MHCII contributes to bone cancer pain via activating the NLRP3 inflammasome in microglia of the medial prefrontal cortex

Abstract As one of the causes of bone cancer pain (BCP), central hyperalgesia has more and more supporting evidence recently. The medial prefrontal cortex (mPFC) is implicated in emotional disorders associated with BCP. Major histocompatibility complex II (MHCII) is a key component in regulating anti-inflammatory response and antigen presentation. This study aims to investigate whether MHCII of the mPFC participates in the BCP. The rat model of BCP was established by injecting Walker 256 cells into the tibia. BCP-induced decreased pain threshold, increased the expression of MHCII and the downstream protein CTSS, CD74 and upstream protein CIITA in mPFC, and the upregulation of MHCII was mainly observed in the mPFC microglia. Furthermore, pharmacological inhibition of MHCII in mPFC by intraperitoneal injecting minocycline provides relief from BCP. Importantly, the upregulation of MHCII is accompanied by significant NLRP3 inflammasome activation and inflammatory factors (IL-1β, IL-18 and TNF-α) released in the mPFC of BCP rats. Taken together, our data suggest that MHCII participates in BCP by activating NLRP3 inflammasome in microglia of the mPFC.