【摘 要】
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Mounting evidence supports an important role of chemokines,produced by spinal cord astrocytes,in promoting central sensitization and chronic pain.In particular,CCL2 (C-C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-induc
【机 构】
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Department of Neurobiology and Collaborative Innovation Center for Brain Science,The Fourth Military
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Mounting evidence supports an important role of chemokines,produced by spinal cord astrocytes,in promoting central sensitization and chronic pain.In particular,CCL2 (C-C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-induced currents in spinal outer lamina Ⅱ (Ⅱo) neurons.However,the exact molecular,synaptic,and cellular mechanisms by which CCL2 modulates central sensitization are still unclear.We found that spinal injection of the CCR2 antagonist RS504393 attenuated CCL2-and inflammation-induced hyperalgesia.Single-cell RT-PCR revealed CCR2 expression in excitatory vesicular glutamate transporter subtype 2-positive (VGLUT2+) neurons.CCL2 increased NMDAinduced currents in CCR2+/VGLUT2+ neurons in lamina Ⅱo;it also enhanced the synaptic NMDA currents evoked by dorsal root stimulation;and furthermore,it increased the total and synaptic NMDA currents in somatostatinexpressing excitatory neurons.Finally,intrathecal RS504393 reversed the long-term potentiation evoked in the spinal cord by C-fiber stimulation.Our findings suggest that CCL2 directly modulates synaptic plasticity in CCR2-expressing excitatory neurons in spinal lamina Ⅱo,and this underlies the generation of central sensitization in pathological pain.
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