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Analgesic effects of amiodarone in mouse models of pain

Authors Kotoda M, Ino H, Kumakura Y, Iijima T, Ishiyama T, Matsukawa T

Received 29 November 2018

Accepted for publication 6 May 2019

Published 6 June 2019 Volume 2019:12 Pages 1825—1832

DOI https://doi.org/10.2147/JPR.S196480

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Erica Wegrzyn


Masakazu Kotoda,1 Hirofumi Ino,1 Yasutomo Kumakura,1 Tetsuya Iijima,1 Tadahiko Ishiyama,2 Takashi Matsukawa1

1Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan; 2Surgical Center, University of Yamanashi Hospital, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan

Purpose: Although amiodarone is classified as a Vaughan-Williams class Ⅲ antiarrhythmic drug, it has inhibitory effects on voltage-gated sodium and calcium channels and on β-adrenergic receptors. Given these pharmacological profiles, amiodarone may have analgesic properties. Most patients who are prescribed amiodarone possess multiple cardiovascular risk factors. Despite the fact that pain plays a crucial role as a clinical indicator of cardiovascular events, the effects of amiodarone on pain have not been investigated. The aim of the current study was to investigate the analgesic effects of amiodarone by using mouse models of pain in an effort to elucidate underlying mechanisms.
Methods: Adult male C57B6 mice received single bolus intraperitoneal injections of amiodarone at doses of 25, 50, 100, and 200 mg/kg, while the mice in the control group received only normal saline. The analgesic effects of amiodarone were evaluated using the acetic acid-induced writhing test, formalin test, and tail withdrawal test. In addition, the potassium channel opener NS1643, voltage-gated sodium channel opener veratrine, calcium channel opener BAYK8644, and selective β-adrenergic agonist isoproterenol were used to uncover the underlying mechanism.
Results: During the acetic acid-induced writhing test, formalin test, and tail withdrawal test, amiodarone induced analgesic responses in a dose-dependent manner. The analgesic effects of amiodarone were abolished by veratrine but not by NS1643, BAYK8644, or isoproterenol.
Conclusion: Amiodarone induced analgesic responses in a dose-dependent manner, likely by blocking voltage-gated sodium channels. These results indicate that clinical doses of amiodarone can affect nociception and may mask or attenuate pain induced by acute cardiovascular events.

Keywords: amiodarone, antinociception, pain, sodium channels

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