Peripheral cannabinoid CB1 receptors inhibit evoked responses of nociceptive neurones in vivo

We investigated the effect of peripheral administration of a selective cannabinoid CB1 receptor agonist arachidonyl-2-choroethylamide (ACEA), on evoked responses of primary afferents in vivo. Extracellular recordings were made from filaments of the saphenous nerve that responded to noxious mechanical stimulation of their receptive fields and effects of ACEA (30 and 50 microg/100 microl, i.a.) were studied. ACEA significantly inhibited evoked responses, effects that were blocked by co-administration of the cannabinoid CB1 receptor antagonist AM251 (30 microg/100 microl). These results demonstrate a cannabinoid CB1 receptor-mediated inhibition of primary afferent nociceptor excitability and provide further support for a peripheral site of action of cannabinoids.