Knockdown of PAC1 improved inflammatory pain in mice by regulating the RAGE/TLR4/NF-?B signaling pathway

The development of inflammatory pain seriously affects the activities and general functions of patients in daily life. At present, the research on the mechanism of pain relief is still insufficient. This study aimed to investigate the influence of PAC1 on the progression of inflammatory pain and its molecular mechanism. Lipopolysaccharide (LPS) was used to induce BV2 microglia activation to establish an inflammation model, and CFA injection was used to establish a mouse inflammatory pain model. The results showed that PAC1 was highly expressed in BV2 microglia induced by LPS. Knockdown of PAC1 significantly reduced LPS-induced inflammation and apoptosis in BV2 cells, and RAGE/TLR4/NF-kappa B signaling pathway was involved in the regulation of BV2 cells by PAC1. What's more, knockdown of PAC1 alleviated CFA-induced mechanical allodynia and thermal hyperalgesia in mice, as well as reduced the development of inflammatory pain to a certain extent. Therefore, Knockdown of PAC1 relieved inflammatory pain in mice by inhibiting the RAGE/TLR4/NF-kappa B signaling pathway. Targeting PAC1 may be a new direction for the treatment of inflammatory pain.