Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Zhi-Ye ZhuangRu-Rong Ji

Abstract

Although the PI3K (phosphatidylinositol 3-kinase) pathway typically regulates cell growth and survival, increasing evidence indicates the involvement of this pathway in neural plasticity. It is unknown whether the PI3K pathway can mediate pain hypersensitivity. Intradermal injection of capsaicin and NGF produce heat hyperalgesia by activating their respective TRPV1 (transient receptor potential vanilloid receptor-1) and TrkA receptors on nociceptor sensory nerve terminals. We examined the activation of PI3K in primary sensory DRG neurons by these inflammatory agents and the contribution of PI3K activation to inflammatory pain. We further investigated the correlation between the PI3K and the ERK (extracellular signal-regulated protein kinase) pathway. Capsaicin and NGF induce phosphorylation of the PI3K downstream target AKT (protein kinase B), which is blocked by the PI3K inhibitors LY294002 and wortmannin, indicative of the activation of PI3K by both agents. ERK activation by capsaicin and NGF was also blocked by PI3K inhibitors. Similarly, intradermal capsaicin in rats activated PI3K and ERK in C-fiber DRG neurons and epidermal nerve fibers. Injection of PI3K or MEK (ERK kinase) inhibitors into the hindpaw attenuated capsaici...Continue Reading

Citations

Nov 17, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Sebastian StösserRohini Kuner
May 1, 2009·Experimental Brain Research·Martin Schmelz
May 24, 2005·Pflügers Archiv : European journal of physiology·Rosa Planells-CasesAntonio Ferrer-Montiel
Feb 18, 2010·Pflügers Archiv : European journal of physiology·John E LinleyNikita Gamper
Apr 23, 2008·Neurochemical Research·Jen-Kun Cheng, Ru-Rong Ji
Nov 6, 2010·Archives of Pharmacal Research·Eduardo Gascon, Aziz Moqrich
Jun 14, 2005·Biochemical and Biophysical Research Communications·Kwokyin HuiZhong-Ping Feng
Mar 10, 2005·Experimental Neurology·Stephen B McMahonFabien Marchand
Jun 7, 2005·Life Sciences·Luciano De Petrocellis, Vincenzo Di Marzo
Jul 9, 2013·Neuroscience Letters·Theodore J Price, Gregory Dussor
Apr 9, 2008·Nature Neuroscience·Man-Kyo ChungMichael J Caterina
Oct 10, 2012·Nature Reviews. Urology·Peter OchodnickyFrancisco Cruz
May 10, 2008·Médecine sciences : M/S·Frédéric MarmigèreJean Valmier
Feb 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Thiago M CunhaSergio H Ferreira
Sep 20, 2011·The Journal of Biological Chemistry·Shu Wang, Huai-hu Chuang
Nov 1, 2006·The Journal of General Physiology·Alexander T SteinSharona E Gordon
Nov 1, 2006·The Journal of General Physiology·Xuming Zhang, Peter A McNaughton
Apr 18, 2008·British Journal of Anaesthesia·R D'Mello, A H Dickenson
Sep 10, 2009·Brain : a Journal of Neurology·Marie-Luise SixtMichael J M Fischer
Jan 26, 2012·Brain : a Journal of Neurology·Xing-Jun LiuXu Zhang
Jan 7, 2006·Cephalalgia : an International Journal of Headache·V PuriN E J Berman
Aug 4, 2005·Science's STKE : Signal Transduction Knowledge Environment·Bernd NiliusJohn Peters
Jun 17, 2006·Annual Review of Neuroscience·Sophie Pezet, Stephen B McMahon
Jul 20, 2012·American Journal of Physiology. Endocrinology and Metabolism·Shenghao LiuQinghua Wang
Dec 24, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Xiulin ZhangWilliam C de Groat
May 2, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Simone D GueriosDale E Bjorling
Jun 3, 2011·American Journal of Physiology. Renal Physiology·Lauren Arms, Margaret A Vizzard
Nov 13, 2013·The Journal of Clinical Investigation·Zhong-Qiu ZhaoZhou-Feng Chen
Apr 29, 2005·Molecular Pain·Jeremy J Van BurenLouis S Premkumar
Jul 3, 2007·Molecular Pain·Mark H PitcherFernando Cervero
Jan 20, 2011·Environmental Health Perspectives·Jinju LiWolfgang Liedtke
Mar 29, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Erica S SchwartzG F Gebhart
Feb 11, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Qinghao XuTony L Yaksh

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