Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version


Publication Source

Anesthesia Progress





Start Page


Last Page





The local anesthetics lidocaine and articaine are among the most widely used drugs in the dentist’s arsenal, relieving pain by blocking voltage-dependent Naþ channels and thus preventing transmission of the pain signal. Given reports of infrequent but prolonged paresthesias with 4% articaine, we compared its neurotoxicity and functional impairment by screening cultured neural SH-SY5Y cells with formulations used in patients (2% lidocaine + 1:100,000 epinephrine or 4% articaine + 1:100,000 epinephrine) and with pure formulations of the drugs. Voltage-dependent sodium channels Na(v)1.2 and Na(v)1.7 were expressed in SH-SY5Y cells. To test the effects on viability, cells were exposed to drugs for 5 minutes, and after washing, cells were treated with the ratiometric Live/Dead assay. Articaine had no effect on the survival of SH-SY5Y cells, while lidocaine produced a significant reduction only when used as pure powder. To determine reversibility of blockage, wells were exposed to drugs for 5 minutes and returned for medium for 30 minutes, and the calcium elevation induced by depolarizing cells with a high-potassium solution was measured using the calcium indicator Fura-2. High potassium raised calcium in control SH-SY5Y cells and those treated with articaine, but lidocaine treatment significantly reduced the response. In conclusion, articaine does not damage neural cells more than lidocaine in this in vitro model. While this does not question the safety of lidocaine used clinically, it does suggest that articaine is no more neurotoxic, at least in the in vitro setting. © 2018 by the American Dental Society of Anesthesiology.


Articaine, Calcium, Delayed responsiveness, Lidocaine, Neurons, Neurotoxicity, Paresthesia, Sodium channel, Anesthetics, Local, Calcium Signaling, Carticaine, Cell Line, Tumor, Cell Survival, Humans, Lidocaine, NAV1.2 Voltage-Gated Sodium Channel, NAV1.7 Voltage-Gated Sodium Channel, Neurons, Neurotoxicity Syndromes, Risk Assessment, Time Factors, Voltage-Gated Sodium Channel Blockers, articaine, lidocaine, local anesthetic agent, SCN2A protein, human, SCN9A protein, human, sodium channel Nav1.2, sodium channel Nav1.7, voltage gated sodium channel blocking agent, calcium signaling, cell survival, comparative study, drug effect, human, metabolism, nerve cell, pathology, risk assessment, time factor, toxicity and intoxication, tumor cell line



Date Posted: 10 February 2023

This document has been peer reviewed.