Analgesia by intrathecal delta-9-tetrahydrocannabinol is dependent on Cav3.2 calcium channels

Molecular Brain

Micro Report

Vinicius de Maria Gadotti¹  Gerald W. Zamponi¹  Flavia Tasmin Techera Antunes¹ 

[1] Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada;Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada;Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada;Cumming School of Medicine, University of Calgary, Calgary, AB, Canada;

关键词: Δ-THC;    Cannabinoid receptors;    Cav3.2 channel;    Analgesia;    Pain;   

DOI  :  10.1186/s13041-023-01036-8

 received in 2023-04-26, accepted in 2023-05-17,  发布年份 2023

来源: Springer

【 摘 要 】

Delta-9-tetrahydrocannabinol (Δ9-THC) is known to produce systemic analgesia that involves CB1 and CB2 cannabinoid receptors. However, there is compelling evidence that Δ9-THC can potently inhibit Cav3.2T-type calcium channels which are highly expressed in dorsal root ganglion neurons and in the dorsal horn of the spinal cord. Here, we investigated whether spinal analgesia produced by Δ9-THC involves Cav3.2 channels vis a vis cannabinoid receptors. We show that spinally delivered Δ9-THC produced dose-dependent and long-lasting mechanical anti-hyperalgesia in neuropathic mice, and showed potent analgesic effects in models of inflammatory pain induced by formalin or Complete Freund’s Adjuvant (CFA) injection into the hind paw, with the latter showing no overt sex differences. The Δ9-THC mediated reversal of thermal hyperalgesia in the CFA model was abolished in Cav3.2 null mice, but was unaltered in CB1 and CB2 null animals. Hence, the analgesic effects of spinally delivered Δ9-THC are due to an action on T-type calcium channels, rather than activation of spinal cannabinoid receptors.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 2

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