Figure 2.

Functions of spinal microglia in peripheral nerve injury. When the peripheral nerve is injured, the colony-stimulating factor 1 (CSF1) is rapidly induced in DRG neurons. CSF1 transported to the spinal dorsal horn acts on the CSF1 receptor (CSF1R) of microglia, for their proliferation and activation. In the dorsal horn, the interferon regulatory factor 5 (IRF5) and IRF8, which are transcription factors, are induced in the activated microglia, followed by the release of several cytokines (including the tumor necrosis factors α, interleukin 1β, and the brain-derived neurotrophic factor), via which hypersensitivity is induced and maintained. Microglia activated by CSF1 in the ventral horn block signals from inhibitory synapses by synaptic stripping and induce the expression of several factors, which stimulates the degeneration and regeneration of injured nerves.