Intrathecal CGRP causes an increased response in female mice that is not blocked by systemic CGRP mAb but is blocked by systemic olcegepant. A, Female mice received an intrathecal injection of CGRP in half-log step increments of 0.1, 0.3, or 1 nmol rat α-CGRP (n = 2–4 mice/dose). B, Male mice received intrathecal injections of rat α-CGRP in the same doses as female mice (n = 2–4 mice/dose). C, Dose–response curve of male and female mice at 60 min post-intrathecal injection of CGRP. Six increasing doses of rat α-CGRP were administered to both males and females, as follows: 0.01, 0.03, 0.1, 0.3, and 1 nmol. Differences between slopes were determined using an ANCOVA: p-value = 0.0013 [F = 7.931 (df of the numerator = 2; df of the denominator = 39); n = 11 mice for female dose–response curve; n = 12 mice for male dose–response curve]. D, Female mice received an intraperitoneal injection of 20 mg/kg CGRP mAb, 20 mg/kg control mAb, or vehicle 24 h before intrathecal injection of 0.1 nmol rat α-CGRP, and mechanical hypersensitivity was measured following these intrathecal injections (n = 6 mice/group). E, Female mice received an intraperitoneal injection of 1 mg/kg olcegepant or vehicle 30 min before intrathecal injection of 0.1 nmol rat α-CGRP, and mechanical hypersensitivity was measured following these intrathecal injections (vehicle, n = 8; olcegepant, n = 5). Differences between groups were measured using a two-way ANOVA with Bonferroni's post hoc test: *p < 0.05, **p < 0.01. I.P., Intraperitoneal; I.T., intrathecal; veh, vehicle.