Comparison of the Effects of Zonisamide, Ethosuximide and Pregabalin in the Chronic Constriction Injury Induced Neuropathic Pain in Rats

Abstract

Background: Evidence has been generated that various anticonvulsant agents provide relief of several chronic pain syndromes and therefore as an alternative to opioids, nonsteroidal anti.inflammatory, and tricyclic antidepressant drugs in the treatment of neuropathic pain. The results of these studies thus raise the question of whether all anticonvulsant drugs or particular mechanistic classes may be efficacious in the treatment of neuropathic pain syndromes.

Aim: The aim was to compare the clinically used anticonvulsant drugs which are differ in their mechanism of action in a chronic pain model, the chronic constriction injury, in order to determine if all anticonvulsants or only particular mechanistic classes of anticonvulsants are analgesic.

Materials and Methods: The study included zonisamide, ethosuximide and pregabalin. All compounds were anticonvulsant with diverse mechanism of actions. The peripheral neuropathic pain was induced by chronic constriction injury of the sciatic nerve in male Sprague.Dawley rats. Zonisamide (80 and 40 mg/kg), ethosuximide (300 and 100 mg/kg), pregabalin (50 and 20 mg/kg), and saline was administered intraperitoneally in respective groups in a blinded, randomized manner from postoperative day (POD) 7.13. Paw withdrawal duration to spontaneous pain, chemical allodynia and  mechanical hyperalgesia and paw withdrawal latency to mechanical  allodynia and thermal hyperalgesia were tested before drug administration on POD7 and after administration on POD 7, 9, 11 and 13.

Results: The present study suggests that these drugs could provide an effective alternative in the treatment of neuropathic pain. However, zonisamide and pregabalin appears to have suitable efficacy to treat a wide spectrum of neuropathic pain condition.

Conclusion: The present findings suggest that the inhibition of N.type calcium channels or voltage.gated sodium and T.type calcium channels provides better analgesic potential instead of inhibition of T.type calcium channels alone.

Keywords: Chronic constriction injury model, Ethosuximide, Neuropathic pain, Pregabalin, Zonisamide