CANNABINOID 1 RECEPTOR ACTIVATION INHIBITS TRANSIENT RECEPTOR POTENTIAL VANILLOID TYPE 1 RECEPTOR-MEDIATED CATIONIC INFLUX INTO RAT CULTURED PRIMARY SENSORY NEURONS

The majority of polymodal nociceptors express the non-selective cationic channel, transient receptor potential vanilloid type 1 receptor, which plays a pivotal role in the development of inflammatory heat hyperalgesia and visceral hyper-reflexia. Thus, blocking transient receptor potential vanilloid type I receptor-mediated signalling in primary sensory neurons would provide significant pain relief and reduced visceral hyperactivity in inflammatory conditions. Here, we report that cannabinoids including the endogenous agent, anandamide (3-30 nM) and the synthetic compounds, arachidonyl-2-chloroethylamide (500 nM) and 1,1-dimethylheptyl-11-hydroxytetrahydrocannabinol (1 mu M) significantly reduce cobalt influx that is mediated through the transient receptor potential vanilloid type 1 receptor in rat cultured primary sensory neurons. The cannabinoid-evoked inhibitory effect can be reversed by rimonabant (200 nM), an antagonist of the cannabinoid I receptor. While anandamide- and arachidonyl-2-chloroethylamide fail to evoke inhibitory effects on the transient receptor potential vanilloid type I receptor-mediated responses, the inhibitory effect of 1,1-dimethylheptyl-11-hydroxytetrahydrocannabinol is maintained, when the cannablnoids are applied together with the inflammatory mediators, prostaglandin E-2 (10 mu M) and bradykinin (10 mu M). These results indicate that activation of the cannabinoid 1 receptor can reduce the activity of the transient receptor potential vanilloid type 1 receptor in primary sensory neurons, though the inhibitory effect of agents, which activate both the cannabinoid 1 and the transient receptor potential vanilloid type 1 receptor could be reduced in inflammatory conditions. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.