Cannabinoid modulation of wide dynamic range neurons in the lumbar dorsal horn of the rat by spinally administered WIN55,212-2

The effects of spinally administered cannabinoids on nociceptive responses of wide dynamic range (WDR) neurons in the lumbar spinal cord were investig ated in urethane-anesthetized rats. Noxious thermal stimulation was applied with a Peltier device to regions of the ipsilateral hindpaw corresponding to the receptive fields of isolated neurons. WIN55,212-2 (100 mu g, i.t.), applied topically on the dorsal spinal surface, suppressed noxious heat-evo ked activity in spinal WDR neurons. By contrast, responsiveness was unchang ed following administration of either vehicle or WIN55,212-3, the receptor- inactive enantiomer. WIN55,212-2, administered intrathecally to separate ra ts, produced antinociceptive effects in the tail-flick test with a time cou rse and efficacy that paralleled the suppression of noxious hat-evoked acti vity. These results suggest that cannabinoid modulation of spinal nocicepti ve processing involves direct actions in the spinal dorsal horn and is rela ted to the antinociceptive effects of intrathecally administered cannabinoi ds. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.