Dietary Zinc Deficiency Induces Cav3.2-Dependent Nociceptive Hypersensitivity in Mice

Cav3.2 channels belong to the T-type calcium channel (T-channel) family, i.e., low voltage-activated cal- cium channels, and are abundantly expressed in the nociceptors, playing a principal role in the development of pathological pain. The channel activity of Cav3.2 is suppressed by zinc under physiological conditions. We thus tested whether dietary zinc deficiency would cause Cav3.2-dependent nociceptive hypersensitivity in mice. In the mice fed with zinc deficient diet for 2 weeks, plasma zinc levels declined by more than half, and mechanical allodynia developed. The dietary zinc deficiency-induced allodynia was restored by T-channel inhibitors or by Cav3.2 gene silencing. These data demonstrate that zinc deficiency induces Cav3.2-dependent nociceptive hypersensitivity in mice, thereby suggesting that pain experienced by patients with diseases ac- companied by zinc deficiency (e.g., chronic kidney disease) might involve the increased Cav3.2 activity.

Automated summary

Cav3.2 channels, belonging to the T-type calcium channel family, play a crucial role in the development of pathological pain. Zinc deficiency induces Cav3.2-dependent nociceptive hypersensitivity in mice, and this sensitivity can be restored by T-channel inhibitors or silencing the Cav3.2 gene.