Effect of Pentoxifylline on Diabetic Neuropathic Pain in Rats

Abstract

Abstract Background and Aim Diabetic neuropathy (DN) is the most common diabetic complication, which has a lifetime prevalence of about 50%. About 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 (DNP). Method Diabetic rats were administered PTX (50 and 200 mg/kg/day, in drinking water) either one week after STZ injection and for 7 weeks or 6 weeks after STZ injection and for 2 weeks. Mechanical allodynia were assessed weekly, Iba-1 and GFAP immunorectivity, spinal NFκB & spinal sciatic TNF-α were estimated at the end of the study. Epidermal thickness of the food pad and Na+/K+-ATPase activity in sciatic nerve were measured as an outcome measure for predegenerative markers of DN. Results The results of the present study suggest that activated microglia and not astrocytes are involved in the development of experimental diabetic neuropathy. PTX inhibit neuroimmune activation of microglia, reduce the levels of proinflammatory cytokines and improve epidermal thickness of the food pad and Na+/K+-ATPase activity in sciatic nerve. Only PTX 200 mg/kg/day when administered early and late treatment in diabetic rats produced antiallodynic effect. Conclusion PTX is a fundamental drug whose antiallodynic effect depends on the pathogenetic mechanisms and has the ability to halt or inhibit the progression of the disease. The earlier the use of PTX in the developmental phase of mechanical hyperalgesia the more the antiallodynic effect of the drug.