PloS one · 2025
Caveolin-1 knockout improves CFA-induced inflammatory pain in adult mice through modulating the cGAS STING pathway and autophagy.
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Chang Huan, Cheng Cancan, Zheng Ning, Zhu Haiyan, Yang Hui, Zhu Xiaocheng, Zhang Fan
Аннотация
BACKGROUND: Inflammatory pain poses a significant clinical challenge, with its underlying mechanisms not yet fully elucidated. This study investigated the role of Caveolin-1 (Cav1) in inflammatory pain and elucidated its molecular mechanisms.
METHODS: We analyzed public databases and employed a mouse model of inflammatory pain induced by complete Freund's adjuvant (CFA). Cav1-knockout (Cav1-/-) mice were used to evaluate Cav1's function. The study incorporated behavioral tests, immunohistochemistry and molecular analyses. BV2 microglial cells served as the in vitro model.
RESULTS: Following CFA injection, Cav1 expression was markedly elevated in the dorsal horn of spinal cord, correlating with pain behavior and inflammatory responses. Cav1-/- mice demonstrated significantly reduced pain behavior and inflammatory responses after CFA induction. Mechanistically, Cav1 enhanced inflammation by activating the cGAS-STING pathway and inhibiting autophagy. In BV2 microglia, Cav1 overexpression increased proinflammatory cytokine expression (TNF-α, IL-1β, IL-6) while inhibiting autophagy, whereas Cav1 knockdown produced opposing effects.
CONCLUSION: This study reveals a novel role of Cav1 in inflammatory pain, demonstrating its regulation of inflammation through modulation of the cGAS-STING pathway and autophagy. These findings advance our understanding of the pathogenesis of inflammatory pain and identify Cav1 as a potential therapeutic target.
METHODS: We analyzed public databases and employed a mouse model of inflammatory pain induced by complete Freund's adjuvant (CFA). Cav1-knockout (Cav1-/-) mice were used to evaluate Cav1's function. The study incorporated behavioral tests, immunohistochemistry and molecular analyses. BV2 microglial cells served as the in vitro model.
RESULTS: Following CFA injection, Cav1 expression was markedly elevated in the dorsal horn of spinal cord, correlating with pain behavior and inflammatory responses. Cav1-/- mice demonstrated significantly reduced pain behavior and inflammatory responses after CFA induction. Mechanistically, Cav1 enhanced inflammation by activating the cGAS-STING pathway and inhibiting autophagy. In BV2 microglia, Cav1 overexpression increased proinflammatory cytokine expression (TNF-α, IL-1β, IL-6) while inhibiting autophagy, whereas Cav1 knockdown produced opposing effects.
CONCLUSION: This study reveals a novel role of Cav1 in inflammatory pain, demonstrating its regulation of inflammation through modulation of the cGAS-STING pathway and autophagy. These findings advance our understanding of the pathogenesis of inflammatory pain and identify Cav1 as a potential therapeutic target.