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.

中文翻译：

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

先前的研究表明，CCL2可能会引起慢性疼痛，但中枢致敏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。行为实验表明，椎间孔注射CCR2拮抗剂到背根神经节（DRG）可以抑制CCL2引起的脊髓炎性疼痛。我们提出了突触前 CCR2 在脊髓背角中的作用的问题。随后的电子显微镜实验表明，CCR2 在脊髓背角的突触前 CGRP 末端表达。CCL2可以增强突触前钙信号。全细胞膜片钳记录表明 CCL2 可以通过突触前效应增强 NMDAR-eEPSC，谷氨酸传感器法的进一步应用证明，CCL2可以作用于突触前CCR2，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突触前末梢的CCR2，导致突触前谷氨酸释放增加，参与中枢敏化的形成。