![Figure 6. The P2Y6 receptor mediated effects of PGE2-G in HbSS-BERK mice. (A) A single systemic injection of the P2Y6 receptor antagonist, MRS2578 (30 nmol/50 μL, intraperitoneally), reduced mechanical allodynia in HbSS-BERK mice over time (2-way ANOVA for repeated measures (F[5, 45] = 2.65; P = .035, N = 7 mice per group). *Different from baseline (BL) in HbSS-BERK mice at P ≤ .038. #Different from HbAA-BERK mice at P ≤ .013; Bonferroni t test. The dose of MRS2578 that suppressed allodynia in HbSS mice did not change mechanical threshold in HbAA mice (P = 1.0, N = 5, Bonferroni t test). Legend in panel A is common to panel B. (B) Intraplantar injection of MRS2578 (10 nmol/10 μL, intraplantarly) blocked mechanical allodynia in HbSS-BERK mice acutely (2-way ANOVA for repeated measures; F[4, 36] = 3.39; P = .019, N = 7 mice per group). *Different from BL in HbSS-BERK mice at P ≤ .005. #Different from HbAA-BERK mice at P ≤ .017; Bonferroni t test. MRS2578 had no effect in HbAA mice (P ≥ .60, N = 4, Bonferroni t test). (C) Intraplantar injection of PGE2-G (2.3 nmol/10 μL, intraplantarly) produced mechanical allodynia in C3H mice and this effect was blocked by coinjection of the P2Y6 receptor antagonist, MRS2578 (3 nmol); 2-way ANOVA for repeated measures (F[3, 84] = 56.59; P > .001). *Different from BL within PGE2-G and from vehicle (ratio of DMSO to ethanol to saline, 0.7%:5%:94.3%) at P ≤ .003, N = 8-6 mice per treatment. #Different from PGE2-G plus MRS2578 at P ≤ .007, N = 6 mice per treatment, Bonferroni t test. MRS2578 alone had no effect (P = 1.0, N = 5, Bonferroni t test). Legend in panel C is common to panel D. (D) PGE2-G (2.3 nmol/10 μL, intraplantarly) increased sensitivity to radiant heat in C3H mice as defined by a decrease in PWL. Coinjection of MRS2578 (3 nmol) suppressed heat hyperalgesia produced by PGE2-G (2-way ANOVA RM (F[3, 52] = 9.97; P = .001, N = 5-8 mice per treatment). *Different from BL within PGE2-G–treated group and from vehicle at P ≤ .009. #Different from PGE2-G plus MRS2578 treatment at P ≤ .035, N = 6, Bonferroni t test. MRS2578 alone had no effect (P = .69, N = 5, Bonferroni t test).](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/133/18/10.1182_blood-2018-11-884346/3/blood884346f6.png?Expires=1724240349&Signature=toaHdwAeLBa7MuMCDbYPt~SIt39QJ1KLBmZ2VVTEhLC0PsMo~3wtiVkLzUsWIEfdrsrgqzGpHThyLZoR9rQRxviJ~5YWeHGN1plKADo5SmRlC4tOM9H8A8KKW6rw5mpOuHtV6IoqtQVJYf-60DPUj90v7mMSGuPGJuxqN7R1R2-MY~qBscO1hrtpGfHCE6GlWzHMq5MfLUblRPO3DCE6Ds0C6QJalqPpss07GXHhtL6G5KcjM~COzoCkEqWWMgT15onaGtmuNvHvQUpEDAxgXRpqAXqm6NyOm91K82wuYHS6wKXcNFlOTco~95XMsgVFFNMmPKOddWweY0JCBZAKPg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
The P2Y6 receptor mediated effects of PGE2-G in HbSS-BERK mice. (A) A single systemic injection of the P2Y6 receptor antagonist, MRS2578 (30 nmol/50 μL, intraperitoneally), reduced mechanical allodynia in HbSS-BERK mice over time (2-way ANOVA for repeated measures (F[5, 45] = 2.65; P = .035, N = 7 mice per group). *Different from baseline (BL) in HbSS-BERK mice at P ≤ .038. #Different from HbAA-BERK mice at P ≤ .013; Bonferroni t test. The dose of MRS2578 that suppressed allodynia in HbSS mice did not change mechanical threshold in HbAA mice (P = 1.0, N = 5, Bonferroni t test). Legend in panel A is common to panel B. (B) Intraplantar injection of MRS2578 (10 nmol/10 μL, intraplantarly) blocked mechanical allodynia in HbSS-BERK mice acutely (2-way ANOVA for repeated measures; F[4, 36] = 3.39; P = .019, N = 7 mice per group). *Different from BL in HbSS-BERK mice at P ≤ .005. #Different from HbAA-BERK mice at P ≤ .017; Bonferroni t test. MRS2578 had no effect in HbAA mice (P ≥ .60, N = 4, Bonferroni t test). (C) Intraplantar injection of PGE2-G (2.3 nmol/10 μL, intraplantarly) produced mechanical allodynia in C3H mice and this effect was blocked by coinjection of the P2Y6 receptor antagonist, MRS2578 (3 nmol); 2-way ANOVA for repeated measures (F[3, 84] = 56.59; P > .001). *Different from BL within PGE2-G and from vehicle (ratio of DMSO to ethanol to saline, 0.7%:5%:94.3%) at P ≤ .003, N = 8-6 mice per treatment. #Different from PGE2-G plus MRS2578 at P ≤ .007, N = 6 mice per treatment, Bonferroni t test. MRS2578 alone had no effect (P = 1.0, N = 5, Bonferroni t test). Legend in panel C is common to panel D. (D) PGE2-G (2.3 nmol/10 μL, intraplantarly) increased sensitivity to radiant heat in C3H mice as defined by a decrease in PWL. Coinjection of MRS2578 (3 nmol) suppressed heat hyperalgesia produced by PGE2-G (2-way ANOVA RM (F[3, 52] = 9.97; P = .001, N = 5-8 mice per treatment). *Different from BL within PGE2-G–treated group and from vehicle at P ≤ .009. #Different from PGE2-G plus MRS2578 treatment at P ≤ .035, N = 6, Bonferroni t test. MRS2578 alone had no effect (P = .69, N = 5, Bonferroni t test).