Sesamol Suppresses Neuro-Inflammatory Cascade in Experimental Model of Diabetic Neuropathy

Development of tolerance, inadequate relief, and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve diabetic neuropathic pain. The aim of the present study was to explore the effect of sesamol on thermal and mechanical hyperalgesia, allodynia, oxidative-nitrosative stress, inflammation, and apoptosis in STZ-induced experimental diabetes. Diabetic rats developed neuropathy, which was evident from a marked hyperalgesia and allodynia associated with enhanced nitrosative stress, release of inflammatory mediators (TNF-alpha, IL-1 beta, TGF-1 beta), and caspase 3. Chronic treatment with sesamol (2, 4, and 8 mg/kg body weight; po) for 4 weeks starting from the 4th week of STZ injection significantly attenuated behavioral, biochemical, and molecular changes associated with diabetic neuropathy. Moreover, diabetic rats treated with insulin-sesamol combination produced more pronounced beneficial effect as compared to their per se groups. The major finding of the study is that insulin alone corrected the hyperglycemia and partially reversed the pain response in diabetic rats. However, the combination with sesamol not only attenuated the diabetic condition but also reversed neuropathic pain through modulation of oxidative-nitrosative stress, inflammatory cytokine release, and caspase-3 in diabetic rats, and thus it may find clinical application to treat neuropathic pain in the diabetic patient. Perspective: This study shows the beneficial effect of sesamol on neuropathic pain through modulation of oxidative-nitrosative stress, inflammatory cytokine release, and caspase-3 in diabetic rats, and thus it may find clinical application to treat neuropathic pain in the diabetic patient. (C) 2010 by the American Pain Society