Antinociceptive effect of KGNOP1 and morphine after s.c. administration in the formalin test in mice. Groups of mice received s.c. saline (control) or different doses of KGNOP1 (A,C) or morphine (B,D) before an intraplantar injection of the formalin solution in the right hindpaw, and the duration of pain behavior was monitored for 60 min, determined as the amount of time (in seconds, sec) each animal spent licking, biting, lifting, and flinching the formalin-injected paw. Time-course of pain behavior of mice treated with KGNOP1 (A) and morphine (B). Dose-dependent antinociceptive effect of KGNOP1 and morphine during Phase I (C) and Phase II (D) of the formalin test. Effect of pre-treatment with naltrexone (2.6 µmol/kg s.c., -15 min) or SB-612111 (6.6 µmol/kg s.c., -30 min) on the antinociceptive effect of KGNOP1 (1.22 mg/kg) during Phase I (E) and Phase II (F) of the formalin test. Data are presented as the mean ± SEM (n = 6–8 mice per group). * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. saline group, one-way ANOVA followed by Dunnett’s post hoc test (C,D); *** p < 0.001 vs. saline group and #
p < 0.05 and ##
p < 0.01 vs. KGNOP1-treated group, unpaired t-test.