The effect of targeting extracellular matrix metalloproteinases on chronic inflammatory pain in mice and its mechanisms
Objective:To investigate the effect of targeting the extracellular matrix on chronic inflammatory pain in mice and its mechanisms.Methods:A chronic inflammatory pain model in mice was induced using complete Freund's adjuvant(CFA).The changes in mechanical pain threshold in the model mice were assessed using von Frey filaments.Tissues from the site of CFA injection were collected for RNAseq library construction and sequencing.The overexpression of matrix metalloproteinases(MMPs),specifically MMP-8 and MMP-12,was further validated using q-PCR.The SwissDock algorithm was employed to screen for active herbal components that inhibit MMP-8 and MMP-12,and the analgesic effects of these MMP inhibitors were tested through behavioral experiments.Results:The model of chronic inflammatory pain in mice was successfully established.Transcriptomic analysis revealed widespread activation of inflammation and immune-related pathways in the CFA group,with significant upregulation of MMP family genes(P＜0.05).Luteolin,a compound targeting MMPs,significantly alleviated chronic inflammatory pain in the model mice(P＜0.05).Further GO and GSEA analyses showed that after luteolin treatment,the expression of inflammatory and immune molecules in the model mice was significantly reduced(P＜0.05),and related pathways were inhibited as well.Conclusion:MMPs represent a novel target for chronic inflammatory pain.The active herbal component luteolin can target matrix metalloproteinases,inhibit inflammation and immune responses,and exert an analgesic effect in vivo.
万方数据
维普
