Acute inhibition of Ca2+/calmodulin-dependent protein kinase II reverses experimental neuropathic pain in mice
Language: 
English
Abstract: 

The limited data that currently exist for the role of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in neuropathic pain are conflicting. In the present study, we tested the hypothesis that CaMKII is required for the maintenance of neuropathic pain in a rodent model of experimental mononeuropathy. Spinal nerve L(5)/L(6) ligation (SNL) was found to increase the spinal activity of CaMKII (pCaMKII) on the ipsilateral (but not contralateral) side. This effect was blocked by 2-[N-(2-hydroxyethyl)-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) (KN93) (intrathecal injection), a CaMKII inhibitor. Acute treatment with KN93 dose-dependently reversed SNL-induced thermal hyperalgesia and mechanical allodynia. The action of KN93 lasted for at least 2 to 4 h. 2-[N-(4-Methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine (KN92) (45 nmol i.t.), an inactive analog of KN93, showed no effect on SNL-induced CaMKII activation, allodynia, or hyperalgesia. We further examined the pharmacologic action of trifluoperazine, a clinically used antipsychotic drug that we found to be a potent CaMKII inhibitor in these assays. Trifluoperazine (administered intraperitoneally or by mouth) dose-dependently reversed SNL-induced mechanical allodynia, thermal hyperalgesia, and CaMKII activation without causing locomotor impairment in mice at the highest doses used. In conclusion, our findings support a critical role of CaMKII in neuropathic pain. Blocking CaMKII or CaMKII-mediated signaling may offer a novel therapeutic target for the treatment of neuropathic pain.

Author(s): 
Chen, Yan
Luo, Fang
Yang, Cheng
Kirkmire, Chelsea M.
Wang, Zaijie Jim
Item Type: 
Journal Article
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics
Journal Abbreviation: 
J. Pharmacol. Exp. Ther.
Publication Date: 
Aug 2009
Publication Year: 
2009
Pages: 
650-659
Volume: 
330
Issue: 
2
ISSN: 
1521-0103
DOI: 
10.1124/jpet.109.152165
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 19478130 PMCID: PMC2713096

Turabian/Chicago Citation

Yan Chen, Fang Luo, Cheng Yang, Chelsea M. Kirkmire and Zaijie Jim Wang. Aug 2009. "Acute inhibition of Ca2+/calmodulin-dependent protein kinase II reverses experimental neuropathic pain in mice." The Journal of Pharmacology and Experimental Therapeutics 330: 2: 650-659. 10.1124/jpet.109.152165.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1124/jpet.109.152165 | issn = 1521-0103 | volume = 330 | pages = 650-659 | last = Chen | first = Yan | coauthors = Luo, Fang, Yang, Cheng, Kirkmire, Chelsea M., Wang, Zaijie Jim | title = Acute inhibition of Ca2+/calmodulin-dependent protein kinase II reverses experimental neuropathic pain in mice | journal = The Journal of Pharmacology and Experimental Therapeutics | date = Aug 2009 | pmid = | pmc = }} </ref>