Anti-nociceptive potential of donepezil in oxaliplatin-induced peripheral neuropathy: An in vivo study in wistar rats

Objectives: Neuropathic pain is a chronic disorder detrimental to the quality of life. In patients on cancer chemotherapy, involvement of peripheral nerves commonly leads to algesia. Gabapentin is a standard treatment for neuropathic pain. Donepezil, a cholinesterase inhibitor exerts neuroprotective effects and is useful in neurodegenerative diseases. Present study aimed to determine whether donepezil alone or in combination with gabapentin enhances anti-nociceptive and neuroprotective effect on chemotherapeutically induced peripheral neuropathic pain. Materials and Methods: Thirty female Wistar rats were divided into five groups comprising six each. The control group was treated with saline and group 2 with oxaliplatin (active control). Oxaliplatin 4 mg/kg twice weekly intraperitoneally was used to induce neuropathic pain for 28 days in all groups other than the control. Group 3, 4, and 5 received gabapentin 60 mg/kg, donepezil 1.5 mg/kg orally, and a combination of gabapentin 25 mg/kg and donepezil 1.5 mg/kg, respectively. Neuropathic pain assessment was followed by estimation of oxidative stress markers and interleukin-6 from the harvested sciatic nerve sample. Results: A combination of donepezil with gabapentin had demonstrated superior analgesic effects, corroborated by histopathological findings and alterations in oxidative stress markers. Conclusion: Donepezil gabapentin combination may be more effective in preventing the oxaliplatin-induced neuropathy clinically, along with having a neuroprotective effect.