Background: Uncoupling protein 2 (UCP2) is an intramembranous mitochondrial protein that the knocking down of its gene causes an induction of the pro-inflammatory responses. However, genipin, as a pharmacological inhibitor of UCP2, has anti-inflammatory effects. In this study the effect of genipin on rat paw inflammatory edema induced by formalin in the presence and absence of morphine was investigated.

Materials and Methods: In this research, male Wistar rats (200-250g) were assigned to seven groups: Saline(i.p)-Saline(i.t), Saline(i.p)-DMSO(i.t), Saline(i.p)-genipin(i.t), Morphine (10mg/kg,i.p)-DMSO(i.t), Morphine(10mg/kg,i.p)-genipin(i.t), Morphine(1μg/kg,i.p)-DMSO(i.t) and Morphine(1μg/kg,i.p)-genipin(i.t). Inflammation was induced in the rat’s hind paw by the injection of 50 µl of formalin 2.5% and paw volume was measured using plethysmometer method before and after the injection.

Results: Results revealed an anti-inflammatory effect for genipin against the formalin-induced paw edema (P<0.001). Genipin potentiated the anti-inflammatory effects of morphine, whereas it had no effect on pro-inflammatory effects of low dose of morphine this dose of morphine reversed the anti-inflammatory effects of genipin.

Conclusion: Although genipin, a UCP2 inhibitor, was expected to increase the inflammatory edema, but probably its anti-inflammatory effects via the NF-κB inhibition is so robust that can cover its inhibitory effect on UCP2 and the subsequent inflammation. The anti-inflammatory effect of morphine was set in the range of anti-inflammatory effects of genipin. The finding that the anti-inflammatory effect of genipin is attenuated at the presence of ultra-low dose morphine may be due to their common mechanisms which suggest further research on KATP channels.