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T-type calcium channels, cannabinoids and their roles in pain

Erika K. Harding, Vinicius M. Gadotti, Ivana A. Souza, Maria A. Gandini, Sun Huang, Flavia T.T. Antunes, and Gerald W Zamponi

Cav3.2 T-type calcium channels are known to be important pharmacological targets in chronic pain states. Chronic pain can also be treated with various cannabinoids and terpenes, and previous evidence from the Connor and Lory laboratories suggested that both phyto-cannabinoids and endocannabinoids mediate analgesic effects via actions on T-type channels. Electrophysiological studies indicate that cannabinoid receptors do not functionally modulate Cav3.2 channels, but instead inhibit the activity of Cav2.2 channels by a membrane delimited pathway. By contrast, several terpenes, CBD and THC directly block Cav3.2 channels, and mediate analgesia via actions on this channel subtype when delivered spinally. By contrast THC does not appear to mediate spinal analgesic actions via cannabinoid receptors. Our data support a key role of Cav3.2 channels in the pain relieving activities of cannabis constituents