The Roles of Chemokine CXCL13 in the Development of Bone Cancer Pain and the Regulation of Morphine Analgesia in Rats

被引：18

作者：

Bu, Hui-Lian ^{[1
]}

Xia, Yu-Zhong ^{[2
]}

Liu, Pan-Mei ^{[1
]}

Guo, Hai-Ming ^{[2
]}

Yuan, Chang ^{[2
]}

Fan, Xiao-Chong ^{[1
]}

Huang, Chen ^{[1
]}

Wen, Yuan-Yuan ^{[1
]}

Kong, Cun-Long ^{[1
]}

Wang, Tao ^{[1
]}

Ma, Le-Tian ^{[1
]}

Li, Xin-Xin ^{[1
]}

Zhang, Hong-Wei ^{[3
]}

Zhang, Li-Rong ^{[3
]}

Ma, Min-Yu ^{[1
]}

Ai, Yan-Qiu ^{[2
]}

Zhang, Wei ^{[2
]}

机构：

[1] Zhengzhou Univ, Dept Pain Management, Affiliated Hosp 1, 1 Jian She Dong Rd, Zhengzhou 450052, Henan, Peoples R China

[2] Zhengzhou Univ, Dept Anesthesiol, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China

[3] Zhengzhou Univ, Sch Basic Med Sci, Zhengzhou 450000, Henan, Peoples R China

来源：

NEUROSCIENCE | 2019年 / 406卷

基金：

中国国家自然科学基金;

关键词：

CXCL13; cancer pain; morphine; signaling pathways; siRNA; MU-OPIOID RECEPTOR; P38; MAPK; CROSS-DESENSITIZATION; CELL-MIGRATION; ACTIVATION; INVOLVEMENT; HYPERALGESIA; CONTRIBUTES; MICROGLIA; PATHWAY;

D O I：

10.1016/j.neuroscience.2019.02.025

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Chemokines are important regulators of immune, inflammatory, and neuronal responses in peripheral and central pain pathway. The aim of this study was to investigate whether chemokine (C-X-C motif) ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) involve in the development of bone cancer pain (BCP) and the regulation of morphine analgesia in rats. The change of pain behaviors in BCP rats were measured by testing paw withdrawal threshold (PWT). The levels of CXCL13, CXCR5 and signal pathway proteins (p-p38, p-ERK and p-AKT etc.) in the spinal cord were measured via western blots. The expression of CXCL13 and CXCR5 in spinal cord was increased in BCP rats. The BCP rats showed decrease of PWTs, which was relieved by CXCR5i. Intrathecally injection of murine recombinant CXCL13 (mrCXCL13) decreased the PWTs of BCP rats and opposed morphine-induced analgesia in BCP rats. In BCP rats, the signal pathway proteins (p38, ERK and AKT) in the spinal cord were activated. CXCL13 and morphine had contrary effect on the phosphorylation of these proteins. MrCXCL13 directly increased the levels of p-p38, p-ERK and p-AKT in BCP rats. However, morphine decreased the levels of these proteins in BCP rats. While blocking the activation of p-p38, p-ERK and p-AKT, morphine analgesia was enhanced. These results suggest CXCL13 participated in bone cancer pain and opposed morphine analgesia via p38, ERK and AKT pathways. It may be a target to enhance pain management in cancer pain patients. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：62 / 72

页数：11

共 41 条

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Spinal IFN-γ-induced protein-10 (CXCL10) mediates metastatic breast cancer-induced bone pain by activation of microglia in rat models [J].