Cav3.2-dependent hyperalgesia/allodynia following intrathecal and intraplantar zinc chelator administration in rodents

Shiori Tomita; Fumiko Sekiguchi; Katsuki Naoe; Shiyu Shikimi; Yoshihito Kasanami; Maya Ohigashi; Maho Tsubota; Atsufumi Kawabata

doi:10.1016/j.jphs.2023.03.007

Ca_v3.2-dependent hyperalgesia/allodynia following intrathecal and intraplantar zinc chelator administration in rodents

J Pharmacol Sci. 2023 Jun;152(2):86-89. doi: 10.1016/j.jphs.2023.03.007. Epub 2023 Apr 5.

Authors

Shiori Tomita¹, Fumiko Sekiguchi¹, Katsuki Naoe¹, Shiyu Shikimi¹, Yoshihito Kasanami¹, Maya Ohigashi¹, Maho Tsubota¹, Atsufumi Kawabata²

Affiliations

¹ Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, 577-8502, Japan.
² Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, 577-8502, Japan. Electronic address: kawabata@phar.kindai.ac.jp.

PMID: 37169483
DOI: 10.1016/j.jphs.2023.03.007

Abstract

Ca_v3.2, a T-type calcium channel (T-channel) family member, is expressed in the nociceptors and spinal cord, and its activity is largely suppressed by zinc under physiological conditions. In rats, intrathecal and intraplantar administration of a zinc chelator, TPEN, caused T-channel-dependent mechanical hyperalgesia, and the intraplantar, but not intrathecal, TPEN induced Ca_v3.2 upregulation in the dorsal root ganglion. In mice, intraplantar TPEN also caused mechanical allodynia, which was abolished by T-channel inhibitors or Ca_v3.2 gene deletion. Together, spinal and peripheral zinc deficiency appears to enhance Ca_v3.2 activity in the spinal postsynaptic neurons and nociceptors, respectively, thereby promoting pain.

Keywords: Ca(v)3.2 T-type calcium channel; Hyperalgesia; Pain; TPEN; Zinc deficiency.

MeSH terms

Animals
Calcium Channels, T-Type* / genetics
Chelating Agents
Ganglia, Spinal
Hyperalgesia* / chemically induced
Mice
Rats
Rodentia
Zinc

Substances

Chelating Agents
Zinc
N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
Calcium Channels, T-Type