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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

have associated the use of 4% articaine with 1:100,000 epinephrine with a higher, albeit relatively rare, incidence of paresthesia, following inferior alveolar nerve block than 2% lidocaine with 1:100,000 epinephrine. 4 , 8 An additional study reported that articaine was shown to contribute to more than a 20-fold increase in reported paresthesia compared with all other local anesthetics combined. 9 Nonsurgical cases of paresthesia in dentistry are almost exclusively related to inferior alveolar nerve block injection and appear to affect the lingual nerve more

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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.


Caroline McCarthyBDS, MFDS,
Paul BradyBDS, MFDS, MSc, ConSed,
Ken D. O'HalloranBSc, PhD, and
Christine McCrearyMA, MD, FDS(OM), RCPS, FFD, RCSI
Article Category: Case Report
Volume/Issue: Volume 63: Issue 1
Online Publication Date: Jan 01, 2016
Page Range: 25 – 30

alkalosis. Consequences of hyperventilation can include paresthesia of the extremities, muscle rigidity, dizziness and fainting. Cardiovascular disturbances include palpitations and chest oppression and pain can also be experienced. Although administration of benzodiazepines such as midazolam offers anterograde amnesia, stress reduction and reassurance are important for the prevention of hyperventilation. Cognitive behavioral therapy has been shown to have a longer-lasting positive effect on patient attitude to the dentist than the administration of

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

. Local anesthetics can produce direct toxicity to nerve trunks, leading to persistent paresthesias. Although the dental community has been slow to reach consensus regarding this issue, it should be appreciated that medical anesthesia literature is emphatic in claiming that greater concentration of local anesthetic solutions increases risk for direct neurotoxicity to nerve trunks: “All the clinically used local anesthetics can produce direct toxicity to nerves if they achieve sufficiently high intraneural concentrations. Clinicians should be aware that

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

after IANB. 15 Since articaine introduction in the market, it has been compared to a number of local anesthetics. Despite reports on articaine safety in comparison with lidocaine in both adults and children, 2 a possible relationship between paresthesia and articaine has been suggested. 16 The main cause of the paresthesia is not completely understood, but it could be related to the higher concentration of local anesthetic agent. The possibility of paresthesia has led to suggestions to avoid the use of high-concentration anesthetic formulations for nerve

Daniel E. BeckerDDS and
Kenneth L. ReedDMD
Article Category: Research Article
Volume/Issue: Volume 53: Issue 3
Online Publication Date: Jan 01, 2006
Page Range: 98 – 109

of paresthesia after its use for inferior alveolar blocks. Haas and Lennon 14 reported an increased incidence of paresthesias in Canada after the introduction of articaine in the mid 1980s. In 1993 alone, 14 cases of paresthesia were reported, and all were attributed to articaine or prilocaine (see Table 3 ). Although the overall incidence of paresthesia is low, one cannot discount the increased risk that is apparently associated with higher concentrations of local anesthetics when used for nerve blocks. Table 3. Incidence

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

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

the concentration of articaine from 4% to 2% did not affect the onset of action, the local anesthetic effect, or the postoperative complications. However, the duration of soft-tissue anesthesia was shortened by nearly half an hour, which was statistically significant. 28 In addition to articaine, prilocaine is also solely available in dental cartridges as a 4% solution, the highest concentration among injectable dental local anesthetics. In a retrospective review of voluntary reports of nonsurgical paresthesias, the observed frequencies of paresthesias for

Lindsay PabstDDS, MS,
John NussteinDDS, MS,
Melissa DrumDDS, MS,
Al ReaderDDS, MS, and
Mike BeckDDS, MA
Article Category: Research Article
Volume/Issue: Volume 56: Issue 4
Online Publication Date: Jan 01, 2009
Page Range: 128 – 134

paresthesia associated with articaine use has been reported, 16 – 18 no subjects reported any paresthesia in our study even though the injection site approximated the mental nerve. In conclusion, repeated infiltration of a cartridge of 4% articaine with 1∶100,000 epinephrine given 25 minutes after an initial infiltration of the same type and dose of anesthetic significantly improved the duration of pulpal anesthesia when compared with only an initial infiltration in the mandibular first molar. REFERENCES 1