Related Experiment Video
Updated: Jun 26, 2025
Increased Recovery Time and Decreased LPS Administration to Study the Vagus Nerve Stimulation Mechanisms in Limited Inflammatory Responses
Published on: March 29, 2017
C-176 reduces inflammation-induced pain by blocking the cGAS-STING pathway in microglia
Shan-Ming Yang1,2, Yuan-Bo Li3, Hua-Xing Si1,2
1College of Life Science, Northwest University, Xi'an, China.
Objective:
Inflammatory pain, is caused by lesions or diseases of the somatosensory tissue, is a prevalent chronic condition that profoundly impacts the quality of life. However, clinical treatment for this type of pain remains limited. Traditionally, the stimulation of microglia and subsequent inflammatory reactions are considered crucial elements to promote the worsening of inflammatory pain. Recent research has shown the crucial importance of the cGAS-STING pathway in promoting inflammation. It is still uncertain if the cGAS-STING pathway plays the role in the fundamental cause of inflammatory pain. We aim to explore the treatment of inflammatory pain by interfering with cGAS-STING signaling pathway.
Methods:
In this study, we established an inflammatory pain model by CFA into the plantar of mice. Activation of microglia, various inflammatory factors and cGAS-STING protein in the spinal dorsal horn were evaluated. Immunofluorescence staining was used to observe the cellular localization of cGAS and STING. The cGAS-STING pathway proteins expression and mRNA expression of indicated microglial M1/M2 phenotypic markers in the BV2 microglia were detected. STING inhibitor C-176 was intrathecal injected into mice with inflammatory pain, and the pain behavior and microglia were observed.
Results:
This research showed that injecting CFA into the left hind paw of mice caused mechanical allodynia and increased inflammation in the spine. Our research results suggested that the cGAS-STING pathway had a function in the inflammation mediated by microglia in the spinal cord dorsal horn. Blocking the cGAS-STING pathway using STING antagonists (C-176) led to reduced release of inflammatory factors and prevented M1 polarization of BV2 microglia in a laboratory setting. Additionally, intrathecal administration of C-176 reduced the allodynia in CFA treated mice.
Conclusion:
Our results suggest that inhibiting microglial polarization through the cGAS-STING pathway represents a potential novel therapeutic strategy for inflammatory pain.
Insights
This study investigated the cGAS-STING pathway
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Inflammatory pain significantly impacts quality of life, with limited treatment options.
- Microglia activation and inflammatory responses are key drivers of inflammatory pain.
- The cGAS-STING pathway's role in inflammation is recognized, but its direct involvement in inflammatory pain is unclear.
Purpose of the Study:
- To investigate the role of the cGAS-STING pathway in inflammatory pain.
- To explore the potential of targeting the cGAS-STING pathway for inflammatory pain treatment.
Main Methods:
- An inflammatory pain model was induced in mice using CFA.
- Microglial activation, inflammatory factors, and cGAS-STING pathway components were analyzed.
- The effects of a STING inhibitor (C-176) on pain behavior and microglia were assessed.
Main Results:
- CFA injection induced mechanical allodynia and spinal inflammation.
- The cGAS-STING pathway was implicated in microglia-mediated spinal cord inflammation.
- STING inhibition reduced inflammatory factors, prevented M1 microglia polarization, and alleviated allodynia.
Conclusions:
- Inhibiting microglial polarization via the cGAS-STING pathway is a potential therapeutic strategy for inflammatory pain.
- Targeting the cGAS-STING pathway offers a novel approach to managing inflammatory pain.
Related Concept Videos
01:44Nociception
01:20The JAK-STAT Signaling Pathway