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Abstract Background:Diabetic neuropathy (DN) is the most common complication of diabetes. Ibuprofen-L-arginine exerts antinociceptive effects on both mechanical and cold allodynia induced by chronic constriction injury (CCI) and L-Arginine alone exerted antinociceptive effects on cold allodynia in CCI. The aim of the work:was toassess the antinoceceptive effect of ibuprofen and L-arginine in a rat model of diabetic neuropathy and to further investigate the role of spinal miR-155 TNF alpha and NO in this effect. Methods: Type 1 DM was induced in rats by STZ. Assessment of mechanical allodynia was carried out weekly by von Frey filaments. Drugs were administered daily by gastric gavage for 4 weeks starting one week after STZ injection. At the end of the fourth week, spinal miRNA-155 expression and TNF alpha and NO levels were assessed. Footpad epidermal thickness and soleus muscle fiber diameter were quantified by image analysis. Results: Ibuprofen and L-arginine and their combination resulted in a significant decrease of the tactileallodyniaby thefifth week of the experiment. These findings run in accordance with the histological studies of muscle fiber diameter & epidermal thickness. Further, there were significant increase in the spinal NO level and miRNA-155 in STZ induced diabetic group. Both ibuprofen and L-Arginine and their combination showed a significant decrease of both the behavioural and biochemical tests. Only ibuprofen reduced spinal TNF alpha level. Conclusion: Both ibuprofen and L-arginine resulted in a behavioural and histological improvement of DN, with concomitant suppression of spinal miR-155 and NO level |