Cannabinoids attenuate depolarization-dependent CA(2-) influx in intermediate-size primary afferent neurons of adult rats

CBI receptors have been localized to primary afferent neurons. but little is known about the direct effect of cannabinoids on these neurons. The depolarization-evoked increase in the concentration of free intracellular calcium ([Ca2-](i)), measured by rnicrofluorimetry. Was used as a bioassay for the effect of cannabinoids on isolated, adult rat primary afferent neurons 20 28 h after dissociation of dorsal root ganglia, Cannabinoid agonists CP 55,940 (100 nM) and WIN 5,212-2 (1 muM) had no effect on the mean K+-evoked increase in [Ca2+](i) in neurons with a somal area < 800 mum(2). but the ligands attenuated the evoked increase in [Ca2+](i) by 35% in neurons defined as intermediate in size (800-1500 mum(2)). The effects of CP 55,940 and WIN 55.212-2 were mediated by the CB1 receptor on the basis of relative effective e concentrations, blockade by the CB1 receptor antagonist SR141716A and lack of effect of WIN 55.212-3. Intermediate-size neurons rarely responded to capsaicin ( 100 nM). Although cannabinoid agonists generally did not inhibit depolarization-evoked increases in [Ca2+](i) in small neurons, immunocytochemical studies indicated that CB1 receptor-immuno-reactivity occurred in this population. CBI receptor-immunoreactive neurons ranged in size from 227 to 2995 mum2 (mean somal area of 1044 mum(2)). In double labeling studies. CBI receptor-immunoreactivity co-localized kith labeling for calcitonin gene-related peptide and RT97 a marker for myelination. in some primary afferent neurons, The decrease in evoked Ca2+ influx indicates that cannabinoids decrease conductance through voltage-dependent calcium channels in a subpopulation of primary afferent neurons. Modulation of calcium channels is one mechanism by which cannabinoids may decrease transmitter release from primary afferent neurons. An effect on voltage-dependent calcium channels, however. represents, only one possible effect of cannabinoids on primary afferent neurons. Identifying the mechanisms by which cannabinoids modulate nociceptive neurons will increase our understanding of how cannabinoids produce anti-nociception in normal animals and animals with tissue injury. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.