Efficacy and safety of combined low doses of either diclofenac or celecoxib with gabapentin versus their single high dose in treatment of neuropathic pain in rats

Abstract

Neuropathic pain is a worldwide health problem with no consensus regarding its optimal therapy. This study compared the analgesic effect and gastric, hepatic, and renal safety of combined low doses of diclofenac and celecoxib with gabapentin versus their individual high doses in the treatment of neuropathic pain in rats. Left sciatic nerve ligation was used as neuropathic pain model. Rats were allocated into 7 groups (7 rats for each): sham control; model group (received vehicle); Gaba-group (received gabapentin (100 mg/kg /day); Diclo 10-group (received diclofenac (10 mg/kg); Cele 10-group (received celecoxib (10 mg/kg/day); Gaba + Diclo 5 (receivedgabapentin(100 mg/kg /day) plus diclofenac (5 mg/kg); Gaba + Cele 5 (received gabapentin (100 mg/kg/day) plus celecoxib (5 mg/kg)). The analgesic effect was assessed using both hot plate and acetone tests. The impact of the used drugs on peptic ulcer index, liver enzymes, and serum urea and creatinine was evaluated, along with histopathological examination and oxidative stress parameters. Combination therapy of low dose of either diclofenac or celecoxib, with gabapentin showed higher analgesic effect compared with their individual high doses as indicated by prolonged response time in hot plate test and decreased frequency of paw withdrawal in acetone test. Their effect was associated with gentle effect on gastric mucosa, renal and hepatic integrity and oxidative stress parameters. In conclusion, the use of combined low doses of either diclofenac or celecoxib with gabapentin is better than high dose monotherapy regarding both the efficacy and safety.