Back to Browse Journals » Journal of Inflammation Research » Volume 1

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

Authors Takahiro Ueno, Hironori Tsuchiya, Maki Mizogami, Ko Takakura

Published 13 November 2008 Volume 2008:1 Pages 41—48


Review by Single-blind

Peer reviewer comments 3

Takahiro Ueno1, Hironori Tsuchiya2, Maki Mizogami1, Ko Takakura1

1Department of Anesthesiology, Asahi University School of Dentistry, Mizuho, Gifu, Japan; 2Department of Dental Basic Education, Asahi University School of Dentistry, Mizuho, Gifu, Japan

Abstract: 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%–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 < 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 μM), suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia.

Keywords: inflammatory acidosis, local anesthetic failure, membrane lipid interaction, hypothetic mechanism, inflammatory peroxynitrite

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF] 


Other articles by this author:

Readers of this article also read:

Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles

Rangger C, Helbok A, von Guggenberg E, Sosabowski J, Radolf T, Prassl R, Andreae F, Thurner GC, Haubner R, Decristoforo C

International Journal of Nanomedicine 2012, 7:5889-5900

Published Date: 27 November 2012

Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles

Wang W, Zhu R, Xie Q, Li A, Xiao Y, Liu H, Cui D, Chen Y, Wang S

International Journal of Nanomedicine 2012, 7:3667-3677

Published Date: 17 July 2012

Nimodipine-loaded mixed micelles: formulation, compatibility, pharmacokinetics, and vascular irritability study

Song X, Jiang Y, Ren CJ, Sun X, Zhang Q, Gong T, Zhang ZR

International Journal of Nanomedicine 2012, 7:3689-3699

Published Date: 13 July 2012

In vitro cellular uptake of evodiamine and rutaecarpine using a microemulsion

Zhang YT, Huang ZB, Zhang SJ, Zhao JH, Wang Z, Liu Y, Feng NP

International Journal of Nanomedicine 2012, 7:2465-2472

Published Date: 18 May 2012

Ultrasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic resonance imaging probes

Frascione D, Diwoky C, Almer G, Opriessnig P, Vonach C, Gradauer K, Leitinger G, Mangge H, Stollberger R, Prassl R

International Journal of Nanomedicine 2012, 7:2349-2359

Published Date: 9 May 2012

Luminescent single-walled carbon nanotube-sensitized europium nanoprobes for cellular imaging

Avti PK, Sitharaman B

International Journal of Nanomedicine 2012, 7:1953-1964

Published Date: 17 April 2012

Toxicity and antibacterial assessment of chitosan-coated silver nanoparticles on human pathogens and macrophage cells

Jena P, Mohanty S, Mallick R, Jacob B, Sonawane A

International Journal of Nanomedicine 2012, 7:1805-1818

Published Date: 3 April 2012

Co-encapsulation of magnetic Fe3O4 nanoparticles and doxorubicin into biodegradable PLGA nanocarriers for intratumoral drug delivery

Jia Y, Yuan M, Yuan H, Huang X, Sui X, Cui X, Tang F, Peng J, Chen J, Lu S, Xu W, Zhang L, Guo Q

International Journal of Nanomedicine 2012, 7:1697-1708

Published Date: 28 March 2012

Delivery of a transforming growth factor β-1 plasmid to mesenchymal stem cells via cationized Pleurotus eryngii polysaccharide nanoparticles

Deng WW, Cao X, Wang M, Qu R, Su WY, Yang Y, Wei YW, Xu XM, Yu JN

International Journal of Nanomedicine 2012, 7:1297-1311

Published Date: 14 March 2012