Inhibition of noxious stimulus-evoked activity of spinal cord dorsal horn neurons by the cannabinoid WIN 55,212-2.

The effects of a potent synthetic cannabinoid WIN 55,212-2 on nociceptive responses of wide dynamic range (WDR) neurons in the lumbar spinal cord were investigated in anesthetized rats. WDR neurons were identified by their responses to innocuous brushing and to a range of pressure stimuli from innocuous to noxious. Noxious pressure was applied to regions of the ipsilateral hind paw corresponding to the receptive field of the neuron. WIN 55,212-2 (125 micrograms/kg and 250 micrograms/kg, i.v.) produced a profound inhibition of firing evoked by the noxious pressure stimulus. By contrast, the cannabinoid did not alter the evoked activity of non-nociceptive neurons in response to non-noxious levels of stimulation. Treatment with either vehicle or the inactive enantiomer WIN 55,212-3 (250 micrograms/kg) failed to alter noxious stimulus-evoked activity of WDR neurons. These data provide direct evidence for cannabinoid-mediated inhibition of pain neurotransmission in the spinal dorsal horn. The site of action for these effects remains to be determined.