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

Publication date: Available online 30 June 2016
Source:Cell Reports
Author(s): Nan Gu, Jiyun Peng, Madhuvika Murugan, Xi Wang, Ukpong B. Eyo, Dongming Sun, Yi Ren, Emanuel DiCicco-Bloom, Wise Young, Hailong Dong, Long-Jun Wu
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 (CCR2^RFP/+:CX3CR1^GFP/+ and CX3CR1^creER/+:R26^tdTomato/+ 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.

Graphical abstract

Teaser

Gu et al. show that resident microglial proliferation is the major contributor to microgliosis in the spinal dorsal horn after peripheral nerve injury. However, there is no monocyte infiltration associated with injury-induced microgliosis in the dorsal horn. Pharmacological or genetic inhibition of microglial proliferation attenuates neuropathic pain hypersensitivity.


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