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

DOI http://dx.doi.org/10.2147/JIR.S3982

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 https://www.dovepress.com/terms.php 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:

Synthesis and anti-fungal effect of silver nanoparticles–chitosan composite particles

Wang LS, Wang CY, Yang CH, Hsieh CL, Chen SY, Shen CY, Wang JJ, Huang KS

International Journal of Nanomedicine 2015, 10:2685-2696

Published Date: 1 April 2015

Scleral buckling procedure with chandelier illumination for pediatric rhegmatogenous retinal detachment

Yokoyama T, Kanbayashi K, Yamaguchi T

Clinical Ophthalmology 2015, 9:169-173

Published Date: 23 January 2015

Differential effects of dosing regimen on the safety and efficacy of dasatinib: retrospective exposure–response analysis of a Phase III study

Wang X, Roy A, Hochhaus A, Kantarjian HM, Chen TT, Shah NP

Clinical Pharmacology: Advances and Applications 2013, 5:85-97

Published Date: 10 June 2013

Lactose intolerance: diagnosis, genetic, and clinical factors

Mattar R, Mazo DF, Carrilho FJ

Clinical and Experimental Gastroenterology 2012, 5:113-121

Published Date: 5 July 2012

Integrative systems of genomic risk markers for cancer and other diseases: future of predictive medicine

Yuzhalin AE, Kutikhin AG

Cancer Management and Research 2012, 4:131-135

Published Date: 23 May 2012

Filament formation associated with spirochetal infection: a comparative approach to Morgellons disease

Middelveen MJ, Stricker RB

Clinical, Cosmetic and Investigational Dermatology 2011, 4:167-177

Published Date: 14 November 2011

Neurotransmitter testing of the urine: a comprehensive analysis

Marty Hinz, Alvin Stein, George Trachte, et al

Research and Reports in Urology 2010, 2:177-183

Published Date: 7 October 2010

Prevalence and risk factors of microalbuminuria in Thai nondiabetic hypertensive patients

Pongsathorn Gojaseni, Angkana Phaopha, Worawon Chailimpamontree, et al

Vascular Health and Risk Management 2010, 6:157-165

Published Date: 11 March 2010

Risk factors associated with methamphetamine use and heart failure among Native Hawaiians and other Pacific Island peoples

Marjorie K Mau, Karynna Asao, Jimmy Efird, Erin Saito, Robert Ratner, et al

Vascular Health and Risk Management 2009, 5:45-52

Published Date: 7 December 2008