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STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex
SIMPLE SUMMARY: Cancer-induced bone pain commonly occurs in patients with bone tumors or bone metastases, and in recent years, central nervous system hyperalgesia has received increasing attention. In the present study, we confirmed STING pathways may activate M1 microglia in the mPFC after cancer-i...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656586/ https://www.ncbi.nlm.nih.gov/pubmed/36358605 http://dx.doi.org/10.3390/cancers14215188 |
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author | Zhang, Xiaoxuan Li, Xin Wang, Wei Zhang, Yuxin Gong, Zhihao Peng, Yuan Wu, Jingxiang You, Xingji |
author_facet | Zhang, Xiaoxuan Li, Xin Wang, Wei Zhang, Yuxin Gong, Zhihao Peng, Yuan Wu, Jingxiang You, Xingji |
author_sort | Zhang, Xiaoxuan |
collection | PubMed |
description | SIMPLE SUMMARY: Cancer-induced bone pain commonly occurs in patients with bone tumors or bone metastases, and in recent years, central nervous system hyperalgesia has received increasing attention. In the present study, we confirmed STING pathways may activate M1 microglia in the mPFC after cancer-induced bone pain. C-176 treatment to inhibit STING can effectively relieve cancer-induced bone pain and pain-related anxiety. In addition, in vivo or in vitro, we both found that C-176 can significantly promote the polarization of M2 microglia and inhibit M1 microglia, which provides a new direction in the treatment of cancer-induced bone pain. ABSTRACT: 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. |
format | Online Article Text |
id | pubmed-9656586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96565862022-11-15 STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex Zhang, Xiaoxuan Li, Xin Wang, Wei Zhang, Yuxin Gong, Zhihao Peng, Yuan Wu, Jingxiang You, Xingji Cancers (Basel) Article SIMPLE SUMMARY: Cancer-induced bone pain commonly occurs in patients with bone tumors or bone metastases, and in recent years, central nervous system hyperalgesia has received increasing attention. In the present study, we confirmed STING pathways may activate M1 microglia in the mPFC after cancer-induced bone pain. C-176 treatment to inhibit STING can effectively relieve cancer-induced bone pain and pain-related anxiety. In addition, in vivo or in vitro, we both found that C-176 can significantly promote the polarization of M2 microglia and inhibit M1 microglia, which provides a new direction in the treatment of cancer-induced bone pain. ABSTRACT: 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. MDPI 2022-10-22 /pmc/articles/PMC9656586/ /pubmed/36358605 http://dx.doi.org/10.3390/cancers14215188 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Xiaoxuan Li, Xin Wang, Wei Zhang, Yuxin Gong, Zhihao Peng, Yuan Wu, Jingxiang You, Xingji STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
title | STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
title_full | STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
title_fullStr | STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
title_full_unstemmed | STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
title_short | STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
title_sort | sting contributes to cancer-induced bone pain by promoting m1 polarization of microglia in the medial prefrontal cortex |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656586/ https://www.ncbi.nlm.nih.gov/pubmed/36358605 http://dx.doi.org/10.3390/cancers14215188 |
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