Intrathecal administration of CGRP_8-37 reduces mechanical hypersensitivity specifically in female mice in three pain models. A, Animals received a single intrathecal injection of 1 μg of CGRP_8-37 immediately before an intraplantar injection of 0.1 ng of IL-6r. Once initial hypersensitivity to intraplantar injection of IL-6r had resolved, animals received a second intraplantar injection of 100 ng of PGE₂ (n = 8 mice/group). B, Animals received an intraplantar injection of 0.1 ng of IL-6r and then 7 d later an injection of 100 ng of PGE2. Immediately before the PGE₂ injection, animals received an intrathecal injection of 1 μg of CGRP_8-37 (n = 7–8 mice/group). C, Animals were given a hindpaw incision and an intrathecal injection of 1 μg of CGRP_8-37 at the time of incision and then 24 h postincision. After the initial hypersensitivity following the incision had returned to baseline levels, animals received an intraplantar injection of 100 ng of PGE₂ to test for hyperalgesic priming (n = 5–6 mice/group). D, Mice were given an SNI surgery and then a single intrathecal injection of 1 μg of CGRP_8-37 21 d after initial injury (males, n = 3 mice/group; females, n = 4 mice/group). NP, Neuropathic pain. Differences between groups were measured using a two-way ANOVA with Bonferroni's post hoc test: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.