الفهرس 
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Abstract
Background and Aim: Diabetes and its complication increasingly have become a major health problem facing the whole world. Peripheral diabetic neuropathy (DN) is regarded one of the most common diabetic chronic microvascular complications. Multiple domains contribute to the pathogenesis of DN including the inflammatory as well as the vascular pathways.There is a degree of interaction between the diabetic microvascular changes and the undergoing inflammatory process. This interaction was found to be more prominent in painful DN. Thus, several drugs which were able to improve either pain behavior or nerve conduction velocity (NCV) act through either the inflammatory or the microvascular etiopathogenesis. The present study aimed to investigate the potential neuroprotective effect of pentoxifylline (PTX) administration (50, 100 and 200mg/kg) in DN as regard therapeutic targeting of both the inflammatory and the vascular changes affecting peripheral nerves. In addition, it evaluates the anti-allodynic effect of PTX in diabetic neuropathic pain (DNP).
Methods: The animal model of DN was induced by intraperitoneal injection of a single dose (50mg/kg) of STZ. Rats were divided into the eight groups (n=12 for each group, n=10 for naïve group). The groups were naïve, control, PTX (50, 100 and 200) early and late groups. Blood glucose levels, body weight and mechanical allodynia were measured weekly for eight weeks. At the end of the 8th week, rats were sacrified. Sciatic nerves conc. of tumor necrosis factor-alpha (TNFα) and vascular endothelial growth factor (VEGF) were analyzed using ELISA technique. Sciatic nerves cross sections were stained with intercellular adhesion molecule-1 (ICAM-1) antibodies for analysis of ICAM-1 positively stained vessels. Histological examination of sciatic nerves and footpad epidermal thickness were done.
Results: STZ induced DN caused a significant increase in blood glucose level, failure to gain weight, significant increase in sciatic content of TNFα, VEGF and ICAM-1 positively stained vessel as well as alteration of the normal architecture of sciatic nerves and footpad with a decrease in footpad epidermal thickness, This changes were improved in PTX early and late groups, except for the hyperglycemic state and failure to gain weight. The STZ- induced mechanical allodynia improved in PTX 100, 200 early and PTX 200 late groups.
Conclusions:Despite failure of PTX to improve the glycemic control in diabetic rats, there was decrease in DNP evidenced by the improvement in mechanical allodynia. Additionally, PTX improved the existing pathogenesis as regard the inflammatory cascade as evidenced by TNF-α inhibition and endoneurial hypoxic state as evidenced by the decreased VEGF. So, this proved the efficacy of PTX in treatment of diabetic neuropathy. Moreover, early treated groups showed more pronounced effect than late treated groups on mechanical allodynia, sciatic content of TNFα, VEGF and footpad epidermal thickness.