Systemic dermorphin [d-Arg2, Lys4] (1–4) amide (DALDA) retains ability to inhibit mechanical hypersensitivity in nerve-injured rats that receive resiniferatoxin (RTX). (A) The paw withdrawal latency (PWL) of the ipsilateral hind paw was significantly decreased in male rats on day 7 after spinal nerve ligation (SNL; pre-RTX). On days 7 to 9 after intraperitoneal injection of RTX (0.1 mg/kg, n = 9), both ipsilateral and contralateral PWLs were significantly increased from the pre-RTX and preinjury level. (B) Rats showed significant reduction in ipsilateral paw withdrawal thresholds on day 7 post-SNL. Systemic RTX treatment (0.1 mg/kg, intraperitoneally, n = 9) did not alter SNL-induced mechanical allodynia. However, systemic administration of DALDA (10 mg/kg, subcutaneously) significantly attenuated mechanical allodynia even after RTX treatment. *P < 0.05 versus preinjury, #P < 0.05 versus pre-RTX, one-way repeated measures ANOVA. Data are expressed as mean ± SEM.