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Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain.

Nature neuroscience | 2016

Although microglia have been implicated in nerve injury-induced neuropathic pain, the manner by which injured sensory neurons engage microglia remains unclear. We found that peripheral nerve injury induced de novo expression of colony-stimulating factor 1 (CSF1) in injured sensory neurons. CSF1 was transported to the spinal cord, where it targeted the microglial CSF1 receptor (CSF1R). Cre-mediated sensory neuron deletion of Csf1 completely prevented nerve injury-induced mechanical hypersensitivity and reduced microglial activation and proliferation. In contrast, intrathecal injection of CSF1 induced mechanical hypersensitivity and microglial proliferation. Nerve injury also upregulated CSF1 in motoneurons, where it was required for ventral horn microglial activation and proliferation. Downstream of CSF1R, we found that the microglial membrane adaptor protein DAP12 was required for both nerve injury- and intrathecal CSF1-induced upregulation of pain-related microglial genes and the ensuing pain, but not for microglial proliferation. Thus, both CSF1 and DAP12 are potential targets for the pharmacotherapy of neuropathic pain.

Pubmed ID: 26642091 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

Associated grants

  • Agency: NIA NIH HHS, United States
    Id: AG045040
  • Agency: NIDCR NIH HHS, United States
    Id: DE022001
  • Agency: NINDS NIH HHS, United States
    Id: K08 NS078050
  • Agency: NIAID NIH HHS, United States
    Id: AI068129
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS014627
  • Agency: NINDS NIH HHS, United States
    Id: NS14627
  • Agency: NINDS NIH HHS, United States
    Id: K08NS078050
  • Agency: NINDS NIH HHS, United States
    Id: R37 NS014627
  • Agency: NIA NIH HHS, United States
    Id: R01 AG045040
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI068129
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA036985
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE022001
  • Agency: Wellcome Trust, United Kingdom

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