Selective cannabinoid CB1 receptor activation inhibits spinal nociceptive transmission in vivo

Cannabinoid(1) (CB1) receptors are located at CNS sites, including the spin al cord, involved in somatosensory processing. Analgesia is one of the tetr ad of behaviors associated with cannabinoid agonists. Here, effects of a po tent cannabinoid CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) on evoked responses of dorsal horn neurons in anesthetized rats were inves tigated. Extracellular recordings of convergent dorsal horn neurons were ma de in halothane anesthetized Sprague-Dawley rats (n=16). Effects of spinal application of ACEA on electrically evoked responses of dorsal horn neurons were studied. Mean maximal effects of 0.5, 5, 50, and 500 ng/50 mul ACEA o n the C-fiber-mediated postdischarge response were 79 +/-6, 62 +/- 10, and 54 +/-7% (P<0.01), 45<plus/minus>6% (P<0.01), of control, respectively. ACE A (500 ng/50 <mu>l) also reduced the C-fiber-evoked nonpotentiated response s of neurons (59 +/-9% of control, P<0.05) and A<delta>-fiber-evoked respon ses of neurons (68 +/- 10% of control, P<0.01). Minor effects of ACEA on A< beta>-fiber-evoked responses were observed. Spinal preadministration of the selective CB1 receptor antagonist SR141716A (0.01 mug/50 mul) significantl y reduced effects of ACEA (500 ng/50 mul) on postdischarge responses of dor sal horn neurons. This study demonstrates that spinal CB1 receptors modulat e the transmission of C- and A delta -fiber-evoked responses in anesthetize d rats; this may reflect pre- and/or postsynaptic effects of cannabinoids o n nociceptive transmission. CB1 receptors inhibit synaptic release of gluta mate in rat dorsolateral striatum, a similar mechanism of action may underl ie the effects of ACEA on noxious evoked responses of spinal neurons report ed here.