Chemokine CXCL1 enhances inflammatory pain and increases NMDA receptor activity and COX-2 expression in spinal cord neurons via activation of CXCR2.
Chemokine CXCL1 enhances inflammatory pain and increases NMDA receptor activity and COX-2 expression in spinal cord neurons via activation of CXCR2.
复制标题
趋化因子 CXCL1 通过激活 CXCR2 增强脊髓神经元中的炎性疼痛并增加 NMDA 受体活性和 COX-2 表达
DOI：
10.1016/j.expneurol.2014.05.014
复制
发表时间：
2014-11
影响因子：
5.3
通讯作者：
Gao, Yong-Jing
中科院分区：
文献类型：
--
作者：
Cao, De-Li;Zhang, Zhi-Jun;Xie, Rou-Gang;Jiang, Bao-Chun;Ji, Ru-Rong;Gao, Yong-Jing
关键词：
最近的研究表明，CXCL1在脊髓星形胶质细胞中的上调参与了神经性疼痛的维持。然而，CXCL1是否以及如何调节炎症性疼痛仍然未知。本研究表明，足底注射CFA可在注射后6小时和3天增加脊髓中CXCL1及其主要受体CXCR2的mRNA和蛋白表达。免疫荧光双染色显示CXCL1和CXCR2分别在脊髓星形胶质细胞和神经元中表达。在cfa后第3天，鞘内注射cxcr1中和抗体或CXCR2拮抗剂SB225002可减轻cfa诱导的机械和热过敏。膜片钳记录显示，cxcr1通过CXCR2增强nmda诱导的II层神经元电流，并且这种增强在cfa处理的小鼠中进一步增强。此外，鞘内注射CXCL1增加了背角神经元中COX-2的表达，SB225002或MEK （ERK激酶）抑制剂PD98059预处理可阻断COX-2的表达。最后，用SB225002或PD98059预处理可以降低cfa诱导的热痛觉过敏、脊髓中COX-2 mRNA/蛋白的表达和ERK的激活。综上所述，我们的数据表明，CXCL1在炎症后由脊髓星形胶质细胞上调并释放，作用于表达cxcr2的脊髓神经元，增加ERK激活、突触传递和背角神经元COX-2的表达，并参与炎症性疼痛的发病机制。
Recent studies have shown that CXCL1 upregulation in spinal astrocytes is involved in the maintenance of neuropathic pain. However, whether and how CXCL1 regulates inflammatory pain remains unknown. Here we show that intraplantar injection of CFA increased mRNA and protein expressions of CXCL1 and its major receptor CXCR2 in the spinal cord at 6 hours and 3 days after the injection. Immunofluorescence double staining showed that CXCL1 and CXCR2 were expressed in spinal astrocytes and neurons, respectively. Intrathecal injection of CXCL1 neutralizing antibody or CXCR2 antagonist SB225002 attenuated CFA-induced mechanical and heat hypersensitivity on post-CFA day 3. Patch-clamp recordings showed that CXCL1 potentiated NMDA-induced currents in lamina II neurons via CXCR2, and this potentiation was further increased in CFA-treated mice. Furthermore, intrathecal injection of CXCL1 increased COX-2 expression in dorsal horn neurons, which was blocked by pretreatment with SB225002 or MEK (ERK kinase) inhibitor PD98059. Finally, pretreatment with SB225002 or PD98059 decreased CFA-induced heat hyperalgesia and COX-2 mRNA/protein expression and ERK activation in the spinal cord. Taken together, our data suggest that CXCL1, upregulated and released by spinal astrocytes after inflammation, acts on CXCR2-expressing spinal neurons to increase ERK activation, synaptic transmission and COX-2 expression in dorsal horn neurons and contributes to the pathogenesis of inflammatory pain.
登录
查看更多内容
影响因子：
25
作者：
Ji, RR;Baba, H;Woolf, CJ
通讯作者：
Woolf, CJ
影响因子：
5.6
作者：
Guo, Wei;Wang, Hu;Zou, Shiping;Dubner, Ronald;Ren, Ke
通讯作者：
Ren, Ke
影响因子：
7.4
作者：
Gao YJ;Xu ZZ;Liu YC;Wen YR;Decosterd I;Ji RR
通讯作者：
Ji RR
影响因子：
8.8
作者：
Li, Huiqing;Xie, Wenrui;Zhang, Jun-Ming
通讯作者：
Zhang, Jun-Ming
影响因子：
3.5
作者：
Baba, H;Ji, RR;Woolf, CJ
通讯作者：
Woolf, CJ