Systemic administration of peripherally acting μ-opioid receptor agonists induces conditioned place preference in nerve-injured rats. (A) Spinal nerve ligation (SNL) rats spent more time in a dermorphin [D-Arg2, Lys4] (1–4) amide (DALDA)-paired chamber after drug conditioning (10 mg/kg, subcutaneous, n = 9) than during the preconditioning test period. However, DALDA did not induce conditioned place preference in naive rats (n = 8). (B) In SNL rats, the difference score (postconditioning time minus preconditioning time) for the DALDA-paired chamber (n = 9) was significantly greater than that for the saline-paired chamber. (C) A lower dose of DALDA (5 mg/kg,subcutaneous, n = 8) also significantly increased the difference score for the DALDA-paired chamber in SNL rats, but not naive rats (n = 8). (D) Loperamide (5 mg/kg, subcutaneous, n = 8), another peripherally acting opioid, induced conditioned place preference in SNL rats. (E) The difference score for the loperamide-paired chamber was significantly greater than that for the vehicle-paired chamber. (F) SNL rats spent more time in chambers paired with gabapentin (60 mg/kg, intraperitoneal, n = 8) after drug conditioning than they did before conditioning. However, gabapentin did not induce conditioned place preference in naive rats (n = 8). (G) The difference score for the gabapentin-paired chamber was significantly greater than that for the saline-paired chamber. A, D, F: Two-way repeated measures ANOVA with Bonferroni post hoc test, *P < 0.05, **P < 0.01. B, C, E, G: Student’s t test, **P < 0.01, ***P < 0.001 versus saline-paired. Data are expressed as mean ± SD.