Fig. 6

Schematic indicating the suppression of microglial NLRP3 to alleviate morphine tolerance by procyanidins. Upon the stimulation by morphine or LPS, several pathways including the release of ROS, and K⁺ efflux have been identified to signal the activation of NLRP3 inflammasome, leading to the activation of caspase-1 and the maturation of IL-1β. Procyanidins inhibited the ROS production and NLRP3 activation. The p38/NK-κB pathway was activated by morphine or LPS to induce the gene expression of NLRP3. The inhibition of p-p38 and NF-κB were a critical mechanism for the NLRP3 inflammasome suppressive effect of procyanidins in microglia