Selective
ligation of the L5/L6 spinal nerves produces a partial
denervation of the hindpaw and has proved to be a useful model for studying the mechanisms underlying
neuropathic pain. Two weeks after surgery, in vivo electrophysiological studies were performed in
sham operated and nerve injured rats and the responses of spinal dorsal horn neurones to controlled electrical and natural (mechanical and heat) stimuli were recorded. The systemic effects 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.
Ketamine a clinically available
NMDA receptor antagonist, produced greater reductions of the postdischarge, thermal (10 mg/kg, P=0.02), and mechanical evoked responses in spinal nerve ligated (SNL) rats (von Frey 9 g, 1 mg/kg, 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 in both animal groups.
Memantine produced powerful inhibitions of wind-up after nerve injury with little effect in
sham controls (5 mg/kg, P=0.02). The postdischarge, mechanical and thermal evoked responses were reduced to similar extents by
memantine in both experimental groups. The effects of
MK-801 were comparable between SNL and
sham operated rats for all neuronal measures (wind-up, postdischarge, thermal and noxious mechanical evoked responses). The differential blocking abilities of these antagonists on the various neuronal responses may relate to the characteristics of their voltage-dependent blockage of the channel associated with the receptor. The favourable side effect profile of
memantine supports its potential use for the treatment of
neuropathic pain.