Recent interest has focused on the potential of
cannabinoids as novel
analgesics. The aim of the present study was to investigate the effect of a potent
cannabinoid agonist,
HU210, on somatosensory transmission in a model of
neuropathic pain. Here, the effects of spinal versus systemic administration of
HU210 on noxious and innocuous evoked responses of spinal neurones of nerve injured (selective
ligation of spinal nerves L5-L6) and
sham operated rats were compared 14-17 days post-surgical intervention. Spinal administration of
HU210 (0.5-500 ng/50 microl) significantly reduced the C-fibre mediated post-discharge response of spinal neurones in
sham operated, but not nerve injured rats. By contrast, spinal
HU210 significantly reduced Adelta-fibre evoked responses of spinal neurones in both
sham operated and nerve injured rats.Systemic administration of
HU210 (6-60 microg/kg) significantly reduced C- and Adelta-fibre evoked responses of spinal neurones in
sham operated rats.
HU210 (60 microg/kg) inhibited the overall C-fibre evoked response (54+/-8% of control, p<0.01), post-discharge response (28+/-12% of control, p<0.01), and Adelta-fibre evoked (48+/-5% of control p<0.01) responses of spinal neurones. In nerve injured rats, systemic administration of
HU210 did not significantly reduce C- or Abeta-fibre evoked responses of spinal neurones. This study demonstrates plasticity of the spinal
cannabinoid receptor system following
peripheral nerve injury.