Actions of cannabinoid receptor ligands on rat cultured sensory neurones: implications for antinociception

Cannabinoids modulate nociceptive processing in models of acute, inflammato ry and neuropathic pain. We have investigated the location and function of cannabinoid receptors on cultured neonatal dorsal root ganglion (DRG) neuro nes and F-11 cells, a dorsal root ganglionxneuroblastoma hybridoma which di splays several of the features of authentic DRG neurones. CB1 receptor immu nolabelling was observed on the cell bodies and as fine puncta on processes of both cultured DRG neurones and F-11 cells. Additionally, fluorescence-a ctivated cell sorting (FACS) analysis provided evidence that both CB1 and C B2 receptors are expressed on populations of cells within the cultured DRG and F-11 cells. The cannabinoid receptor agonist (+)-WIN55212 (10 and 100 n M) inhibited the mean voltage-activated Ca2+ current in DRG neurones by 21% and 30%, respectively. The isomer, (-)-WIN55212 (10 and 100 nM) produced s ignificantly less inhibition of 6% and 10% respectively. The CB1 selective receptor antagonist SR141716A (100 nM) enhanced the peak high voltage-activ ated Ca2+ current by 24% and simultaneous application of SR141716A (100 nM) and (+)-WIN55212 (100 nM) resulted in a significant attenuation of the inh ibition obtained with (+)-WIN55212 alone. These data give functional eviden ce for the hypothesis that the analgesic actions of cannabinoids may be med iated by presynaptic inhibition of transmitter release in sensory neurones. (C) 2000 Elsevier Science Ltd. All rights reserved.