Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury

Nan Gu, Jiyun Peng, Madhuvika Murugan, Xi Wang, Ukpong B. Eyo, Dongming Sun, Yi Ren, Emanuel DiCicco-Bloom, Wise Young, Hailong Dong, LongJun Wu

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here, we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT) by using two genetic mouse models (CCR2RFP/+:CX3CR1GFP/+ and CX3CR1creER/+:R26tdTomato/+ mice) as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT-induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1−/− and P2Y12−/− mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management.

Original languageEnglish (US)
Pages (from-to)605-614
Number of pages10
JournalCell Reports
Volume16
Issue number3
DOIs
StatePublished - Jul 19 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Gu, N., Peng, J., Murugan, M., Wang, X., Eyo, U. B., Sun, D., Ren, Y., DiCicco-Bloom, E., Young, W., Dong, H., & Wu, L. (2016). Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury. Cell Reports, 16(3), 605-614. https://doi.org/10.1016/j.celrep.2016.06.018