The Role of the Inflammatory and the Vascular Pathogenesis in a Model of Streptozotocin Induced Diabetic Neuropathy in Rats

Abstract

Abstract Background Peripheral diabetic neuropathy (DN) is one of the major health problems facing the whole world. There is no treatment that could completely reverse or prevent progression of DN except for good glycemic control. The inflammatory and vascular pathways are two main domains that are incorporated in the pathogenesis of diabetic neuropathic pain (DNP) and DN. Thus, targeting both of them could be an appropriate way to delay progression of DN. Aim To investigate the role of the inflammatory and the vascular pathogenesis in diabetic mechanical allodynia. Method Twenty male Wistar rats were divided randomly into naïve and diabetic groups (n = 10). Diabetes was induced through i.p injection of single dose of streptozotocin (STZ) (50mg/kg), then 8 weeks after induction of diabetes, the sciatic content of tumor necrosis factor alpha (TNFα) and vascular endothelial growth factor (VEGF) was assessed using ELISA technique. Additionally, the number of intercellular adhesion molecule-1 (ICAM-1) as well as CD31, the most specific vascular marker, positively stained vessels was counted manually in sciatic nerves cross sections. Whereas, DNP was assessed weekly throughout the experiment using 60%mechanical threshold of paw withdrawal test. Results There was a significant increase in the sciatic content of TNFα, VEGF and ICAM-1 positively stained vessels and a significant decrease in CD31 positively stained vessels in the diabetic group as compared to the naïve group. There was a correlation between TNFα, VEGF, ICAM-1, CD31 positively stained vessels in one side and the 60% mechanical threshold on the other side (r=-0.8, -0.9, -0.8 and 0.7 respectively). Conclusion The diabetic mechanical allodynia is negatively correlated to the sciatic nerve content TNFα, VEGF, ICAM-1 and positively correlated to the CD31.