The Effect of L-NAME and Celecoxib on Diabetic Neuropathy in Rats

Background: Diabetic neuropathy (DN) is known as the most troublesome of diabetes mellitus complications. There is a cross-talk between cyclooxygenase-2 (COX-2) and the enzyme NO synthase (NOS) in pain pathophysiology in the dorsal root ganglia and the spinal cord. This study aimed to determine the possible role of the NOS inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME), or the COX-2 inhibitor, celecoxib, alone and in interaction with each other, on hyperalgesia and allodynia in rats with DN. Methods: Streptozotocin (STZ) (60 mg/kg, IP, once) was used to induce diabetes in male Wistar rats. After 72 hours, the animals were divided into groups that received celecoxib (5 mg/kg), L-arginine (L-ARG) (50 mg/kg), or L-NAME (50 mg/kg) alone and two groups that received a combination of celecoxib with either L-ARG or L-NAME. The von Frey and acetone tests were used to evaluate hyperalgesia and allodynia 14 days after treatment. Results: A significant increase in the withdrawal threshold level was observed in the groups receiving celecoxib alone (P<0.001) and in combination with L-ARG (P<0.001) or L-NAME (P<0.001). The reaction percentage in the acetone test significantly decreased in the celecoxib, L-NAME, celecoxib+L-ARG, and celecoxib+L-NAME groups (P<0.001) compared with the diabetic control group. Conclusion: The main finding was that inhibiting COX-2 and NOS reduced hyperalgesia and mechanical allodynia in diabetic rats. Also, the results revealed that there is cross-talk between these two enzymes.