The neurobiology of cannabinoid analgesia

The discovery of cannabinoid receptors and their putative endogenous ligand s raises questions as to the nature of the effects produced by cannabinoids on neural circuits that mediate pain and whether endogenous cannabinoids p roduced by the brain or in the periphery serve naturally to modulate pain. A sizable body of previous work showed that cannabinoid agonists suppress p ain behavior in a variety of models of acute and chronic pain. However, at appropriate doses, cannabinoids also profoundly suppress motor behavior (se e Sanudo-Pena et al., this volume), which complicates the interpretation of behavioral analgesia since a motor response is the endpoint of virtually a ll such studies. Studies conducted in this laboratory used biochemical and neurophysiological measures to determine whether cannabinoids suppress noci ceptive neurotransmission. The results showed that cannabinoids suppress no ciceptive neurotransmission at the level of the spinal cord and the thalamu s. These effects are reversible, receptor mediated, selective for painful a s opposed to nonpainful somatic stimuli, and track the behavioral analgesia both in time course and potency.