Fig. 1

Procyanidins suppressed acute and chronic morphine tolerance via inhibiting microglia in the spinal cord. Tail-flick method was performed to evaluate the effect of procyanidins on the morphine tolerance. Data (n = 8) were shown as percentage of maximal possible effect (% MPE). a Procyanidins suppressed acute morphine tolerance. Before the treatment of morphine (10 mg/kg, s.c.), mice were pre-treated with different doses of procyanidins (i.g.) for 15 min. MPE was measured after morphine 10 mg/kg (s.c.) administration at the first day. b Procyanidins suppressed chronic morphine tolerance. Morphine was injected subcutaneously twice a day, and the MPE was measured 0.5 h after the first injection of each day. Before the treatment of morphine (10 mg/kg, s.c.), mice were pre-treated with different doses of procyanidins (i.g.) for 15 min. c Procyanidins inhibited morphine-induced upregulation of IBA-1 and phosphorylation of p38 MAPK, but not the p38 total protein. Samples were obtained and analyzed 2 h after morphine treatment on day 7. Representative western blot data (n = 4) for p-p38, p38, and IBA-1 was shown. d Immunofluorescence images and analysis showed the activation of microglia after morphine injection (n = 4) in the spinal cord. *p < 0.05, **p < 0.01, ***p < 0.001 vs. baseline; ^# p < 0.05, ^## p < 0.01 vs. morphine-treated group. Scale bar 75 μm