Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2: Further Insights into Molecular, Synaptic, and Cellular Mechanisms.
Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2: Further Insights into Molecular, Synaptic, and Cellular Mechanisms.
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脊髓 CCL2 通过 CCR2 促进中枢敏化、长时程增强和炎症疼痛：进一步深入了解分子、突触和细胞机制
DOI：
10.1007/s12264-017-0106-5
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发表时间：
2018-03
影响因子：
5.6
通讯作者：
Ji RR
中科院分区：
文献类型：
--
作者：
Xie RG;Gao YJ;Park CK;Lu N;Luo C;Wang WT;Wu SX;Ji RR
越来越多的证据支持由脊髓星形胶质细胞产生的趋化因子在促进中枢致敏和慢性疼痛中的重要作用。特别是，CCL2被证明可以增强nmda诱导的脊髓外层II （IIo）神经元电流。然而，CCL2调节中枢致敏的确切分子、突触和细胞机制尚不清楚。脊髓注射CCR2拮抗剂RS504393可减轻CCR2和炎症性痛觉过敏。单细胞RT-PCR显示CCR2在vGluT2+兴奋性神经元中表达。CCL2增加了IIo层CCR2+/vGluT2+神经元的nmda诱导电流。CCL2也增强了背根刺激后诱发的突触NMDA电流。此外，CCL2增加了表达生长抑素的兴奋性神经元的总NMDA电流和突触NMDA电流。最后，鞘内RS504393逆转了脊髓c纤维刺激诱发的长期增强。我们的研究结果表明，CCL2在脊髓ii层表达ccr2的兴奋性神经元中直接调节突触可塑性，这是病理性疼痛中枢致敏产生的基础。
Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 was shown to enhance NMDA-induced currents in spinal outer lamina II (IIo) neurons. However, the exact molecular, synaptic, and cellular mechanisms of the CCL2 modulation of central sensitization are still unclear. Spinal injection of the CCR2 antagonist RS504393 attenuated CCL2 and inflammation-induced hyperalgesia. Single-cell RT-PCR revealed CCR2 expression in vGluT2+ excitatory neurons. CCL2 increased NMDA-induced currents in CCR2+/vGluT2+ neurons in lamina IIo. CCL2 also enhanced evoked synaptic NMDA currents following dorsal root stimulation. Furthermore, CCL2 increased total and synaptic NMDA currents in somatostatin-expressing excitatory neurons. Finally, intrathecal RS504393 reversed C-fiber stimulation-evoked long-term potentiation in the spinal cord. Our findings suggest a direct modulation of synaptic plasticity by CCL2 in CCR2-expressing excitatory neurons in the spinal cord lamina IIo underlying the generation of central sensitization in pathological pain.
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影响因子：
25
作者：
Ji, RR;Baba, H;Woolf, CJ
通讯作者：
Woolf, CJ
影响因子：
64.5
作者：
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q
通讯作者：
Ma Q
影响因子：
5.6
作者：
Guo, Wei;Wang, Hu;Zou, Shiping;Dubner, Ronald;Ren, Ke
通讯作者：
Ren, Ke
小胶质细胞 P2X7 受体和下游信号通路参与脊髓伤害性反应的长期增强
影响因子：
15.1
作者：
Chu, Yu-Xia;Zhang, Yan;Zhao, Zhi-Qi
通讯作者：
Zhao, Zhi-Qi
DOI：
10.1126/science.aah5715
发表时间：
2016-12-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kronschläger MT;Drdla-Schutting R;Gassner M;Honsek SD;Teuchmann HL;Sandkühler J
通讯作者：
Sandkühler J