Effects of Oxcarbazepine on Mechanical and Cold Allodynia in a Neuropathic Rat Model

Abstract

Background: It is well known that anticonvusant drugs such as carbamazepine are effective in the management of various neuropathic pain conditions. Oxcarbazepine, a keto analogue carbamazepine, might also be expected to have an analgesic effect because it is a derivative of carbamazepine. The aim of this study is to evaluate the analgesic effect of oxcarbazepine in a rat neuropathic pain model. Methods: Male Sprague-Dawley rats were prepared by tightly ligating the L5 and L6 spinal nerves to reproduce neuropathic pain. Sixty neuropathic rats were randomly assigned into 6 groups for the intraperitoneal administration of drugs. Normal saline, vehicle (polyethylene glycol 400), oxcarbazepine (10 mg/kg, 20 mg/kg, 30 mg/kg and 50 mg/kg) were administered respectively to the individual groups. We examined mechanical and cold allodynia preadministration, and 15, 30, 60, 90, 120, 150 and 180 min after intraperitoneal drug administration. Mechanical alladynia was quantified by measuring the withdrawal frequency to stimuli with two von Frey filaments of 35.6 mN and 115.2 mN. Cold allodynia was quantified by measuring the frequency of foot lift to 100% acetone. Pain behavior may be influenced by the adverse effects of anticonvulsants, which include sedation, motor incoordination. We therefore measured the locomotor function of the neuropathic rats by using the rotarod test. Results: The vehicle group showed no significant differences in the mechanical and cold allodynia versus the saline group. In the oxcarbazepine-treated groups, withdrawal frequencies to mechanical and cold stimuli were significantly reduced versus the pre-administration values and versus the vehicle group. The duration of antiallodynic effects increased dose-dependently, and these were maintained for 150 min at the highest dose. Only at the highest dose (50 mg/kg) did oxcarbazepine reduce the rotarod performance time. Conclusions: We conclude that oxcarbazepine reduces mechanical and cold allodynia in a rat neuropathic pain model and may be a candidate for the management of neuropathic pain.