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 (1nM-30nM) and 1,1-dimethylheptyl-11-hydroxytetrahydrocannabinol (HU210; 1μM-10μM) was assessed on capsaicin (10nM or 100nM)-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 E2 (5 μM) and nerve growth factor (100ng/ml) for 10min. 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.
- Transient receptor potential vanilloid type 1 ion channel
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)