Preventive effects of subcutaneous injection of d-amino acid oxidase inhibitors on morphine antinociception tolerance in formalin-induced acute nociception (A) and tonic pain (B). Mice received multiple bi-daily subcutaneous injections of saline (10 ml/kg), morphine (10 mg/kg), and the combination of morphine (10 mg/kg) and 5-chloro-benzo[d]isoxazol-3-ol (CBIO; 10 mg/kg), AS057278 (40 mg/kg), or sodium benzoate (400 mg/kg), respectively, for 7 days. The single injection of saline (10 ml/kg) or morphine (5 mg/kg) was made on the eighth day at 20 min before formalin challenge. Cumulated biting duration from 0 to 5 min and 20 to 40 min after formalin injection represented acute phase nociception and tonic phase pain, respectively. Data are presented as means ± SEM (n = 6 in each group). *, #, + Denote statistically significant difference from the saline + saline group, saline + morphine group, and morphine + morphine group, respectively (P < 0.05 by one-way ANOVA followed by post hoc Student–Newman–Keuls test).