Cargando…

Amiodarone Provides Long-Lasting Local Anesthesia and Analgesia in Open-State Mouse Nociceptors

Local anesthetics with long-lasting effects and selectivity for nociceptors have been sought over the past decades. In this study, we investigated whether amiodarone, a multiple channel blocker, provides long-lasting local anesthesia and whether adding a TRPV1 channel activator selectively prolongs...

Descripción completa

Detalles Bibliográficos
Autores principales: Kotoda, Masakazu, Matsuoka, Toru, Wada, Keiichi, Jayakar, Selwyn, Ino, Hirofumi, Kawago, Koji, Kumakura, Yasutomo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971742/
https://www.ncbi.nlm.nih.gov/pubmed/35370742
http://dx.doi.org/10.3389/fphar.2022.872477
_version_ 1784679698909888512
author Kotoda, Masakazu
Matsuoka, Toru
Wada, Keiichi
Jayakar, Selwyn
Ino, Hirofumi
Kawago, Koji
Kumakura, Yasutomo
author_facet Kotoda, Masakazu
Matsuoka, Toru
Wada, Keiichi
Jayakar, Selwyn
Ino, Hirofumi
Kawago, Koji
Kumakura, Yasutomo
author_sort Kotoda, Masakazu
collection PubMed
description Local anesthetics with long-lasting effects and selectivity for nociceptors have been sought over the past decades. In this study, we investigated whether amiodarone, a multiple channel blocker, provides long-lasting local anesthesia and whether adding a TRPV1 channel activator selectively prolongs sensory anesthetic effects without prolonging motor blockade. Additionally, we examined whether amiodarone provides long-lasting analgesic effects against inflammatory pain without TRPV1 channel activator co-administration. In the sciatic nerve block model, 32 adult C57BL/6J mice received either bupivacaine, amiodarone with or without capsaicin (a TRPV1 agonist), or vehicle via peri-sciatic nerve injection. Sensory and motor blockade were assessed either by pinprick and toe spread tests, respectively. In another set of 16 mice, inflammatory pain was induced in the hind paw by zymosan injection, followed by administration of either amiodarone or vehicle. Mechanical and thermal sensitivity and paw thickness were assessed using the von Frey and Hargreaves tests, respectively. The possible cardiovascular and neurological side effects of local amiodarone injection were assessed in another set of 12 mice. In the sciatic nerve block model, amiodarone produced robust anesthesia, and the co-administration of TRPV1 agonist capsaicin prolonged the duration of sensory blockade, but not that of motor blockade [complete sensory block duration: 195.0 ± 9.8 min vs. 28.8 ± 1.3 min, F (2, 21) = 317.6, p < 0.01, complete motor block duration: 27.5 ± 1.6 min vs. 21.3 ± 2.3 min, F (2, 22) = 11.1, p = 0.0695]. In the zymosan-induced inflammatory pain model, low-dose amiodarone was effective in reversing the mechanical and thermal hypersensitivity not requiring capsaicin co-administration [50% withdrawal threshold at 8 h (g): 0.85 ± 0.09 vs. 0.25 ± 0.08, p < 0.01, withdrawal latency at 4 h (s) 8.5 ± 0.5 vs. 5.7 ± 1.4, p < 0.05]. Low-dose amiodarone did not affect zymosan-induced paw inflammation. Local amiodarone did not cause cardiovascular or central nervous system side effects. Amiodarone may have the potential to be a long-acting and nociceptor-selective local anesthetic and analgesic method acting over open-state large-pore channels.
format Online
Article
Text
id pubmed-8971742
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89717422022-04-02 Amiodarone Provides Long-Lasting Local Anesthesia and Analgesia in Open-State Mouse Nociceptors Kotoda, Masakazu Matsuoka, Toru Wada, Keiichi Jayakar, Selwyn Ino, Hirofumi Kawago, Koji Kumakura, Yasutomo Front Pharmacol Pharmacology Local anesthetics with long-lasting effects and selectivity for nociceptors have been sought over the past decades. In this study, we investigated whether amiodarone, a multiple channel blocker, provides long-lasting local anesthesia and whether adding a TRPV1 channel activator selectively prolongs sensory anesthetic effects without prolonging motor blockade. Additionally, we examined whether amiodarone provides long-lasting analgesic effects against inflammatory pain without TRPV1 channel activator co-administration. In the sciatic nerve block model, 32 adult C57BL/6J mice received either bupivacaine, amiodarone with or without capsaicin (a TRPV1 agonist), or vehicle via peri-sciatic nerve injection. Sensory and motor blockade were assessed either by pinprick and toe spread tests, respectively. In another set of 16 mice, inflammatory pain was induced in the hind paw by zymosan injection, followed by administration of either amiodarone or vehicle. Mechanical and thermal sensitivity and paw thickness were assessed using the von Frey and Hargreaves tests, respectively. The possible cardiovascular and neurological side effects of local amiodarone injection were assessed in another set of 12 mice. In the sciatic nerve block model, amiodarone produced robust anesthesia, and the co-administration of TRPV1 agonist capsaicin prolonged the duration of sensory blockade, but not that of motor blockade [complete sensory block duration: 195.0 ± 9.8 min vs. 28.8 ± 1.3 min, F (2, 21) = 317.6, p < 0.01, complete motor block duration: 27.5 ± 1.6 min vs. 21.3 ± 2.3 min, F (2, 22) = 11.1, p = 0.0695]. In the zymosan-induced inflammatory pain model, low-dose amiodarone was effective in reversing the mechanical and thermal hypersensitivity not requiring capsaicin co-administration [50% withdrawal threshold at 8 h (g): 0.85 ± 0.09 vs. 0.25 ± 0.08, p < 0.01, withdrawal latency at 4 h (s) 8.5 ± 0.5 vs. 5.7 ± 1.4, p < 0.05]. Low-dose amiodarone did not affect zymosan-induced paw inflammation. Local amiodarone did not cause cardiovascular or central nervous system side effects. Amiodarone may have the potential to be a long-acting and nociceptor-selective local anesthetic and analgesic method acting over open-state large-pore channels. Frontiers Media S.A. 2022-03-18 /pmc/articles/PMC8971742/ /pubmed/35370742 http://dx.doi.org/10.3389/fphar.2022.872477 Text en Copyright © 2022 Kotoda, Matsuoka, Wada, Jayakar, Ino, Kawago and Kumakura. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Kotoda, Masakazu
Matsuoka, Toru
Wada, Keiichi
Jayakar, Selwyn
Ino, Hirofumi
Kawago, Koji
Kumakura, Yasutomo
Amiodarone Provides Long-Lasting Local Anesthesia and Analgesia in Open-State Mouse Nociceptors
title Amiodarone Provides Long-Lasting Local Anesthesia and Analgesia in Open-State Mouse Nociceptors
title_full Amiodarone Provides Long-Lasting Local Anesthesia and Analgesia in Open-State Mouse Nociceptors
title_fullStr Amiodarone Provides Long-Lasting Local Anesthesia and Analgesia in Open-State Mouse Nociceptors
title_full_unstemmed Amiodarone Provides Long-Lasting Local Anesthesia and Analgesia in Open-State Mouse Nociceptors
title_short Amiodarone Provides Long-Lasting Local Anesthesia and Analgesia in Open-State Mouse Nociceptors
title_sort amiodarone provides long-lasting local anesthesia and analgesia in open-state mouse nociceptors
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971742/
https://www.ncbi.nlm.nih.gov/pubmed/35370742
http://dx.doi.org/10.3389/fphar.2022.872477
work_keys_str_mv AT kotodamasakazu amiodaroneprovideslonglastinglocalanesthesiaandanalgesiainopenstatemousenociceptors
AT matsuokatoru amiodaroneprovideslonglastinglocalanesthesiaandanalgesiainopenstatemousenociceptors
AT wadakeiichi amiodaroneprovideslonglastinglocalanesthesiaandanalgesiainopenstatemousenociceptors
AT jayakarselwyn amiodaroneprovideslonglastinglocalanesthesiaandanalgesiainopenstatemousenociceptors
AT inohirofumi amiodaroneprovideslonglastinglocalanesthesiaandanalgesiainopenstatemousenociceptors
AT kawagokoji amiodaroneprovideslonglastinglocalanesthesiaandanalgesiainopenstatemousenociceptors
AT kumakurayasutomo amiodaroneprovideslonglastinglocalanesthesiaandanalgesiainopenstatemousenociceptors