To explore the pain-relieving effect of Zisheng Shenqi Pills on the mouse model of writhing induced by acetic acid.Methods:Forty-two mice were randomized into 7 groups and administrated with corresponding drug solutions by gavage.The model was established 1 h after the last administration.The writhing times of mice were observed，and the writhing inhibition rate was calculated.The enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1β(IL-1β)，prostaglandin E2(PGE2)，and nerve growth factor(NGF) in the serum.The mRNA levels of purinergic receptor P2X，ligand-gated ion channel 7(P2X7R)，Nod-like receptor protein 3(NLRP3)，and NIMA-related kinase 7(NEK7) were determined by RT-PCR.Results:Compared with the model group，Zisheng Shenqi Pills at low，medium，and high doses inhibited the writhing response，reduced the writhing times，increased the inhibition rate of writhing，and lowered the levels of IL-1β，PGE2，and NGF in the serum of mice.Moreover，they down-regulated the mRNA levels of P2X7R，NLRP3，and NEK7 to inhibit the pain response.The high dose group demonstrated the best effect(P<0.05)，which was similar to that of indometacin and Tongfengshu Tablets.Conclusion:Zisheng Shenqi Pills at high doses can significantly lower the levels of pain factors in the serum of mice by regulating the P2X7R signaling pathway.