Voltage-gated sodium channels (Nay) 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 time points. 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. Perspective: 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. (C) 2013 by the American Pain Society
基金：
National Institutes of Health [NS072206, NS058886, DA033390]; Mr. David Koch and the Patrick C. Walsh Prostate Cancer Research Fund; Rita Allen Foundation; Blaustein Pain Research Fund
第一作者单位：[1]Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA
通讯作者：
通讯机构：[1]Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA[*1]Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, 1721 East Madison St,370 Ross, Baltimore, MD 21205 USA
推荐引用方式(GB/T 7714)：
Liang Lingli,Fan Longchang,Tao Bo,et al.Protein Kinase B/Akt Is Required for Complete Freund's Adjuvant-Induced Upregulation of Nav1.7 and Nav1.8 in Primary Sensory Neurons[J].JOURNAL OF PAIN.2013,14(6):638-647.doi:10.1016/j.jpain.2013.01.778.
APA：
Liang, Lingli,Fan, Longchang,Tao, Bo,Yaster, Myron&Tao, Yuan-Xiang.(2013).Protein Kinase B/Akt Is Required for Complete Freund's Adjuvant-Induced Upregulation of Nav1.7 and Nav1.8 in Primary Sensory Neurons.JOURNAL OF PAIN,14,(6)
MLA：
Liang, Lingli,et al."Protein Kinase B/Akt Is Required for Complete Freund's Adjuvant-Induced Upregulation of Nav1.7 and Nav1.8 in Primary Sensory Neurons".JOURNAL OF PAIN 14..6(2013):638-647
