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Synapse. 2018 Jul 11; doi: 10.1002/syn.22056. Epub 2018 Jul 11.

Evaluation of the antinociceptive activities of several sodium channel blockers using veratrine test in mice.

Synapse (New York, N.Y.)

Kazumi Yoshizawa, Narumaki Arai, Yukina Suzuki, Toka Nakamura, Kota Takeuchi, Reinii Sakamoto, Ritsuko Masuda

Affiliations

  1. Laboratory of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
  2. Department of Anesthesiology, Tokai University Hachioji Hospital, Tokyo, Japan.

PMID: 29993143 DOI: 10.1002/syn.22056

Abstract

An important role of voltage-gated sodium channels (VGSCs) in many different pain states has been established in animal models and humans wherein sodium channel blockers partially ameliorate pain. However, behavioral tests for screening analgesics that exhibit pharmacologic action by acting on VGSCs are rarely reported, and there are no studies on antinociception using veratrine as a nociceptive agent. The aim of the present study was to examine the amount of nociceptive behavior evoked by subcutaneous administration of veratrine into the hind paw and investigate whether veratrine can be used as a VGSC agonist to test the pharmacological properties of candidate analgesics via sodium channel blockade. We report for the first time that intraplantar injection of veratrine produced a reproducible nociceptive response in mice. Furthermore, several sodium channel blockers, namely carbamazepine, valproate, mexiletine, and the selective Nav1.7 inhibitor PF-04856264, but not flecainide or pilsicainide, reduced veratrine-induced nociception. In contrast, calcium channel blockers gabapentin and ethosuximide did not change veratrine-induced nociception. The veratrine test in mice might be a useful tool, at least in part, to evaluate the potential analgesic effect of sodium channel blockers.

© 2018 Wiley Periodicals, Inc.

Keywords: mouse; nociception; sodium channel blockers; veratrine

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