Nogo-A Induced Polymerization of Microtubule Is Involved in the Inflammatory Heat Hyperalgesia in Rat Dorsal Root Ganglion Neurons.
Nogo-A Induced Polymerization of Microtubule Is Involved in the Inflammatory Heat Hyperalgesia in Rat Dorsal Root Ganglion Neurons.
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nogos - a诱导的微管聚合参与了大鼠背根神经节神经元的炎症性热痛觉过敏。
DOI：
10.3390/ijms221910360
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发表时间：
2021-09-26
影响因子：
5.6
通讯作者：
Wang J
中科院分区：
文献类型：
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作者：
Chen L;Hu Q;Liu H;Zhao Y;Chan SO;Wang J
微管是细胞骨架的主要组成部分，被证明与瞬时受体潜在香草素亚家族成员1（TRPV 1）结合并相互作用，并在炎症性疼痛中产生热痛敏中发挥关键作用。Nogo-A是微管组装的调节剂，在维持TRPV 1在炎性热痛中的功能中起关键作用。然而，背根神经节（DRG）神经元中Nogo-A调控的微管动力学是否参与了炎性疼痛尚不清楚。本文报道了完全弗氏佐剂（CFA）诱导的炎性痛时，DRG神经元内微管聚合（如乙酰化α-微管蛋白、微管蛋白聚合促进蛋白3（TPPP 3）和微管数量）显著增加。与我们先前的结果一致，敲除（KO）Nogo-A蛋白显著减轻CFA注射后72 h的热痛觉过敏，并通过上调DRG中的神经元蛋白反应介导蛋白2（CRMP 2）的磷酸化来减少微管聚合。在炎症疼痛的Nogo-A KO大鼠中，乙酰化α-微管蛋白和TRPV 1在背根节神经元中的共定位也显着减少。此外，鞘内注射紫杉醇（一种微管稳定剂）可逆转注射CFA后Nogo-A KO大鼠DRG中TRPV 1的下调。此外，鞘内注射诺考达唑（微管破坏剂）显着减弱CFA诱导的炎性热痛觉过敏和机械性疼痛的大鼠模型的备用神经损伤（SNI）。在这些SNI病例中，DRG中的Nogo-A和乙酰化α-微管蛋白也显著上调。我们的结论是Nogo-A促进的DRG中微管的聚合有助于TRPV 1介导的炎性热痛觉过敏的发展。
The microtubule, a major constituent of cytoskeletons, was shown to bind and interact with transient receptor potential vanilloid subfamily member 1 (TRPV1), and serves a pivotal role to produce thermal hyperalgesia in inflammatory pain. Nogo-A is a modulator of microtubule assembly and plays a key role in maintaining the function of TRPV1 in inflammatory heat pain. However, whether the microtubule dynamics modulated by Nogo-A in dorsal root ganglion (DRG) neurons participate in the inflammatory pain is not elucidated. Here we reported that the polymerization of microtubules in the DRG neurons, as indicated by the acetylated α-tubulin, tubulin polymerization-promoting protein 3 (TPPP3), and microtubule numbers, was significantly elevated in the complete Freund’s adjuvant (CFA) induced inflammatory pain. Consistent with our previous results, knock-out (KO) of Nogo-A protein significantly attenuated the heat hyperalgesia 72 h after CFA injection and decreased the microtubule polymerization via up-regulation of phosphorylation of collapsin response mediator protein 2 (CRMP2) in DRG. The colocalization of acetylated α-tubulin and TRPV1 in DRG neurons was also reduced dramatically in Nogo-A KO rats under inflammatory pain. Moreover, the down-regulation of TRPV1 in DRG of Nogo-A KO rats after injection of CFA was reversed by intrathecal injection of paclitaxel, a microtubule stabilizer. Furthermore, intrathecal injection of nocodazole (a microtubule disruptor) attenuated significantly the CFA-induced inflammatory heat hyperalgesia and the mechanical pain in a rat model of spared nerve injury (SNI). In these SNI cases, the Nogo-A and acetylated α-tubulin in DRG were also significantly up-regulated. We conclude that the polymerization of microtubules promoted by Nogo-A in DRG contributes to the development of inflammatory heat hyperalgesia mediated by TRPV1.
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影响因子：
5.3
作者：
Chuckowree JA;Zhu Z;Brizuela M;Lee KM;Blizzard CA;Dickson TC
通讯作者：
Dickson TC
Nogo-A 通过维持大鼠背根神经节神经元中的 TRPV1 功能促进炎症热痛觉过敏
影响因子：
4.8
作者：
Hu, Fang;Liu, Huai-Cun;Wang, Jun
通讯作者：
Wang, Jun
影响因子：
7.7
作者：
Morley, Shane J.;Qi, Yanmei;Heppenstall, Paul A.
通讯作者：
Heppenstall, Paul A.
影响因子：
21.3
作者：
Fukata, Y;Itoh, TJ;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
64.8
作者：
通讯作者：
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