Caveolin-1 knockout improves CFA-induced inflammatory pain in adult mice through modulating the cGAS STING pathway and autophagy.

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.