Muscone relieves inflammatory pain by inhibiting microglial activation-mediated inflammatory response via abrogation of the NOX4/JAK2-STAT3 pathway and NLRP3 inflammasome

Abstract

Previous studies have shown that muscone, a pharmacologically active ingredient isolated from musk, has excellent effects on anti-inflammation. However, its effect on microglia activation-induced inflammatory pain is not known yet. In the present study, a mouse BV2 microglia cell activation-mediated inflammatory model was developed with LPS induction, and a mouse inflammatory pain model was established with CFA injection. The inhibitory effect of muscone on microglia inflammatory activation was verified by measuring pro-inflammatory cytokines expression (interleukin-6, tumor necrosis factor-α, and interleukin-1β; IL-6, TNF-α and IL-1β). We found that muscone suppressed microglial activation-mediated inflammatory response through the NADPH oxidase 4 (NOX4)/janus kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway and pyrin-domain-containing 3 (NLRP3) inflammasome. Notably, muscone mitigated CFA-induced pain hypersensitivity and inflammation, as well as microglia cell activation in vivo. Furthermore, muscone inhibited the CFA-induced NOX4, p-JAK2/p-STAT3, and NLRP3 inflammasome expression in spinal cord of mice. In conclusion, this study uncovered that muscone relieved inflammatory pain by inhibiting microglial activation-mediated inflammatory response via abrogation of the NOX4/JAK2-STAT3 pathway and NLRP3 inflammasome. This finding of muscone is promising for treating inflammatory pain.