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Effects of Lidocaine and Articaine on Neuronal Survival and Recovery
Farraj AlbalawiBDS,
Jason C. LimBS,
Kyle V. DiRenzo,
Elliot V. HershDMD, MS, PhD, and
Claire H. MitchellPhD
Article Category: Research Article
Volume/Issue: Volume 65: Issue 2
Online Publication Date: Jan 01, 2018
DOI: 10.2344/anpr-65-02-02
Page Range: 82 – 88

frequently than the inferior alveolar nerve. 4 , 9 Available data indicate that 85–94% of such cases resolve spontaneously within 8 weeks; however, about two-thirds of those that do not recover quickly may never fully recover. 10 This study asked whether in vitro applied articaine was more neurotoxic than lidocaine at levels used clinically and whether the channel block was more sustained with articaine than lidocaine. In contrast to our predictions, we found lidocaine both more toxic and with a greater residual block to cellular responsiveness

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Figure 1. ; Effects of lidocaine and articaine on viability of SH-SY5Y cells. (A) Expression of Na(V) in SH-SY5Y cells. Polymerase chain reaction gel showing cells expressed mRNA for both Na(V)1.2 and Na(V)1.7. Gels show bands of expected size from 3 cell preparations. “-1.2” and “-1.7” indicate lanes where reverse transcriptase was omitted from the mix for Na(V)1.2 and Na(V)1.7, respectively. Bars are 100 base pairs. (B) Example of images of SH-SY5Y cells loaded with the Live/Dead assay in response to various conditions. Cells treated for 5 minutes with 4% articaine or 2% lidocaine (both from the cartridge), washed, then loaded with the Live/Dead dye. Positive control of cells treated with 70% ethanol are shown on the top left, while untreated cells are shown on the right. Green, calcein indicating healthy cells; red, ethidium homodimer indicating compromised cells. Bar = 100 μM. (C) Quantification of Live/Dead levels from SH-SY5Y cells treated with lidocaine + 1 : 100,000 epinephrine or articaine + 1 : 100000 epinephrine from the cartridges used clinically. The reduced viability observed using lidocaine at full strength was not significant (Kruskal-Wallis 1-way analysis on ranks with Dunn's post hoc test). Articaine did not lead to cell death at any strength. Numbers along the abscissa axis indicate the percentage of drug, with 2% lidocaine and 4% articaine the full strength from the cartridge. Numbers along the ordinate represent the ratio of light excited at 488 nm versus 544 nm, normalized to the mean control for each set. *p < .001 methanol versus saline; n = 10. (D) Quantification of the Live/Dead levels from SH-SY5Y cells treated with pure lidocaine or articaine. Lidocaine increased the number of dead cells when used in pure powdered form at the highest concentration, while pure articaine did not alter cell survival. Numbers along the abscissa indicate the concentration in mM, with the highest levels of both drugs equal to the maximum level with the cartridge. Numbers along the ordinate represent the Live/Dead ratio normalized as in C. *p < .001 (methanol and 74 mM lidocaine), n = 18.
Farraj Albalawi,
Jason C. Lim,
Kyle V. DiRenzo,
Elliot V. Hersh, and
Claire H. Mitchell
<bold>Figure 1.</bold>
Figure 1.

Effects of lidocaine and articaine on viability of SH-SY5Y cells. (A) Expression of Na(V) in SH-SY5Y cells. Polymerase chain reaction gel showing cells expressed mRNA for both Na(V)1.2 and Na(V)1.7. Gels show bands of expected size from 3 cell preparations. “-1.2” and “-1.7” indicate lanes where reverse transcriptase was omitted from the mix for Na(V)1.2 and Na(V)1.7, respectively. Bars are 100 base pairs. (B) Example of images of SH-SY5Y cells loaded with the Live/Dead assay in response to various conditions. Cells treated for 5 minutes with 4% articaine or 2% lidocaine (both from the cartridge), washed, then loaded with the Live/Dead dye. Positive control of cells treated with 70% ethanol are shown on the top left, while untreated cells are shown on the right. Green, calcein indicating healthy cells; red, ethidium homodimer indicating compromised cells. Bar = 100 μM. (C) Quantification of Live/Dead levels from SH-SY5Y cells treated with lidocaine + 1 : 100,000 epinephrine or articaine + 1 : 100000 epinephrine from the cartridges used clinically. The reduced viability observed using lidocaine at full strength was not significant (Kruskal-Wallis 1-way analysis on ranks with Dunn's post hoc test). Articaine did not lead to cell death at any strength. Numbers along the abscissa axis indicate the percentage of drug, with 2% lidocaine and 4% articaine the full strength from the cartridge. Numbers along the ordinate represent the ratio of light excited at 488 nm versus 544 nm, normalized to the mean control for each set. *p < .001 methanol versus saline; n = 10. (D) Quantification of the Live/Dead levels from SH-SY5Y cells treated with pure lidocaine or articaine. Lidocaine increased the number of dead cells when used in pure powdered form at the highest concentration, while pure articaine did not alter cell survival. Numbers along the abscissa indicate the concentration in mM, with the highest levels of both drugs equal to the maximum level with the cartridge. Numbers along the ordinate represent the Live/Dead ratio normalized as in C. *p < .001 (methanol and 74 mM lidocaine), n = 18.


Farraj Albalawi,
Jason C. Lim,
Kyle V. DiRenzo,
Elliot V. Hersh, and
Claire H. Mitchell
<bold>Figure 2.</bold>
Figure 2.

Neuronal responsiveness impaired by previous lidocaine treatment. (A) Typical baseline cytoplasmic Ca2+ levels in SH-SY5Y cells. (B) Mean levels of Ca2+ under baseline conditions (B, 5 mM K+) and after exposure to 50 mM K+ (HK) in cells exposed to 2% lidocaine, 4% articaine or control solution 30 minutes before measurements were made. Baseline Ca2+ levels show no significant difference between the 3 treatment groups. While depolarization with the high K+ solution significantly raised cellular Ca2+ levels in the control cells (*p =0.004) and those previously exposed to articaine (**p = .031), the response in cells previously exposed to 2% lidocaine was not significant, Student's t test, n = 15.


Daniel E. BeckerDDS
Article Category: Other
Volume/Issue: Volume 61: Issue 1
Online Publication Date: Jan 01, 2014
Page Range: 26 – 34

in proper doses and concentrations, but they are certainly capable of producing both local and systemic toxicity. Ischemic necrosis of tissues may follow injections of local anesthetics. This can be due to the irritating nature of a solution, pressure from large volumes, or constriction of the vasculature by vasopressors. This concern is greatest when injecting into attached mucosa such as the hard palate. There is also mounting concern regarding direct neurotoxicity related to formulations containing high concentrations, such as 4% articaine and prilocaine

Daniel E BeckerDDS and
Kenneth L ReedDMD
Article Category: Research Article
Volume/Issue: Volume 59: Issue 2
Online Publication Date: Jan 01, 2012
Page Range: 90 – 102

palate. There is also mounting concern regarding direct neurotoxicity related to formulations containing high concentrations such as 4% articaine and prilocaine. Haas and Lennon reported an increased incidence of paresthesias in Canada following the introduction of articaine in the mid-1980s. 14 In 1993 alone, 14 cases of paresthesia were reported, and all were attributed to articaine or prilocaine. When articaine was first submitted for approval to the Food and Drug Administration in the United States, it was identified as having a higher risk for

Steven GanzbergDMD, MS
Article Category: Editorial
Volume/Issue: Volume 62: Issue 4
Online Publication Date: Jan 01, 2015
Page Range: 133 – 134

possible neurotoxicity of sedative and anesthetic agents in very young children. Issues of sometimes subtle behavioral or learning issues have been found in some studies but not others. Animal studies point to effects on neuroapoptosis and inhibition of synaptogenesis. Should the other side of the age spectrum also concern those of us providing ambulatory dental office-based anesthesia services? Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are recognized complications associated with older patients (≥60 years) undergoing general

Frank HallingMD, DMD, PhD,
Andreas NeffMD, DMD, PhD, and
Thomas ZiebartMD, DMD, PhD
Article Category: Research Article
Volume/Issue: Volume 68: Issue 1
Online Publication Date: Apr 07, 2021
Page Range: 19 – 25

United States and the United Kingdom, lidocaine continues to dominate the market ( Figure 3 ). 2 , 8 A controversial issue is the higher potential neurotoxicity of articaine compared with lidocaine or prilocaine. 23 – 26 In a current systematic review, the included articles present no conclusive evidence to suggest that higher-concentrated 4% articaine causes more nerve damage than 2% lidocaine. 26 Furthermore, in an in vitro study, articaine failed to damage neural cells more than lidocaine. 27 Interestingly, in a randomized double-blind study, lowering

Geraldo Prisco da Silva-JuniorDDS, MSc,
Liane Maciel de Almeida SouzaDDS, MSc, PhD, and
Francisco Carlos GroppoDDS, MSc, PhD
Article Category: Research Article
Volume/Issue: Volume 64: Issue 2
Online Publication Date: Jan 01, 2017
Page Range: 80 – 84

the surgical procedures was adequate to observe the anesthesia success, since pulpal anesthesia is around 1 hour for both amides used here. 34 , 35 All surgeries demanded tooth section and, thus, an adequate pulpal anesthesia, which was obtained in the present study in most of patients. Considering that the use of articaine in the present study was an infiltrative anesthesia after IANB with lidocaine, the potential neurotoxicity was minimized, and no cases of paresthesia were observed, although only a small number of participants were involved. In

Naohiro OhshitaDDS, PhD,
Koji YamagataPhD,
Akio HimejimaDDS, PhD,
Kazuhiro KanedaDDS, PhD,
Teruyuki YasutomeDDS, PhD,
Yoshiko MatsudaDDS, PhD,
Yasuo M. TsutsumiMD, PhD, and
Yoshihiro MomotaDDS, PhD
Article Category: Case Report
Volume/Issue: Volume 67: Issue 4
Online Publication Date: Dec 31, 2020
Page Range: 226 – 229

Pharmacol Exp Ther . 2001 ; 299 : 939 – 944 . 15.  Xu H, Zhao B, She Y, Song X. Dexmedetomidine ameliorates lidocaine-induced spinal neurotoxicity via inhibiting glutamate release and the PKC pathway . Neurotoxicology . 2018

Mark A. SaxenDDS, PhD
Article Category: Research Article
Volume/Issue: Volume 70: Issue 4
Online Publication Date: Jan 15, 2024
Page Range: 206 – 208

general anesthesia, the concern for potential neurotoxicity remains. Iliff HA, Baxter A, Chakladar A, Endlich Y, McGuire B, Peyton J. Airway topicalization in pediatric anesthesia: an international cross-sectional study. Pediatr Anesth . 2023;00:1–8. doi: 10.1111/pan.1478 The primary aim of this cross-sectional study was to determine current international dosing practices for lidocaine airway topicalization in children. The secondary aims included examining aftercare instructions for those receiving lidocaine airway topicalization and