Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite

Takahiro Ueno1, Hironori Tsuchiya2, Maki Mizogami1, Ko Takakura11Department of Anesthesiology, Asahi University School of Dentistry, Mizuho, Gifu, Japan; 2Department of Dental Basic Education, Asahi University School of Dentistry, Mizuho, Gifu, JapanAbstract: The presence of inflammation decreases l...

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Autores principales:	Takahiro Ueno, Hironori Tsuchiya, Maki Mizogami, Ko Takakura
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2008
Materias:	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b8ec0de7e8b64276b5f78d362847cf78
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spelling	oai:doaj.org-article:b8ec0de7e8b64276b5f78d362847cf782021-12-02T00:23:12ZLocal anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite1178-7031https://doaj.org/article/b8ec0de7e8b64276b5f78d362847cf782008-11-01T00:00:00Zhttp://www.dovepress.com/local-anesthetic-failure-associated-with-inflammation-verification-of--a2574https://doaj.org/toc/1178-7031Takahiro Ueno1, Hironori Tsuchiya2, Maki Mizogami1, Ko Takakura11Department of Anesthesiology, Asahi University School of Dentistry, Mizuho, Gifu, Japan; 2Department of Dental Basic Education, Asahi University School of Dentistry, Mizuho, Gifu, JapanAbstract: The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. We verified the acidosis mechanism by studying the drug and membrane lipid interaction under acidic conditions together with proposing an alternative hypothesis. Liposomes and nerve cell model membranes consisting of phospholipids and cholesterol were treated at different pH with lidocaine, prilocaine and bupivacaine (0.05%&ndash;0.2%, w/v). Their membrane-interactive potencies were compared by the induced-changes in membrane fluidity. Local anesthetics fluidized phosphatidylcholine membranes with the potency being significantly lower at pH 6.4 than at pH 7.4 (p &lt;&nbsp;0.01), supporting the acidosis theory. However, they greatly fluidized nerve cell model membranes even at pH 6.4 corresponding to inflamed tissues, challenging the conventional mechanism. Local anesthetics acted on phosphatidylserine liposomes, as well as nerve cell model membranes, at pH 6.4 with almost the same potency as that at pH 7.4, but not on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin liposomes. Since the positively charged anesthetic molecules are able to interact with nerve cell membranes by ion-paring with anionic components like phosphatidylserine, tissue acidosis is not essentially responsible for the local anesthetic failure associated with inflammation. The effects of local anesthetics on nerve cell model membranes were inhibited by treating with peroxynitrite (50 &mu;M), suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia.Keywords: inflammatory acidosis, local anesthetic failure, membrane lipid interaction, hypothetic mechanism, inflammatory peroxynitrite Takahiro UenoHironori TsuchiyaMaki MizogamiKo TakakuraDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2008, Iss default, Pp 41-48 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Takahiro Ueno Hironori Tsuchiya Maki Mizogami Ko Takakura Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite
description	Takahiro Ueno1, Hironori Tsuchiya2, Maki Mizogami1, Ko Takakura11Department of Anesthesiology, Asahi University School of Dentistry, Mizuho, Gifu, Japan; 2Department of Dental Basic Education, Asahi University School of Dentistry, Mizuho, Gifu, JapanAbstract: The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. We verified the acidosis mechanism by studying the drug and membrane lipid interaction under acidic conditions together with proposing an alternative hypothesis. Liposomes and nerve cell model membranes consisting of phospholipids and cholesterol were treated at different pH with lidocaine, prilocaine and bupivacaine (0.05%&ndash;0.2%, w/v). Their membrane-interactive potencies were compared by the induced-changes in membrane fluidity. Local anesthetics fluidized phosphatidylcholine membranes with the potency being significantly lower at pH 6.4 than at pH 7.4 (p &lt;&nbsp;0.01), supporting the acidosis theory. However, they greatly fluidized nerve cell model membranes even at pH 6.4 corresponding to inflamed tissues, challenging the conventional mechanism. Local anesthetics acted on phosphatidylserine liposomes, as well as nerve cell model membranes, at pH 6.4 with almost the same potency as that at pH 7.4, but not on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin liposomes. Since the positively charged anesthetic molecules are able to interact with nerve cell membranes by ion-paring with anionic components like phosphatidylserine, tissue acidosis is not essentially responsible for the local anesthetic failure associated with inflammation. The effects of local anesthetics on nerve cell model membranes were inhibited by treating with peroxynitrite (50 &mu;M), suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia.Keywords: inflammatory acidosis, local anesthetic failure, membrane lipid interaction, hypothetic mechanism, inflammatory peroxynitrite
format	article
author	Takahiro Ueno Hironori Tsuchiya Maki Mizogami Ko Takakura
author_facet	Takahiro Ueno Hironori Tsuchiya Maki Mizogami Ko Takakura
author_sort	Takahiro Ueno
title	Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite
title_short	Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite
title_full	Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite
title_fullStr	Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite
title_full_unstemmed	Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite
title_sort	local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite
publisher	Dove Medical Press
publishDate	2008
url	https://doaj.org/article/b8ec0de7e8b64276b5f78d362847cf78
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Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite

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