α2δ-1 is essential for the chronic morphine exposure–induced activation of presynaptic N-methyl-d-aspartate receptors in the spinal dorsal horn. (A) Representative recording trace and cumulative plots show the effect of bath application of 50 μM 2-amino-5-phosphonopentanoic acid (AP5) on the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) of a lamina II neuron from a morphine-treated wild-type (WT) mouse. (B) Summary data show the effect of 50 μM AP5 on the mean frequency and amplitude of mEPSCs (n = 11 neurons) in spinal cord slices from morphine-treated WT mice. (C) Representative recording traces and cumulative plots show no effect from AP5 on the frequency or amplitude of mEPSCs of a lamina II neuron from a morphine-treated α2δ-1 knockout (KO) mouse. (D) Summary data show no effect of AP5 on the mean frequency or amplitude of mEPSCs (n = 10 neurons) in spinal cord slices from morphine-treated α2δ-1 KO mice. The data are shown as means ± SD. ***P < 0.001 versus the baseline. ##P < 0.01 versus the baseline in the WT group.