The Effects of Combination of Verapamil and MK-801 on Rat Neuropathic Pain Model

Abstract

N-methly-D-aspartae receptor is activated by calcium. The effects of a calcium antagonist verapamil and N-methly-D-aspartae receptor antagonist MK-801 on thermal nociception in rat model of chronic nerve injury was well known. We aimed to study the analgesic effects of combination of two drugs using the same model. The present study was constituted on 30 male Sprague Dawley rat weighing 180-220 g. The right common sciatic nerve was exposed and ligated loosely with 4/0 chromic gut under anaesthesia with a barbiturate. The administration of drugs were started after the operation and continued through five days. According to the treatment protocol, verapamil 10 mg kg -1 was administered for four days and on the fifth day MK-801 1 mg kg -1 was combined. The drugs were given with 20 minutes' intervals through intraperitoneal route. Nociceptive tests were performed by Hot Plate Test at 46.5°C throughout a 120 minutes' period at every 30 minutes. The time of withdrawal of the operated limb was accepted as reaction time. Chronic administration of verapamil or MK-801 administration as a sole drug was substantially reduced nociception on neuropathic pain model. The antinociceptive effects of the combination of drugs was found to be lower than values obtained from each drug individually. Pretreatment with a calcium antagonist reduced the sensitivity to N-methyl-D-aspartate receptor on neuropthic pain model. It was concluded that, the binding sites of calcium antagonists and MK-801 on N-methyl-D-aspartate receptors can be close to each other, therefore antagonism may be seen by reducing receptor sensitivity or a reaction during binding.