Protein kinase B/Akt is required for complete Freund's adjuvant-induced upregulation of Nav1.7 and Nav1.8 in primary sensory neurons.
Protein kinase B/Akt is required for complete Freund's adjuvant-induced upregulation of Nav1.7 and Nav1.8 in primary sensory neurons.
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DOI：
10.1016/j.jpain.2013.01.778
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发表时间：
2013-06
期刊：
影响因子：
4
通讯作者：
Tao, Yuan-Xiang
中科院分区：
文献类型：
--
作者：
Liang, Lingli;Fan, Longchang;Tao, Bo;Yaster, Myron;Tao, Yuan-Xiang
电压门控钠通道（Nav）对于动作电位的产生和传导是必不可少的。外周炎症增加了背根神经节（DRG）神经元Nav1.7和Nav1.8的表达，提示它们参与了慢性炎症痛的诱导和维持。然而，Nav1.7和Nav1.8在炎性疼痛条件下如何在DRG中调节仍不清楚。采用完全弗氏佐剂（CFA）诱导的慢性炎性疼痛模型和Western blot分析，我们发现在足底注射CFA后第3天和第7天，大鼠同侧L4/5背根神经节磷酸化Akt（p-Akt）显著增加。免疫组化结果显示，在同侧L4/5背根节中p-Akt阳性神经元的百分比也显著增加。此外，CFA注射增加了L4/5 DRG神经元中p-Akt与Nav1.7和Nav1.8的共定位。鞘内注射Akt抑制剂IV预处理大鼠，在CFA注射后第7天阻断CFA诱导的热痛觉过敏和CFA诱导的L4/5 DRG中Nav1.7和Nav1.8的增加。我们的研究结果表明，Akt通路参与了炎症诱导的DRG神经元Nav1.7和Nav1.8表达上调。这种参与可能有助于维持慢性炎性疼痛。这篇文章提出，抑制Akt阻断CFA诱导的热痛觉过敏和CFA诱导的背根神经节Nav1.7和Nav1.8的增加。这些发现对使用Akt抑制剂预防和/或治疗持续性炎性疼痛具有潜在意义。
Voltage-gated sodium channels (Nav) are essential for the generation and conduction of action potentials. Peripheral inflammation increases the expression of Nav1.7 and Nav1.8 in dorsal root ganglion (DRG) neurons, suggesting that they participate in the induction and maintenance of chronic inflammatory pain. However, how Nav1.7 and Nav1.8 are regulated in the DRG under inflammatory pain conditions remains unclear. Using a complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain model and Western blot analysis, we found that phosphorylated Akt (p-Akt) was significantly increased in the ipsilateral L4/5 DRGs of rats on days 3 and 7 after intraplantar CFA injection. Immunohistochemistry showed that the percentage of p-Akt-positive neurons in the DRG was also significantly increased in the ipsilateral L4/5 DRGs at these times. Moreover, CFA injection increased the colocalization of p-Akt with Nav1.7 and Nav1.8 in L4/5 DRG neurons. Pretreatment of rats with an intrathecal injection of Akt inhibitor IV blocked CFA-induced thermal hyperalgesia and CFA-induced increases in Nav1.7 and Nav1.8 in the L4/5 DRGs on day 7 after CFA injection. Our findings suggest that the Akt pathway participates in inflammation-induced upregulation of Nav1.7 and Nav1.8 expression in DRG neurons. This participation might contribute to the maintenance of chronic inflammatory pain. This article presents that inhibition of Akt blocks CFA-induced thermal hyperalgesia and CFA-induced increases in dorsal root ganglion Nav1.7 and Nav1.8. These findings have potential implications for use of Akt inhibitors to prevent and/or treat persistent inflammatory pain.
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影响因子：
3.3
作者：
Park JS;Yaster M;Guan X;Xu JT;Shih MH;Guan Y;Raja SN;Tao YX
通讯作者：
Tao YX
影响因子：
7.4
作者：
Gao YJ;Xu ZZ;Liu YC;Wen YR;Decosterd I;Ji RR
通讯作者：
Ji RR
影响因子：
5.3
作者：
Price, Theodore J.;Rashid, Md Harunor;Cervero, Fernando
通讯作者：
Cervero, Fernando
影响因子：
3.3
作者：
Asante, Curtis O.;Wallace, Victoria C.;Dickenson, Anthony H.
通讯作者：
Dickenson, Anthony H.
影响因子：
3.4
作者：
Pezet, S;Spyropoulos, A;McMahon, SB
通讯作者：
McMahon, SB