Phosphatidylinositol 3-kinase mediates pain behaviors induced by activation of peripheral ephrinBs/EphBs signaling in mice

被引:37
|
作者
Guan, Xue-Hai [2 ]
Lu, Xian-Fu [2 ]
Zhang, Hong-Xing [2 ]
Wu, Jing-Ru [2 ]
Yuan, Yan [2 ]
Bao, Qi [2 ]
Ling, Di-Yang [2 ]
Cao, Jun-Li [1 ,2 ]
机构
[1] Xuzhou Med Coll, Affiliated Hosp, Dept Anesthesiol, Xuzhou 221002, Jiangsu, Peoples R China
[2] Jiangsu Inst Anesthesiol, Jiangsu Key Lab Anesthesiol, Xuzhou 221002, Jiangsu, Peoples R China
关键词
EphB; EphrinB; Phosphatidylinositol; 3-kinase; Extracellular signal-regulated kinase; Peripheral sensitization; Hyperalgesia; Fos; PROTEIN-KINASE B/AKT; DORSAL-ROOT GANGLION; EPIDERMAL-KERATINOCYTES; NEUROPATHIC PAIN; EPH RECEPTORS; PHOSPHOINOSITIDE; 3-KINASE; THERMAL HYPERALGESIA; SENSORY NEURONS; PATHWAY; CONTRIBUTES;
D O I
10.1016/j.pbb.2010.02.007
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
EphBs receptors and their ephrinBs ligands are present in the adult brain and peripheral tissue and play a critical role in modulating multiple aspects of physiology and pathophysiology. Our recent evidence has shown that ephrinBs acted as a sensitizer to participate in peripheral sensitization and hyperalgesia induced by activation of peripheral ephrinBs/EphBs signaling. In the present study, we explored the role of phosphatidylinositol 3-kinase (PI3K) in ephrinB1-Fc-induced pain behaviors. Intraplantar injection of ephrinB1-Fc produced a time- and dose-dependent increase of PI3K-p110 gamma expression and of phosphorylation of AKT in skin of injection site. Pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented activation of peripheral AKT by ephrinB1-Fc. The activated AKT expressed in peripheral nerve terminals and DRG peptide-containing and small non-peptide-containing neurons. Inhibition of peripheral PI3K signaling dose-dependently prevented and reversed pain behaviors and spinal Fos protein expression induced by intraplantar injection of ephrinB1-Fc. Furthermore, pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented ephrinB1-Fc-induced ERK activation in a dose-dependent manner. These data demonstrated that PI3K and PI3K crosstalk to ERK signaling mediated pain behaviors induced by activation of peripheral ephrinBs/EphBs signaling in mice. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:315 / 324
页数:10
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