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Review
. 2021 Mar 9;6(1):e883.
doi: 10.1097/PR9.0000000000000883. eCollection 2021.

Contribution of colony-stimulating factor 1 to neuropathic pain

Xiaobing Yu  1 , Allan Basbaum  2 , Zhonghui Guan  1
Affiliations
Review

Contribution of colony-stimulating factor 1 to neuropathic pain

Xiaobing Yu et al. Pain Rep. .

Abstract

Molecular and cellular interactions among spinal dorsal horn neurons and microglia, the resident macrophages of the central nervous system, contribute to the induction and maintenance of neuropathic pain after peripheral nerve injury. Emerging evidence also demonstrates that reciprocal interactions between macrophages and nociceptive sensory neurons in the dorsal root ganglion contribute to the initiation and persistence of nerve injury-induced mechanical hypersensitivity (allodynia). We previously reported that sensory neuron-derived colony-stimulating factor 1 (CSF1), by engaging the CSF1 receptor (CSF1R) that is expressed by both microglia and macrophages, triggers the nerve injury-induced expansion of both resident microglia in the spinal cord and macrophages in the dorsal root ganglion and induces their respective contributions to the neuropathic pain phenotype. Here, we review recent research and discuss unanswered questions regarding CSF1/CSF1R-mediated microglial and macrophage signaling in the generation of neuropathic pain.

Keywords: Neuropathic pain; dorsal root ganglion; macrophage; microglia; spinal cord.

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Conflict of interest statement

The authors have no conflicts of interest to declare. A patent “Targeted Disruption of a CSF1-DAP12 Pathway Member Gene for the Treatment of Neuropathic Pain” has been filed by the authors.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1.
Figure 1.
Sensory neuron-derived CSF1 triggers nerve injury-induced expansion of both resident microglia in the spinal cord and macrophages in the DRG. Peripheral nerve injury induces de novo expression of CSF1 in injured sensory neurons. The CSF1, in turn, is released from DRG neurons and stimulates proliferation of surrounding macrophages. The CSF1 is also transported to the spinal cord dorsal horn, where it engages the CSF1 receptor and stimulates microglia. The activated microglia undergo a DAP12-independent pathway that induces microglia proliferation and a DAP12-dependent pathway that induces expression of a host of neuropathic pain–associated genes. The figure is adapted from our previous article. DRG, dorsal root ganglion; CSF1, colony-stimulating factor 1.
See this image and copyright information in PMC

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