Cannabinoid receptors undergo axonal flow in sensory nerves

Cannabinoids modulate nociceptive processing through central and peripheral mechanisms. The present study was conducted to evaluate axonal flow of can nabinoid receptors from the dorsal root ganglion to the periphery and to id entify the putative involvement of CB1 and/or CB2 receptor subtypes. The sc iatic nerve was tightly ligated to dam the how of cannabinoid receptors to the periphery. The densities of cannabinoid receptors proximal and distal t o one or two tightly constrictive ligatures was evaluated using in vitro re ceptor binding and high-resolution emulsion autoradiography, In both models , [H-3]CP55,940 binding accumulated proximal as opposed to distal to the li gature. These data indicate that axonal transport of cannabinoid receptors to the periphery was occluded by tight constriction of the sciatic nerve, I n situ hybridization histochemistry revealed that dorsal root ganglia cells synthesize CB1 but not CB2 receptor messenger RNA. By contrast, CB2 messen ger RNA was highly expressed in sections of rat spleen that were processed together with the dorsal root ganglia, as previously described. These data demonstrate that neuronal cannabinoid CB1 receptors are synthesized in cell s of the dorsal root ganglia and inserted on terminals in the periphery. (C ) 1999 IBRO, Published by Elsevier Science Ltd.