Electroacupuncture inhibits NLRP3 inflammasome activation through CB2 receptors in inflammatory pain

The therapeutic effect of electroacupuncture (EA) on inflammatory pain has been well recognized clinically. The inflammasome promotes the maturation of the inflammatory cytokines, and EA can stimulate cannabinoid CB2 receptors in inflamed tissues. In this study we investigated whether EA inhibits NLRP3 inflammasome activation through CB2 receptors and thus relieving inflammatory pain. Assay of Caspase-1 activity and western blotting revealed that complete Freund's adjuvant (CFA) injection activated the NLRP3 inflammasome in the skin tissue in rats, which was attenuated by EA treatment. Immunofluorescence labeling showed that NLRP3 inflammasome elicited by CFA in the skin macrophages were decreased by EA. Nociceptive behavioral tests demonstrated that in CB2 receptor knockout mice, the EA effects on NLRP3 inflammasomes were largely attenuated. In addition, in vitro studies in a macrophage cell line showed that CB2 receptor stimulation inhibited the NLRP3 inflammasome activation. Thus, our results suggest a novel signaling pathway through which CB2 receptors are involved in the analgesic effect of EA on inflammatory pain. Stimulation of CB2 receptors inhibits NLRP3 inflammasome activation in inflamed skin tissues. These results suggest that EA reduces the inflammatory pain by inhibiting the activation of NLRP3 inflammasome through CB2 receptors. Our findings provide novel information about the mechanisms through which EA and CB2 receptor activation reduce inflammatory pain.