Fig. 1
AICAR attenuates CFA-induced pain behavior and local inflammation and promotes phosphorylation of AMPK in mice. Effects of a single hypodermic injection of AICAR (5, 15, or 20 μg/20 μl) on mechanical allodynia (a) and thermal hyperalgesia (b) in CFA-injected mice. The panels show the hindpaw withdrawal threshold in response to mechanical stimulation as assessed with von Frey hairs in a or thermal stimulation as assessed with hot plate in b (data are expressed as mean ± SEM, n = 8 mice/group). Two-way ANOVA revealed a significant difference at *P < 0.05 vs. Control group and #P < 0.05 vs. CFA+VEH group. c, d Subcutaneous administration of AICAR (5, 15, or 20 μg /20 μl) activated AMPK in the inflamed skin tissues in a dose-dependent manner. One-way ANOVA revealed a significant difference at *P < 0.05 vs. Control group and #P < 0.05 vs. CFA+VEH group. e H&E staining. (e1) Control mice with no inflammation in the skin, (e2) inflammation with abundant lymphocytes and sparse neutrophilic granulocytes in an CFA mouse with hypodermic injection of vehicle (20 μl sterilized PBS, the vehicle of AICAR), and (e3) low-grade inflammation in an CFA mouse with hypodermic injection of AICAR (15 μg/20 μl). Scale bar represents 100 μm. Tissues were collected at 2 h after AICAR treatment for Western blotting and HE. The abbreviations used here are VEH (vehicle of AICAR, sterilized double steamed H2O) and AI (AICAR)