The effect of intrathecal administration of Genipin on rat paw inflammatory edema in the presence and absence of morphine

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. 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 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. 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.