Reversal of chronic inflammatory pain by acute inhibition of Ca2+/calmodulin-dependent protein kinase II

The Journal of Pharmacology and Experimental Therapeutics
Fang LuoZaijie J Wang

Abstract

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a major protein kinase that is capable of regulating the activities of many ion channels and receptors. In the present study, the role of CaMKII in the complete Freund's adjuvant (CFA)-induced inflammatory pain was investigated. Intraplantarly injected CFA was found to induce spinal activity of CaMKII (phosphorylated CaMKII), which was blocked by KN93 [[2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine)], a CaMKII inhibitor. Pretreatment with KN93 (i.t.) dose-dependently prevented the development of CFA-induced thermal hyperalgesia and mechanical allodynia. Acute treatment with KN93 (i.t.) also dose-dependently reversed CFA-induced thermal hyperalgesia and mechanical allodynia. The action of KN93 started in 30 min and lasted for at least 2 to 4 h. KN92 (45 nmol i.t.) [2-[N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine], an inactive analog of KN93, showed no effect on CFA-induced CaMKII activation, allodynia, or hyperalgesia. Furthermore, our previous studies identified trifluoperazine, a clinically used antipsychotic drug, to be a potent CaMKII inhibitor. Inhibition of CaMKII activity by trifluo...Continue Reading

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Citations

Oct 31, 2009·Molecular Neurobiology·Max Larsson
May 30, 2009·The Journal of Pharmacology and Experimental Therapeutics·Yan ChenZaijie Jim Wang
Mar 26, 2011·The Journal of Pharmacology and Experimental Therapeutics·Cheng YangZaijie Jim Wang
Jun 1, 2012·American Journal of Physiology. Renal Physiology·Wenbin YangDavid J Klumpp
Jan 18, 2011·Hematology·Zaijie J WangRobert Molokie
May 30, 2008·Molecular Pain·Ruth Drdla, Jürgen Sandkühler
Nov 25, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Subimal DattaElissa H Patterson
Jan 8, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yan ChenZaijie Jim Wang
Nov 12, 2013·European Journal of Pharmacology·Robert E MolokieZaijie J Wang
Oct 15, 2014·BioMed Research International·Francis Sahngun NahmPyung Bok Lee
May 23, 2012·The Journal of Pain : Official Journal of the American Pain Society·Ying HeZaijie Jim Wang
Feb 1, 2011·Free Radical Biology & Medicine·Daniela SalveminiWilliam L Neumann
Sep 12, 2009·European Journal of Pharmacology·Eniko VamosLaszlo Vecsei
Sep 1, 2009·Drug Discovery Today. Therapeutic Strategies·Elias UtrerasAshok B Kulkarni
Nov 26, 2015·Frontiers in Pharmacology·Cedric J LaedermannIsabelle Decosterd
Sep 18, 2009·Annals of the New York Academy of Sciences·Johanna WestraCees G M Kallenberg
Sep 6, 2015·Purinergic Signalling·Phuong Dao-UngLeanne Stokes
May 16, 2015·Pediatric Blood & Cancer·Amanda M BrandowJulie A Panepinto
Jul 28, 2016·The Journal of Pharmacology and Experimental Therapeutics·Zhen LiFang Luo
Apr 3, 2010·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Max Larsson, Jonas Broman
Jul 26, 2017·Cephalalgia : an International Journal of Headache·Roshni RamachandranInger Jansen-Olesen
Mar 29, 2018·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Kanika GuptaKalpna Gupta
Sep 1, 2017·The Journal of Pharmacology and Experimental Therapeutics·Ya-Qun ZhouDa-Wei Ye
Dec 18, 2014·The Journal of Pharmacology and Experimental Therapeutics·Xiaoyu HuZaijie Jim Wang
Sep 3, 2016·Metabolic Brain Disease·Shuo LiMing-Gao Zhao

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