In summary, our results demonstrate an improvement in the analgesic properties of MOR and DOR agonists after their co-administration with slow-releasing H2S donors in animals with neuropathic pain, and suggest that these effects could be explained by the peripheral up-regulation of MOR and DOR, and the activation of the endogenous opioid system induced by DADS and GYY4137. This evidence concerns the gene OPRM1 and neuropathic pain.