Electroacupuncture exerts an analgesic effect by inhibiting NLRP3 inflammasome activation in the periaqueductal gray in a rat model of bone cancer pain

OBJECTIVE: To investigate the effects of electroacupuncture (EA) at ST36 and BL60 in a rat model of bone cancer pain (BCP) to provide a theoretical basis and guidance for the clinical treatment of BCP. METHODS: In experiment 1, rats were assigned to sham, untreated model (BCP), EA-treated model (BCP + EA) and sham EA-treated model (BCP + SEA) groups. Pain was assessed behaviorally by a paw withdrawal threshold and limb use score. The activation of microglia and astrocytes in the periaqueductal gray was detected by immunohistochemistry. Expression of nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), caspase-1 and interleukin (IL)-1β in the periaqueductal gray matter was detected by Western blotting. A NLRP3 agonist (nigericin sodium salt (NSS)) was used in experiment 2, wherein rats were assigned to sham, BCP, BCP + EA and BCP + EA + NSS groups. For the overexpression of NLRP3, rats in the BCP + EA + NSSgroup were injected intraperitoneally with NSS on day 17 after surgery. RESULTS: EA markedly relieved BCP and suppressed the overexpression of NLRP3/caspase-1/IL-1β in the periaqueductal gray, which is related to the activation of astrocytes and microglial cells. Pharmacological activation of NLRP3 reversed the analgesic effect of EA and increased the expression of NLRP3/caspase-1/IL-1β in the periaqueductal gray. In addition, c-fos was significantly downregulated by EA and this effect was also reversed by the NLRP3 agonist, suggesting that the role of EA in BCP may involve mitigation of inflammation. CONCLUSION: EA interferes with the NLRP3/caspase-1/IL-1β pathway in the periaqueductal gray to exert an analgesic effect in this rat model of BCP.