CGRP reduces Cl^– extrusion capacity in spinal dorsal horn neurons of female mice. A, I–V plots of a representative neurons of each experimental group. Insets, Electrophysiological traces of the currents generated by 500 μmol muscimol puffs at different holding voltage steps (93–30.5 mV). Calibration: 300 pA, 100 ms. B, KCC2 activity in laminae I and II neurons was estimated from the GABA_A I–V curve under 29 mm Cl^– load. Incubation of spinal cord slices with 50 ng/ml CGRP for >2 h induced a depolarization of E_GABA only in female tissue (n = 11–12 neurons/group). C, Male and female mice received an intrathecal injection of 130 μmol CLP257 immediately before intrathecal injection of 0.1 nmol CGRP. Mechanical hypersensitivity was measured using von Frey filament testing (n = 4 animals/group). Differences between groups were measured using a two-way ANOVA with Bonferroni's post hoc test: **p < 0.01, ***p <0.001, ****p < 0.0001.