Carrageenan- and IL-6-induced hyperalgesic priming is reduced in male, but not female, DRD5KO mice. A, IL-6 injection induces mechanical hypersensitivity in male WT and DRD5KO mice that lasts for at least 48 h. N = 6 mice per group. B, Subsequent injection of PGE2 reveals hyperalgesic priming in male WT mice less in DRD5KO mice. N = 6 mice per group. C, Similarly, IL-6 failed to induce an increase in the mouse grimace scores in DRD5KO mice at 3 h. N = 6 mice per group. D, Finally, DRD5KO mice exhibit a significant reduction in MGS scores compared with WT mice after injection of PGE2 at 3 and 24 h. N = 6 mice per group. E, Intrathecal injection of carrageenan (1%) produces a strong mechanical hypersensitivity in male WT mice that is significantly reduced in DRD5KO mice. F, Moreover, PGE2-induced mechanical hypersensitivity is observed in primed DRD5KO mice. N = 6 mice per group. G, Intrathecal injection of carrageenan produces a robust mechanical hypersensitivity in female WT and DRD5KO mice that lasted for 72 h. N = 5 or 6 mice per group. H, Injection of PGE2 reveals the presence of priming in both genotypes. N = 6 mice per group. I, Carrageenan-induced thermal hypersensitivity is significantly attenuated in male DRD5KO mice at 48 h. N = 5 or 6 mice per group. J, However, the size of the edema is comparable between WT and DRD5KO mice. N = 6 mice per group. K, Carrageenan-induced thermal hypersensitivity is similar between WT and DRD5KO female mice. N = 6 mice per group. L, Yet, a significant increase in the size of the edema in the female DRD5KO mice was observed 24 h after treatment. N = 6 mice per group. M, Changes in paw temperature as a measure of inflammation observed in the left paw injected with carrageenan compared with the right paw. N, Carrageenan induces a significant increase in temperature of the ipsilateral compared with the contralateral paw at 3 h, but not at 24 h. N = 12–14 per group. O, No differences were observed in the temperature of the injected paw between WT and DRD5KO mice at 3 and 24 h. *p < 0.05, comparing WT versus DRD5KO (two-way ANOVA with Bonferroni post hoc test). **p < 0.01, comparing WT versus DRD5KO (two-way ANOVA with Bonferroni post hoc test). #p < 0.05, compared with baseline (two-way ANOVA with Bonferroni post hoc test).