Activation of spinal chemokine receptor CXCR3 mediates bone cancer pain through an Akt-ERK crosstalk pathway in rats

被引：84

作者：

Guan, Xue-Hai ^{[1
]}

Fu, Qiao-Chu ^{[1
]}

Shi, Dai ^{[1
]}

Bu, Hui-Lian ^{[1
]}

Song, Zhen-Peng ^{[1
]}

Xiong, Bing-Rui ^{[1
]}

Shu, Bin ^{[1
]}

Xiang, Hong-Bing ^{[1
]}

Xu, Bing ^{[2
]}

Manyande, Anne ^{[3
]}

Cao, Fei ^{[1
,4
]}

Tian, Yu-Ke ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Anesthesiol & Pain Med, 1095 Jiefang Rd, Wuhan 430030, Peoples R China

[2] Guangxi Univ Chinese Med, Affiliated Hosp 3, Dept Neurol, Liuzhou Tradit Chinese Med Hosp, Liuzhou 545001, Peoples R China

[3] Univ West London, Sch Psychol Social Work & Human Sci, London, England

[4] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA

来源：

EXPERIMENTAL NEUROLOGY | 2015年 / 263卷

基金：

中国国家自然科学基金;

关键词：

Bone cancer; Pain; CXCR3; ERK; Akt; PROTEIN-KINASE B/AKT; AIRWAY EPITHELIAL-CELLS; DORSAL-ROOT GANGLION; SIGNALING PATHWAY; PHOSPHATIDYLINOSITOL; 3-KINASE; MECHANICAL ALLODYNIA; NEUROPATHIC PAIN; NERVE LIGATION; MAP KINASE; CENTRAL SENSITIZATION;

D O I：

10.1016/j.expneurol.2014.09.019

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Previously, we showed that activation of the spinal CXCL9, 10/CXCR3 pathway mediated bone cancer pain (BCP) in rats. However, the cellular mechanism involved is poorly understood. Here, we found that the activated CXCR3 was co-localized with either neurons, microglia, and astrocytes in the spinal cord, or non-peptidergic-, peptidergic-, and A-type neurons in the dorsal root ganglion. The inoculation of Walker-256 mammary gland carcinoma cells into the rat's tibia induced a time-dependent phosphorylation of Akt and extracellular signal-regulated kinase (ERK1/2) in the spinal cord, and CXCR3 was necessary for the phosphorylation of Akt and ERK 1/2. Meanwhile, CXCR3 was co-localized with either pAkt or pERK1/2. Blockage of either Akt or ERK1/2 prevented or reversed the mechanical allodynia in BCP rats. Furthermore, there was cross-activation between PI3K/Akt and Raf/MEK/ERK pathway under the BCP condition. Our results demonstrated that the activation of spinal chemokine receptor CXCR3 mediated BCP through Akt and ERK 1/2 kinase, and also indicated a crosstalk between PI3K/Alct and Raf/MEK/ERK signaling pathways under the BCP condition. Crown Copyright (C) 2014 Published by Elsevier Inc. All rights reserved.

引用

页码：39 / 49

页数：11

共 103 条

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