Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn neurones in a rat model of mononeuropathy

Selective ligation of the L5/L6 spinal nerves produces a partial denervatio n of the hindpaw and has proved to be a useful model for studying the mecha nisms underlying neuropathic pain. Two weeks after surgery, in vivo electro physiological studies were performed in sham operated and nerve injured rat s and the responses of spinal dorsal horn neurones to controlled electrical and natural (mechanical and heat) stimuli were recorded. The systemic effe cts of three N-methyl-D-aspartate receptor (NMDA) antagonists, ketamine (1- 10 mg/kg), memantine (1-20 mg/kg) and MK-801 (0.1-5 mg/kg) were compared. K etamine a clinically available NMDA receptor antagonist, produced greater r eductions of the postdischarge, thermal (10 mg/kg, P = 0.02), and mechanica l evoked responses in spinal nerve ligated (SNL) rats (von Frey 9 g, 1 mg/k g, P = 0.04; 5 mg/kg, P = 0.01; 10 mg/kg, P = 0.05; von Frey 50 g, 5 mg/kg, P = 0.02; 10 mg/kg, P = 0.003). The inhibition of wind-up was comparable i n both animal groups. Memantine produced powerful inhibitions of wind-up af ter nerve injury with little effect in sham controls (5 mg/kg, P = 0.02). T he postdischarge, mechanical and thermal evoked responses were reduced to s imilar extents by memantine in both experimental groups. The effects of MK- 801 were comparable between SNL and sham operated rats for all neuronal mea sures (wind-up, postdischarge, thermal and noxious mechanical evoked respon ses). The differential blocking abilities of these antagonists on the vario us neuronal responses may relate to the characteristics of their voltage-de pendent blockage of the channel associated with the receptor. The favourabl e side effect profile of memantine supports its potential use for the treat ment of neuropathic pain. (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.