期刊
NATURE NEUROSCIENCE
卷 19, 期 1, 页码 94-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4189
关键词
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资金
- Foundation for Anesthesia Education and Research (FAER) [MRTG-BS-02/15/2010-G]
- US National Institutes of Health [K08NS078050]
- DFG [KU 3039/1-1]
- Wellcome Trust
- [NIH-DE022001]
- [NIH-NS14627]
- [NIH-AG045040]
- [NIH-AI068129]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI068129] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE022001] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R37NS014627, R01NS014627, K08NS078050] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG045040] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA036985] Funding Source: NIH RePORTER
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.
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