Fig. 2.

κ-Opioid receptor antagonist norBNI reversed heroin withdrawal-induced hyperalgesia. (A) Male and female Wistar rats were handled and habituated to subcutaneous (SC) saline injections for 1 week before the baseline (BL) paw withdrawal threshold measurement. All of the rats then received subcutaneous heroin injections once per day, five times per week. After 2 weeks of heroin treatment, the rats were re-tested in the electronic von Frey test. On the following week, all of the rats received vehicle and were tested 30 min (Table S1) and 24 h later (Veh). Next, all of the rats received a single injection of norBNI (30 mg/kg, SC) and were tested at 30 min (Table S1) and 1, 4, 7, and 14 days post-norBNI. Importantly, after their single norBNI injection, the rats continued to receive their daily heroin treatment five times per week throughout the experiment. We tested hyperalgesia 4–6 h after the heroin injection (i.e., acute withdrawal). (B) nor-Binaltorphimine reversed opioid withdrawal-induced hyperalgesia in females up to 7 days. (C) A single norBNI treatment reversed opioid withdrawal-induced hyperalgesia in males up to 14 days. The data are expressed as mean ± SEM and were analyzed using one-way repeated-measures ANOVA followed by the Bonferroni post hoc test. *p < 0.05, difference from Veh (n = 7–9/group). gf, gram force.