Fig. 1. Systemic loperamide attenuated neuropathic pain after L5 spinal nerve ligation (SNL).
(A) L5 SNL induced a decrease in PWT on the hindpaw ipsilateral to the injured side that lasted for 56 days. *P < 0.05 versus pre-SNL baseline (n = 8–12). (B) Vehicle or different doses of loperamide (n = 7–10) were injected subcutaneously in different groups of rats on day 7 post-SNL. Loperamide dose-dependently reversed mechanical allodynia that developed on the hindpaw ipsilateral to the SNL. *, $, # P < 0.05 versus the respective pre-drug baseline. (C) MPE (%) for loperamide to attenuate mechanical allodynia was calculated at 30 min post-injection for each dose, and a dose-response function was established accordingly. PWT data are presented as median values, and MPE data are expressed as means ± SEM. ++P < 0.01 versus the vehicle-treated group. (D) Systemic loperamide (1.5 mg/kg, n = 6, s.c.) also attenuated heat hyperalgesia that developed in the hindpaw ipsilateral to the SNL in rats on day 7 post-SNL, but did not affect PWL on the contralateral side. *P < 0.05 versus pre-drug baseline, #P < 0.05 versus the ipsilateral hindpaw.