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.
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.
Key words
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Article info
Publication history
Published online: May 02, 2013
Accepted:
January 25,
2013
Received in revised form:
December 18,
2012
Received:
August 11,
2012
Footnotes
Supported by grants (NS072206, NS058886, DA033390) from the National Institutes of Health; Mr. David Koch and the Patrick C. Walsh Prostate Cancer Research Fund; the Rita Allen Foundation; and the Blaustein Pain Research Fund.
The authors do not have any conflicts of interest.
Identification
Copyright
© 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.
