Co-administration of Epalrestat and Sitagliptin attenuate development and existing pain in a rat model of neuropathic pain: Role of anti-inflammatory and antioxidative effects

Neuropathic pain is one of the most important consequences of nerve damage, manifesting itself as various demonstrations, including hyperalgesia and allodynia. The present study aimed to investigate the effect of concomitant use of Epalrestat and Sitagliptin on pain reduction in the chronic constriction injury (CCI) model in rats through anti-inflammatory and antioxidant effects.

The present study was conducted on a total of 50 male rats that were randomly assigned to five groups: sham, CCI, CCI+Epalrestat(100 mg/kg, IP injection, for 14 days), CCI+Sitagliptin(10 mg/kg, IP injection, for 14 days), and CCI+Epalrestat(100 mg/kg)+Sitagliptin(10 mg/kg). Rats underwent behavioral tests on days 4, 7, and 14 after the surgery. After 14 days, the spinal cord was collected to measure anti-inflammatory and antioxidant tissue concentrations.

The results of this study demonstrated that simultaneous injection of these two drugs in group 5 had the most neuroprotective effect, compared to that in groups 3 and 4. The results of dynamic responses to mechanical stimulation on the 14th day illustrated that there was no significant difference in groups 3 and 4 . Nonetheless, in Group 5, a significant difference was detected in all factors. The results pointed out that the combined use of Epalrestat and Sitagliptin decreased the levels of Tumor necrosis factor, Interleukin 6, and MDA, and also increased the level of glutathione peroxidase

As evidenced by the obtained results, the concomitant use of Epalrestat and Sitagliptin can be considered effective and safe for the treatment of neuropathic pain with strong inhibition of inflammatory factors and oxidative stress.