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CCL2 通过与脊髓伤害感受器末梢突触前 CCR2 相互作用促进脊髓突触传递和疼痛。

CCL2 facilitates spinal synaptic transmission and pain via interaction with presynaptic CCR2 in spinal nociceptor terminals.

机构信息

Department of Neurobiology, Fourth Military Medical University, Xi'an, 710032, China.

Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.

出版信息

Mol Brain. 2020 Nov 23;13(1):161. doi: 10.1186/s13041-020-00701-6.

DOI:10.1186/s13041-020-00701-6
PMID:33228784
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7685578/
Abstract

Previous studies have shown that CCL2 may cause chronic pain, but the exact mechanism of central sensitization is unclear. In this article, we further explore the presynaptic role of CCL2. Behavioral experiments show that intervertebral foramen injection CCR2 antagonists into dorsal root ganglion (DRG) can inhibit the inflammatory pain caused by CCL2 in spinal cord. We raised the question of the role of presynaptic CCR2 in the spinal dorsal horn. Subsequent electron microscopy experiments showed that CCR2 was expressed in the presynaptic CGRP terminal in the spinal dorsal horn. CCL2 can enhance presynaptic calcium signal. Whole-cell patch-clamp recordings showed that CCL2 can enhance NMDAR-eEPSCs through presynaptic effects, and further application of glutamate sensor method proved that CCL2 can act on presynaptic CCR2 to increase the release of presynaptic glutamate. In conclusion, we suggest that CCL2 can directly act on the CCR2 on presynaptic terminals of sensory neurons in the spinal dorsal horn, leading to an increase in the release of presynaptic glutamate and participate in the formation of central sensitization.

摘要

先前的研究表明 CCL2 可能引起慢性疼痛，但中枢敏化的确切机制尚不清楚。在本文中，我们进一步探讨了 CCL2 的突触前作用。行为学实验表明，向背根神经节（DRG）注射 CCR2 拮抗剂可以抑制 CCL2 在脊髓中引起的炎症性疼痛。我们提出了 CCR2 在脊髓背角中突触前作用的问题。随后的电镜实验表明，CCR2 在前角 CGRP 末梢表达。CCL2 可以增强突触前钙信号。全细胞膜片钳记录表明，CCL2 可以通过突触前作用增强 NMDAR-eEPSCs，进一步应用谷氨酸传感器方法证明 CCL2 可以作用于突触前 CCR2 以增加突触前谷氨酸的释放。总之，我们认为 CCL2 可以直接作用于脊髓背角感觉神经元的突触前末梢上的 CCR2，导致突触前谷氨酸释放增加，并参与中枢敏化的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/d0bd4bc65db7/13041_2020_701_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/2dcb29ce7755/13041_2020_701_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/30d4017b8066/13041_2020_701_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/c37addc18220/13041_2020_701_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/96d5a4469ec7/13041_2020_701_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/35ca5260ffa6/13041_2020_701_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/d0bd4bc65db7/13041_2020_701_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/2dcb29ce7755/13041_2020_701_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/30d4017b8066/13041_2020_701_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/c37addc18220/13041_2020_701_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/96d5a4469ec7/13041_2020_701_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/35ca5260ffa6/13041_2020_701_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061e/7685578/d0bd4bc65db7/13041_2020_701_Fig6_HTML.jpg

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