Role of PI3K/Akt signal pathway in diabetic neuropathic pain in rats*

Objective To investigate the role of PI3K/Akt signal pathway in diabetes neuropathic pain induced by streptozocin.Methods Wistar rats weighing 180-220g,Diabetes neuropathic pain was induced by intraperitoneal streptozocin 65mg/kg,and 64 rats with diabetic neuropathic pain were randomly divided into two groups:group Ⅱdiabetic neuropathic pain and group Ⅲ Ⅱ+PI3K inhibitor,while 32 age matched rats were used to be group Ⅰ control.Then rats were group housed with full access to food and water.At the begin of fifth week,rats in group Ⅲ received Wortmannin,a selective PI3K inhibitor 0.5mg/kg intravenous from tail vein once a day,while the animals in groupⅠandⅡreceived vehicle only.At the end of the fourth,sixth,eighth and tenth week,Paw withdrawal mechanical threshold(MWT) were measured by a set of Von Frey filaments.The animals were anesthetized and nerve conduction velocity(NCV) of left sciatic nerve was measured.The animals were then killed and the lumbar segment of the spinal cord and dorsal root ganglion(DRG) were removed for determination of the level of p-Akt by immunohistochemistry and western blots.Results The MWT was significantly lower and NCV slower and the level of p-Akt in DRG and the spinal cord was significantly higher in groupⅡ than in groupⅠ at each time point.The selective inhibitor of PI3K significantly attenuated the above-mentioned diabetes induced changes in group Ⅲ.Conclusion The signal transduction pathway of PI3K/Akt is involved in the development of diabetic neuropathic pain in rats.