The experimental schedule of MOR-KO mice. Before microinjection of the dsAAV vectors (pre; 0 day), the antinociceptive effects of saline, morphine (M10; 10 mg/kg, s.c.), and naloxone (Nx10; 10 mg/kg, s.c.) were tested by tail-flick test (TF) as the pretest data. After dsAAV injections, the mice (n = 12) were tested with either Nx10 (s.c., on 14th day) or M10 (s.c., on 21th day). The AUC values of tail-flick test were calculated respectively. Mice were then separated into 2 groups (n = 6) and injected with either M10 (s.c., b.i.d) or Nx10 (s.c., b.i.d.) for 4 days. The ED50 of the drugs were evaluated before and after the sub-chronic drugs treatment.