DOI: 10.5176/2345-783X_PHARMA17.31
Authors: Kanwaljit Chopra,Pratishtha Singh, Anurag Kuhad, Anil Kumar
Abstract:
Diabetes mellitus is a debilitating epidemic affecting all social strata, imposing huge health, social and economic burdens. Diabetic neuropathicpain,is the commonest microvascular complication of diabetes mellitus, characterized by allodynia and hyperalgesia, is recognized as one of the most difficult types of pain to treat. The development of tolerance, partial relief and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. Reactive oxygen/nitrogen species, cytokines and matrix metalloproteinases (MMP) are implicated in the pathogenesis of diabetic neuropathy. The present study was designed to explore the effect of naringenin, a citrus flavonoid in streptozotocin induced diabetic neuropathic pain in Wistar rats. After eight weeks of diabetes induction, animals developed neuropathy which was evident from a marked hyperalgesia and allodynia associated with enhanced nitrosative stress, a release of inflammatory mediators (TNF-α, TGF-1β), MMP-9 activation and decreased motor nerve conduction velocity. Treatment with naringenin (25, 50, 100 mg/kg) for four weeks starting from 5th week of streptozotocin injection significantly attenuated behavioral, biochemical and molecular changes, along with alterations in motor nerve conduction velocity in a dose-dependent manner. Moreover, diabetic rats treated with insulin-naringenin combination produced a more pronounced effect as compared to individual drugs. The key observations of this study revealed that the insulin alone amelioratedhyperglycemia and partially reversed the neuropathic pain. However, itscombination with naringenin not only attenuated the diabetic condition but also reversed neuropathic pain through modulation of oxidative–nitrosative stress, inflammatory cytokine release and MMP inhibition in the diabetic rats. Modulation of MMP9 by a natural flavonoid like naringenin seems to be a novel approach to target diabetic neuropathic pain.
Keywords: Diabetic neuropathic pain, Matrix metalloproteinase, Naringenin, Tumour necrosis factor alpha, Reactive oxygen species, Doxycycline
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