الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Background and aim: Diabetic neuropathy (DN) is a serious complication of diabetes. 20 to 30% of patients with DN suffer from neuropathic pain. This study was designed to investigate the role of early and late treatment of pentoxifylline (PTX) in management of diabetic neuropathic pain and possible mechanism involved in it. Method: Rats were divided into 8 groups: naïve group, diabetic control group, 3 PTX early treated groups in three different doses (50, 100 &200 mg/kg in drinking water, starting one week after STZ injection, for 7 weeks), and 3 PTX late treated in three different doses (50, 100 &200 mg/kg in drinking water, starting six week after STZ injection, for 2 weeks). Mechanical allodynia, body weight and blood glucose level were assessed weekly, microglia and astrocytes activation, spinal nuclear factor kB & tumor necrosis factor-α (TNF-α) and sciatic TNF-α were estimated at the end of the 8th week. Epidermal thickness of the food pad and Na+,K+-ATPase activity in sciatic nerve were measured. Results: The results suggested that activated microglia were involved in the development of experimental DN. PTX inhibited neuroimmune activation of microglia, reduce the levels of proinflammatory cytokines and improved epidermal thickness and Na+/K+-ATPase activity in sciatic nerve. Early 100, 200 and late 200 PTX groups showed antiallodynic effect. The antiallodynic of early PTX treated groups is more pronounced than the antiallodynic of late PTX treated groups. Conclusion: PTX is a fundamental drug whose antiallodynic effect depends on the pathogenic mechanisms and had the ability to inhibit the progression of the disease. Early PTX treatment showed more pronounced effect than late treatment on mechanical allodynia, sciatic TNF-α and epidermal thickness of the foot pad.