Functional changes in the inhibitory effect of spinal cannabinoid (CB) receptor activation in nerve injured rats

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.