title: Protein kinase B/Akt is required for complete Freund's adjuvant-induced upregulation of Nav1.7 and Nav1.8 in primary sensory neurons.
abstract: 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 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Lingli
authors: L
authors: Liang
authors: Longchang
authors: L
authors: Fan
authors: Bo
authors: B
authors: Tao
authors: Myron
authors: M
authors: Yaster
authors: Yuan-Xiang
authors: YX
authors: Tao
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000378:metabolism*; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568319:Scn10a protein, rat; C503480:Scn9a protein, rat; D005620:Freund's Adjuvant; D051058:Oncogene Protein v-akt; D051057:Proto-Oncogene Proteins c-akt; D010751:Phosphopyruvate Hydratase
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