STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex
Cancers(2022)
摘要
The medial prefrontal cortex (mPFC) is the main cortical area for processing both sensory and affective aspects of pain. Recently, mPFC was reported to participate in cancer-induced bone pain (CIBP) via the mechanism of central inflammation. STING is a key component of neuroinflammation in the central neuron system by activating downstream TBK1 and NF-κB signaling pathways. We aimed to investigate whether STING regulated neuroinflammation in the mPFC in rat models of CIBP. It is worth noting that we found a significant upregulation of STING in the mPFC after CIBP, accompanied by activation of TBK1 and NF-κB signaling pathways. In addition, pain and anxiety-like behaviors were alleviated by intraperitoneal injection of the STING inhibitor C-176. Furthermore, in microglia GMI-R1 cells, C-176 reversed LPS-induced M1 polarization. Collectively, this evidence indicated that STING may contribute to cancer-induced bone pain by activating TBK1 and NF-κB, and by promoting M1 polarization of microglia in the mPFC.
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关键词
medial prefrontal cortex,STING,M1 microglia,cancer-induced bone pain
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