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

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 microM-10 microM) 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 microM), prostaglandin E(2) (5 microM) 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 microM).

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.