Effects of cannabinoids on capsaicin receptor activity following exposure of primary sensory neurons to inflammatory mediators.

Abstract Aims Activation of the cannabinoid 1 (CB1) receptor in cultured primary sensory neurons reduces responses mediated through the transient receptor potential vanilloid type 1 receptor (TRPV1), which plays a pivotal role in the development of heat hyperalgesia and visceral hyper-reflexia in inflammatory conditions. Here, we studied the effect of cannabinoid-evoked inhibitory effect on TRPV1 in inflammatory conditions. Main methods The effect of anandamide (1 nM–30 nM) and 1,1-dimethylheptyl-11-hydroxytetrahydrocannabinol (HU210; 1 μM–10 μM) was assessed on capsaicin (10 nM or 100 nM)-evoked cobalt uptake in rat cultured primary sensory neurons following the incubation of the cells in an “inflammatory environment” created by the major inflammatory mediators, bradykinin (5 μM), prostaglandin E 2 (5 μM) and nerve growth factor (100 ng/ml) for 10 min. Key findings 1 nM and 10 nM anandamide significantly reduced the 10 nM but not the 100 nM capsaicin-evoked responses. HU210 did not produce a significant change in responses evoked by capsaicin at either of its concentrations. The anandamide-induced inhibitory effect could not be reversed by the CB1 receptor antagonist, rimonabant (200 nM) or the membrane-permeable cAMP analogue, 8Br-cAMP (100 μM). Significance These findings suggest that anandamide may inhibit TRPV1-mediated responses in a non-CB1/non-cannabinoid 2 receptor-dependent manner in primary sensory neurons in inflammatory conditions.