Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2: Further Insights into Molecular, Synaptic, and Cellular Mechanisms.

Published

Journal Article

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 NMDA-induced 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 somatostatin-expressing 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.

Full Text

Duke Authors

Cited Authors

  • Xie, R-G; Gao, Y-J; Park, C-K; Lu, N; Luo, C; Wang, W-T; Wu, S-X; Ji, R-R

Published Date

  • February 2018

Published In

Volume / Issue

  • 34 / 1

Start / End Page

  • 13 - 21

PubMed ID

  • 28265898

Pubmed Central ID

  • 28265898

Electronic International Standard Serial Number (EISSN)

  • 1995-8218

International Standard Serial Number (ISSN)

  • 1673-7067

Digital Object Identifier (DOI)

  • 10.1007/s12264-017-0106-5

Language

  • eng