Fig. 4

Tolerance to the antinociceptive effects of fentanyl is not blocked by SP600125. JNK inhibition attenuates chronic tolerance to the hypothermic but not the antinociceptive effects of repeated treatment with fentanyl (0.3 mg/kg). Wild-type mice were treated with vehicle (black line with triangles), 3 mg/kg SP600125 (dashed black line with diamonds), or 10 mg/kg SP600125 (black line with diamonds) 60 min prior to administration of fentanyl (0.3 mg/kg) for ten consecutive days. Tail-flick antinociception (a), hotplate nociception (b), and body temperature (c) were measured 60 min later. Treatment with only SP600125 (3 mg/kg) attenuated tolerance to the hypothermic effects of chronically administered 0.3 mg/kg fentanyl alone. Data are expressed as mean ± S.E.M. (n = 10–24 per group). *p < 0.0001 for SP600125 (3 mg/kg) vs. vehicle or SP600125 (10 mg/kg) groups (ANOVA, Bonferroni post hoc)