;Tao YX
周围神经损伤引起的背根神经节（DRG）初级感觉神经元基因转录和翻译的变化被认为有助于神经病理性疼痛的发生。转录因子控制基因表达。周围神经损伤增加髓样锌指蛋白1（MZF 1），一种转录因子的表达，并促进其与受损DRG中的电压门控钾1.2（Kv1.2）反义RNA基因的结合。然而，DRG MZF 1是否参与神经病理性疼痛仍是未知数。在这里，我们报告说，通过显微注射MZF1 siRNA到受损的DRG中，阻断神经损伤诱导的DRG MZF1的增加，减弱了坐骨神经慢性压迫性损伤（CCI）大鼠的机械、冷和热疼痛超敏反应的启动和维持，而不影响运动功能和对急性机械、热和冷刺激的基础反应。通过将表达全长MZF 1的重组腺相关病毒5显微注射到DRG中来模拟神经损伤诱导的DRG MZF 1增加，在未处理大鼠中产生显著的机械、冷和热疼痛超敏反应。从机制上讲，MZF 1参与了CCI诱导的Kv1.2 mRNA和蛋白以及总Kv电流的降低，以及CCI通过MZF 1触发的受损DRG神经元中Kv1.2反义RNA表达诱导的神经元兴奋性增加。MZF1可能是神经病理性疼痛的内源性触发因子，并可能作为预防和治疗这种疾病的潜在靶点。
Peripheral nerve injury-induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltage-gated potassium 1.2 (Kv1.2) antisense RNA gene in the injured DRG. However, whether DRG MZF1 participates in neuropathic pain is still unknown. Here, we report that blocking the nerve injury-induced increase of DRG MZF1 through microinjection of MZF1 siRNA into the injured DRG attenuated the initiation and maintenance of mechanical, cold, and thermal pain hypersensitivities in rats with chronic constriction injury (CCI) of the sciatic nerve, without affecting locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking the nerve injury-induced increase of DRG MZF1 through microinjection of recombinant adeno-associated virus 5 expressing full-length MZF1 into the DRG produced significant mechanical, cold, and thermal pain hypersensitivities in naïve rats. Mechanistically, MZF1 participated in CCI-induced reductions in Kv1.2 mRNA and protein and total Kv current and the CCI-induced increase in neuronal excitability through MZF1-triggered Kv1.2 antisense RNA expression in the injured DRG neurons. MZF1 is likely an endogenous trigger of neuropathic pain and might serve as a potential target for preventing and treating this disorder.
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影响因子：
3.3
作者：
Fan L;Guan X;Wang W;Zhao JY;Zhang H;Tiwari V;Hoffman PN;Li M;Tao YX
通讯作者：
Tao YX
影响因子：
82.9
作者：
Kawasaki, Yasuhiko;Xu, Zhen-Zhong;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong
影响因子：
3.6
作者：
Castle, NA;London, DO;Sabatier, JM
通讯作者：
Sabatier, JM
影响因子：
1.7
作者：
Kerr, BJ;Souslova, V;Wood, JN
通讯作者：
Wood, JN
影响因子：
3.3
作者：
Nassar MA;Levato A;Stirling LC;Wood JN
通讯作者：
Wood JN