In conclusion, this study reports for first time that SFN treatment reverses mechanical allodynia and enhances the antinociceptive effects of DOR agonists by normalizing Nrf2, NQO1 and DOR down-regulation, increasing HO-1 expression, reducing hyperglycemia and inhibiting JNK phosphorylation in the sciatic nerve of diabetic mice. Here, MAPK8 is linked to Hyperglycemia.