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 nocicept ive responses of wide dynamic range (WDR) neurons in the lumbar spinal cord were investigated in anesthetized rats. WDR neurons were identif ied by their responses to innocuous brushing and to a range of pressur e stimuli from innocuous to noxious. Noxious pressure was applied to r egions of the ipsilateral hind paw corresponding to the receptive fiel d of the neuron. WIN 55,212-2 (125 mu g/kg and 250 mu g/kg, i.v.) prod uced a profound inhibition of firing evoked by the noxious pressure st imulus. By contrast, the cannabinoid did not alter the evoked activity of non-nociceptive neurons in response to non-noxious levels of stimu lation. Treatment with either vehicle or the inactive enantiomer WIN 5 5,212-3 (250 mu g/kg) failed to alter noxious stimulus-evoked activity of WDR neurons. These data provide direct evidence for cannabinoid-me diated inhibition of pain neurotransmission in the spinal dorsal hem. The site of action for these effects remains to be determined.