Mast cell deficient and AZ10606120 alleviated high concentrations of ATP-induced inflammation pain. (A) Compared with C57/BL mice, Sash mice alleviated the paw swelling. (B) Compared with the C57/BL mice, the infiltration of inflammatory cells in Sash mice was significantly reduced. (a-b, HE staining of saline and ATP groups in C57/BL mice; c-d, HE staining of saline and ATP groups in Sash mice, 250X). (C) Compared with C57BL mice, Sash mice significantly reduced paw thickening (*p < 0.05, **p < 0.01, WT group vs Sash group, n=8 and 6 respectively). (D) High concentrations of ATP induced mast cells degranulation (The construction of Mrgprb2-Cre tdT +mice was to integrate the fluorescent protein of Td/Tomato into the promoter of MrgprB2, red represented mast cells, and the small red granules around mast cells represented degranulation). (E) Sash mice alleviated the mechanical hyperalgesia induced by high concentrations of ATP (*p < 0.05, WT group vs Sash group, n=8 and 6 respectively). (F) Mast cell deficient attenuated the upregulation of IL-1β and CCL3 (**p < 0.01, ***p < 0.001, saline group vs ATP group, #p < 0.05, ##p < 0.01, WT (ATP) group vs Sash (ATP) group). (G) The infiltration of mast cells expressing P2X7R was significantly increased, which could be inhibited by Z10606120. (H) AZ10606120 significantly relieved the mechanical hyperalgesia. (*p < 0.05, **p < 0.01, ATP group vs ATP+AZ10606120 group). (I) AZ10606120 attenuated the up-regulation of IL-6 and CCL3 (*p < 0.05, ***p < 0.001, saline group vs ATP group, #p < 0.05, ###p < 0.001, WT (ATP) group vs WT (AZ+ATP) group). (Statistical analysis of the results was performed one-way ANOVA analysis followed by Dunnett’s multiple comparisons test or Tukey’s multiple comparisons test).