Systemic dermorphin [d-Arg2, Lys4] (1–4) amide (DALDA) selectively inhibits the C-component of wide-dynamic range (WDR) neurons to electrical stimulation, an effect that is blocked by methylnaltrexone bromide (MNTX). (A) An analog recording of WDR neuronal responses to the 1st, 4th, 8th, and 16th stimulus of a train of intracutaneous electrical stimuli (0.5 Hz, 16 pulses, 2.0 ms, supra-C-fiber activation threshold) that induces windup. WDR neuronal responses display A- and C-components to an intracutaneous electrical stimulus. At 2 to 3 weeks after spinal nerve ligation (SNL) in male rats, windup of C-component was inhibited at 30 to 45 min after systemic administration of DALDA (10 mg/kg, intraperitoneally). (B) The total A-component and C-component to graded intracutaneous electrical stimuli (0.1 to 10 mA, 2.0 ms) and the total C-component to windup-inducing stimuli after treatment of SNL rats with saline (intraperitoneally, n = 10), DALDA (10 mg/kg, intraperitoneally, n = 13), and MNTX (5 mg/kg, intraperitoneally, 15-min pretreatment, n = 9) followed by DALDA (10 mg/kg). **P < 0.01 versus saline group, one-way ANOVA. (C) The stimulus-response (S-R) function of the A-component of WDR neuronal response to graded intracutaneous electrical stimuli (0.1 to 10 mA, 2 ms) before and 30 to 45 min after systemic injection of DALDA (upper, 10 mg/kg, n = 9, intraperitoneally) or MNTX (5 mg/kg, intraperitoneally, 15-min pretreatment) with DALDA (lower, 10 mg/kg, n = 8, intraperitoneally). (D) The S-R function of C-component to graded intracutaneous electrical stimuli in each group. (E) Windup of C-component of WDR neurons to a train of intracutaneous electrical stimuli (0.5 Hz, 16 pulses) before and after drug treatment. The C-component to 0.5 Hz stimulation was plotted against the stimulation sequence number of each trial. (C–E) *P < 0.05 versus predrug, two-way repeated measures ANOVA. Data are expressed as mean ± SEM.