Revista Áquila, n. 35, e35009, 2026
ISSN: 1414-8846 | E-ISSN 2317-6474
DOI: https://doi.org/10.61565/revista-aquila.i35.1069
Neurosensory complications associated with articaine use in dental procedures: a
narrative literature review1
Complicações neurossensoriais associadas ao uso da articaína em procedimentos
odontológicos: uma revisão narrativa da literatura
Complicaciones neurosensoriales asociadas al uso de la articaína en procedimientos
dentales: una revisión narrativa de la literatura
Michelle Alonso Coutinho2
Gabriel Dias de Medeiros3
Marcela Baraúna Magno4
Andréa Vaz Braga Pintor5
ABSTRACT
Local anesthesia is essential for pain control in dentistry; however, neurosensory complications, particularly
paresthesia affecting the lingual and inferior alveolar nerves, remain clinically significant adverse events.
This narrative review critically evaluated the association between 4% articaine and neurosensory
disturbances in dental practice. Methods: A comprehensive search of PubMed, SciELO, LILACS Plus (via
BVS), and Google Scholar was conducted in May 2026. Controlled vocabulary and free-text terms were
combined for articaine/carticaine, adverse drug effects, paresthesia, facial paralysis, formication, and
dysesthesia. Of 320 records identified, 16 studies met predefined PICO-based eligibility criteria after
deduplication and screening. Studies involving articaine combined with other anesthetics, animal models, or
5Graduada em Odontologia pela Faculdade de Odontologia de Nova Friburgo, Especialista em
Odontopediatria pela Associação Brasileira de Odontologia – ABO-RJ, Especialista em Dentística pela
Faculdade de Odontologia São Leopoldo Mandic, Mestre em Odontologia (Clínica Odontológica) pela
Universidade Federal Fluminense – UFF, Doutora em Odontologia (Odontopediatria) pela Universidade
Federal do Rio de Janeiro – UFRJ e Pós-Doutorado pela Universidade Federal do Rio de Janeiro – UFRJ.
E-mail: [email protected]. ORCID: 0000-0002-3323-7691.
4Graduada em Odontologia pela Universidade Federal do Pará – UFPA, Especialista em Prótese Dental pela
Universidade Estadual de Campinas – UNICAMP, Mestre em Odontologia pela Universidade Federal do
Pará – UFPA, Doutora em Odontologia pela Universidade Federal do Rio de Janeiro – UFRJ e Especialista
ORCID: 0000-0003-3618-190X.
3Graduando em Odontologia, pela Universidade Veiga de Almeida. E-mail: [email protected].
ORCID: 0009-0009-6414-7144.
2Graduada em Odontologia pela Faculdade de Odontologia de Campos ods Goytacazes, Especialista em
Cirurgia e Traumatologia Bucomaxilofacial pela Universidade Serra dos Órgãos – UNIFESO, Mestre em
Disfunção Temporomandibular e Dor Orofacial pela Universidade São Leopoldo Mandic – Campinas,
ORCID: 0000-0003-2414-7739.
1 The translation of the article is the sole responsibility of the authors. Translations of excerpts from works
written in another language, when rendered into English, are likewise the responsibility of the authors, unless
a different authorship is declared.
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non-dental settings were excluded. Results: Included studies, published between 1995 and 2026, comprised
pharmacovigilance analyses, randomized clinical trials, and case reports. Pharmacovigilance data suggested
disproportionate reporting of paresthesia after 4% articaine compared with 2% lidocaine, with estimated
incidences of approximately 1:609,000 and 1:1,100,000 injections, respectively, and relative risks up to 3.6
times higher than expected by market share. Conversely, prospective randomized trials did not identify
statistically significant differences in neurotoxicity between articaine and lidocaine. The lingual nerve
accounted for 70–79% of mandibular nerve injuries, possibly owing to its superficial location and
predominantly unifascicular architecture. Most pharmacovigilance studies did not report anesthetic volume,
symptom duration, or adequately control for surgical trauma, injection technique, and anatomical variation.
Evidence from peripheral regional anesthesia in medicine has not demonstrated a reproducible
articaine-specific neurotoxic signal. Conclusions: Current evidence does not support intrinsic, exclusive
neurotoxicity of 4% articaine. Neurosensory complications are likely multifactorial, involving anatomical
vulnerability, needle trauma, injection technique, anesthetic concentration, and administered volume.
Disproportionate reporting may reflect reporting bias, preferential use in complex inflammatory cases, and
procedure-related confounding. Prospective studies with standardized reporting of dose, volume, symptom
duration, and permanent versus temporary injury are needed.
Keywords: Carticaine. Paresthesia. Dental anesthesia. Nerve injury. Neurotoxicity. Pharmacovigilance.
RESUMO
A anestesia local é essencial para o controle da dor na odontologia; no entanto, complicações
neurossensoriais, especialmente a parestesia que afeta os nervos lingual e alveolares inferiores, permanecem
eventos adversos clinicamente significativos. Esta revisão narrativa avaliou criticamente a associação entre
4% de articaína e distúrbios neurossensoriais na prática odontológica. Métodos: Uma busca abrangente no
PubMed, SciELO, LILACS Plus (via BVS) e Google Scholar foi realizada em maio de 2026. Vocabulário
controlado e termos em texto livre foram combinados para articaína/carticaína, efeitos adversos de
medicamentos, parestesia, paralisia facial, formicação e disestesia. Dos 320 registros identificados, 16
estudos atenderam a critérios pré-definidos de elegibilidade baseados em PICO após deduplicação e triagem.
Estudos envolvendo articaína combinada com outros anestésicos, modelos animais ou ambientes não
odontológicos foram excluídos. Resultados: Os estudos incluídos, publicados entre 1995 e 2026, abrangeram
ensaios clínicos randomizados e relatos de casos. Dados de farmacovigilância sugeriram relatos
desproporcionais de parestesia após 4% de articaína em comparação com 2% de lidocaína, com incidências
estimadas de aproximadamente 1:609.000 e 1:1.100.000 injeções, respectivamente, e riscos relativos até 3,6
vezes maiores do que o esperado em termos de participação de mercado. Por outro lado, ensaios
randomizados prospectivos não identificaram diferenças estatisticamente significativas na neurotoxicidade
entre articaína e lidocaína. O nervo lingual representava 70–79% das lesões do nervo mandibular,
possivelmente devido à sua localização superficial e arquitetura predominantemente unifascicular. A maioria
dos estudos de farmacovigilância não relatou volume anestésico, duração dos sintomas ou controle adequado
para trauma cirúrgico, técnica de injeção e variação anatômica. Evidências da anestesia regional periférica na
medicina não demonstraram um sinal neurotóxico específico da articaína reproduzível. Conclusões: As
evidências atuais não apoiam neurotoxicidade intrínseca e exclusiva de 4% de articaína. As complicações
neurossensoriais provavelmente são multifatoriais, envolvendo vulnerabilidade anatômica, trauma por
agulha, técnica de injeção, concentração anestésica e volume administrado. A notificação desproporcional
pode refletir viés de notificação, uso preferencial em casos inflamatórios complexos e confusão relacionada a
procedimentos. São necessários estudos prospectivos com relato padronizado de dose, volume, duração dos
sintomas e lesão permanente versus temporária.
Palavras-chave: Articaína. Parestesia. Anestesia odontológica. Lesão nervosa. Neurotoxicidade.
Farmacovigilância.
RESUMEN
La anestesia local es esencial para el control del dolor en odontología; sin embargo, las complicaciones
neurosensoriales, especialmente la parestesia que afecta a los nervios linguales e inferiores, siguen siendo
eventos adversos clínicamente significativos. Esta revisión narrativa evaluó críticamente la asociación entre
el 4% de la articaína y las alteraciones neurosensoriales en la práctica dental. Métodos: En mayo de 2026 se
realizó una búsqueda exhaustiva en PubMed, SciELO, LILACS Plus (a través de BVS) y Google Scholar. Se
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combinaron vocabulario controlado y términos de texto libre para articaína/carticaína, efectos adversos de
medicamentos, parestesia, parálisis facial, formicación y disestesia. De los 320 registros identificados, 16
estudios cumplieron criterios de elegibilidad predefinidos basados en PICO tras la deduplicación y el cribado.
Se excluyeron estudios que involucraban articaína combinada con otros anestésicos, modelos animales o
entornos no dentales. Resultados: Los estudios incluidos, publicados entre 1995 y 2026, comprendieron
análisis de farmacovigilancia, ensayos clínicos aleatorizados e informes de casos. Los datos de
farmacovigilancia sugirieron una notificación desproporcionada de parestesia tras un 4% de la articaína frente
al 2% de lidocaína, con incidencias estimadas de aproximadamente 1:609.000 y 1:1.100.000 inyecciones,
respectivamente, y riesgos relativos hasta 3,6 veces superiores a los esperados por cuota de mercado. Por el
contrario, los ensayos aleatorizados prospectivos no identificaron diferencias estadísticamente significativas
en la neurotoxicidad entre la articaína y la lidocaína. El nervio lingual representaba entre el 70 y el 79% de
las lesiones del nervio mandibular, posiblemente debido a su ubicación superficial y a su arquitectura
predominantemente unifascicula. La mayoría de los estudios de farmacovigilancia no informaron volumen
anestésico, duración de los síntomas ni un control adecuado para traumatismos quirúrgicos, técnicas de
inyección y variaciones anatómicas. La evidencia de la anestesia regional periférica en medicina no ha
demostrado una señal neurotóxica específica reproducible de la articaína. Conclusiones: La evidencia actual
no apoya una neurotoxicidad intrínseca y exclusiva del 4% de articaína. Las complicaciones neurosensoriales
probablemente sean multifactoriales, implicando vulnerabilidad anatómica, traumatismo por aguja, técnica de
inyección, concentración anestésica y volumen administrado. La notificación desproporcionada puede
reflejar sesgos de reporte, uso preferencial en casos inflamatorios complejos y confusión relacionada con el
procedimiento. Se necesitan estudios prospectivos con informes estandarizados de dosis, volumen, duración
de los síntomas y lesión permanente frente a temporal.
Palabras clave: Carticaine. Parestesia. Anestesia dental. Lesión nerviosa. Neurotoxicidad.
Farmacovigilancia.
INTRODUCTION
Local anesthesia is recognized as the safest and most effective pharmacological
technique for pain management in dentistry, making it indispensable for clinical and
surgical interventions. However, although the overall incidence of serious complications is
extremely low, nerve injuries remain one of the events with the greatest impact on patients’
quality of life and one of the most feared by practitioners (Daubländer; Müller; Lipp,
1997). Such injuries manifest predominantly as paresthesia, dysesthesia, or hyperesthesia,
primarily affecting branches of the trigeminal nerve, with particular involvement of the
inferior alveolar and lingual nerves (Ghafoor et al., 2023). The lingual nerve - and to a
lesser extent, the inferior alveolar nerve - are the most susceptible structures due to their
fascicular characteristics and anatomical location during conventional anesthetic block
procedures (Ghafoor et al., 2023; Renton et al., 2010).
Historically, the etiology of these neurosensory alterations has been attributed to
direct mechanical trauma during needle penetration, compression caused by edema or
intraneural hemorrhage, and the chemical neurotoxicity of anesthetic agents (Pogrel,
2012). Classic studies suggest that any anesthetic solution possesses intrinsic neurotoxic
potential if deposited in direct contact with the nerve bundle, especially within confined
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anatomical spaces (Kim; Kim; Ahn, 2020; Neal et al., 2015). However, the discussion
regarding pharmacological safety intensified with the introduction of higher-concentration
solutions, particularly 4% articaine (Aquilanti et al., 2022; Haas; Lennon, 1995a).
Synthesized in 1969 and widely used since the 1970s, articaine differs from other amides
due to the presence of a thiophene ring in its molecular structure and an additional ester
linkage (Aquilanti et al., 2022; Haas; Lennon, 1995a; Snoeck, 2012; Hassan et al., 2011;
Singh; Koul, 2024). This configuration confers high lipid solubility, exceptional tissue
diffusion capacity, and rapid systemic metabolism by plasma esterases - properties that
ensure superior anesthetic efficacy and a favorable systemic toxicity profile (Snoeck, 2012;
Tan et al., 2023; Yapp; Hopcraft; Parashos, 2011). Epidemiological investigations and
pharmacovigilance reports have suggested a disproportionate correlation between articaine
use and the incidence of persistent paresthesia, fueling an ongoing debate regarding the
drug’s chemical toxicity versus physical trauma caused by the nerve block technique
(Renton et al., 2010; Neal et al., 2015; Hillerup; Jensen; Ersbøll, 2011).
Despite the extensive literature, a gap in clinical consensus remains: while
surveillance studies indicate warning signs, randomized clinical trials often fail to
demonstrate significant differences in safety profiles between articaine and standard
lidocaine (Renton et al., 2010; Piccinni et al., 2015; Martin; Nimmo; Jennings, 2021). This
discrepancy highlights the need for a comprehensive critical analysis that weighs not only
the drug’s pharmacological aspects and the intrinsic neurotoxicity of local anesthetics but
also anatomical variables, the precision of the operative technique, and the reporting bias
(Weber effect) inherent in health surveillance systems.
The objective of this study is to conduct a narrative literature review on the various
neurosensory complications associated with the use of articaine in dental procedures,
investigating possible causes and explanations for their occurrence.
MATERIALS AND METHODS
To conduct this narrative literature review, a search was performed in the electronic
databases PubMed, SciELO, LILACS Plus (via VHL), and Google Scholar on May 26,
2026. Search strategies were adapted to the specific requirements of each database, using
combinations of controlled descriptors (MeSH terms) and free-text keywords.
The primary strategy used in PubMed was: Carticaine[MeSH Terms] OR
Carticain*[Title/Abstract] OR Articain*[Title/Abstract]) AND (((((Drug-Related Side
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Effects and Adverse Reactions[MeSH Terms]) OR (“Drug-Related Side Effects and
Adverse Reactions”[Title/Abstract])) OR ((“paresthesia”[MeSH Terms]) OR
(paresthesia[Title/Abstract]))) OR ((Facial Paralysis[MeSH Terms]) OR (Facial
Paralysis[Title/Abstract]))) OR ((Formication*[Title/Abstract]) OR
(Dysesthesia*[Title/Abstract]))).
For the other databases, a simplified adaptation of these search combinations was
used, focusing on the terms: Articaine, Carticaine, Drug-Related Side Effects and Adverse
Reactions, Paresthesia, Facial Paralysis, Formication, and Dysesthesia. Table 1 presents the
complete search strategy for each database.
Table 1 – Search strategy in the selected databases.
Database
Search Strategy
PubMed
(www.ncbi.nlm.nih.gov/sites/pubmed)
(Carticaine[MeSH Terms] OR Carticain*[Title/Abstract]
OR Articain*[Title/Abstract]) AND (((((Drug-Related
Side Effects and Adverse Reactions[MeSH Terms]) OR
(“Drug-Related Side Effects and Adverse
Reactions”[Title/Abstract])) OR ((“paresthesia”[MeSH
Terms]) OR (paresthesia[Title/Abstract]))) OR ((Facial
Paralysis[MeSH Terms]) OR (Facial
Paralysis[Title/Abstract]))) OR
((Formication*[Title/Abstract]) OR
(Dysesthesia*[Title/Abstract])))
SciELO
(search.scielo.org)
Articaine AND paresthesia OR Facial Paralysis OR
Formication OR Dysesthesia
LILACS Plus
(via BVS – bvsalud.org)
Carticaine OR Articaine AND Drug-Related Side Effects
and Adverse Reactions OR paresthesia OR Facial
Paralysis OR Formication OR Dysesthesia
Google Scholar
(scholar.google.com.br)
Carticaine OR Articaine AND Drug-Related Side Effects
and Adverse Reactions OR paresthesia OR Facial
Paralysis OR Formication OR Dysesthesia
Source: Prepared by the authors (2026).
Eligibility criteria
Inclusion Criteria
To formulate the inclusion criteria, the PICO strategy was adopted, defined as
follows:
• Population (P): Humans undergoing local anesthesia for dental procedures.
• Intervention (I): Dental local anesthesia using the anesthetic agent articaine.
• Control (C): Any other dental local anesthetic solution.
• Outcome (O): Occurrence of neurosensory complications (paresthesia, dysesthesia,
paralysis, hyperesthesia, among others).
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Exclusion Criteria
Studies presenting the following characteristics were excluded:
• Use of articaine in combination with general anesthesia, sedation, other local
anesthetics, or medications;
• Studies involving non-traditional anesthesia methods (e.g., automated systems) or
conducted in non-dental settings;
• Use of topical anesthetics or spray formulations;
• Studies conducted on animals (in vivo models) or in vitro studies;
• Articles that did not report neurosensory alterations in the full text; those in which
the adverse effect appeared only in the abstract proceeded to full-text reading
before exclusion;
• Inappropriate publication types (publications characterized as letters to the editor,
editorials, or expert opinions lacking primary clinical data);
• Duplicate articles.
Study selection and data extraction
The initial search identified 320 records across the consulted databases (PubMed:
83; SciELO: 27; LILACS Plus: 17; Google Scholar: 193). References were exported to and
managed using EndNote software (Clarivate), where initial duplicates were removed.
Subsequently, the dataset was exported to the Rayyan web application, resulting in a total
of 119 unique articles for initial screening.
The first selection phase involved reading titles and abstracts (Ti/Ab); 92 articles
were excluded for failing to meet eligibility criteria, and 4 lacked abstracts and could not
be retrieved in full text. The remaining 23 articles were selected for full-text reading.
During the full-text reading phase, another 4 studies could not be retrieved, and 3 others
were excluded due to various reasons of ineligibility: one article with an unsuitable
publication format, one with a non-matching outcome, and a study by Papadopoulou and
Anastasakis (2022) - which reported paralysis following lingual nerve supplementation
with mepivacaine - thereby violating the exclusion criterion regarding the absence of
association with other local anesthetics following the use of articaine. Ao final de todo o
processo de triagem e da aplicação rigorosa dos critérios, 16 artigos foram mantidos e
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incluídos na síntese qualitativa desta revisão narrativa. A Figura 1 apresenta o fluxograma
de seleção dos estudos.
Figure 1 - Study selection flowchart.
Source: Prepared by the authors (2026). Notes: The initial search identified 320 records across four
databases (PubMed: 83; SciELO: 27; LILACS Plus: 17; Google Scholar: 193). After removing duplicates
using EndNote and Rayyan software, 119 unique articles remained for title and abstract screening. Of these,
92 articles were excluded for failing to meet eligibility criteria, and 4 articles lacked an abstract and could not
be retrieved in full text. The remaining 23 articles were selected for full-text reading. During the full-text
evaluation, 4 additional studies could not be retrieved, and 3 studies were excluded for the following reasons:
unsuitable publication format (n = 1), outcome did not match (n = 1), and use of articaine in combination
with another local anesthetic (mepivacaine supplementation for the lingual nerve) (n = 1). Finally, 16 studies
were included in the qualitative synthesis of this narrative review.
RESULTS
Characteristics of the included studies
This narrative review synthesized evidence from 16 articles selected according to
predefined criteria, published between 1995 and 2026. The methodological profile of the
studies revealed a balanced distribution across different levels of scientific evidence.
Large-scale retrospective studies based on pharmacovigilance databases - such as the FDA
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Adverse Event Reporting System (FAERS) or regional registries - provided the
epidemiological foundation necessary for analyzing incidence in large populations (Garisto
et al., 2010; Gaffen; Haas, 2009). In contrast, prospective controlled clinical trials offered
data on the safety and efficacy of articaine under rigorous clinical conditions, while case
reports allowed for the detailed documentation of rare complications and atypical
anatomical variations (Papadopoulou; Anastasakis, 2022; Dascanio et al., 2026).
Participant demographics and the dental procedures performed covered a broad
spectrum of clinical practice. Most investigations focused on adult patients, although safety
in pediatric populations was addressed in specific efficacy studies (Malamed; Gagnon;
Leblanc, 2001). Interventions ranged from routine restorative and endodontic procedures to
more complex surgeries, such as third-molar extractions - the latter being frequently
associated with reports of nerve injury due to anatomical proximity to neurovascular
bundles (Dascanio et al., 2026).
Incidence and spectrum of neurosensory complications
The incidence of neurosensory complications associated with articaine is classified
in the literature as a rare event, although data vary depending on the collection
methodology and the healthcare system analyzed. Retrospective studies suggest that 4%
articaine carries a relative risk of paresthesia higher than expected based on its market
share - up to 3.6 times greater than that of other anesthetic solutions (Garisto et al., 2010).
However, it is crucial to note that prospective clinical trials have not identified statistically
significant differences in adverse event rates between articaine and lidocaine, suggesting
that the safety profile remains acceptable for routine clinical use (Malamed; Gagnon;
Leblanc, 2001).
The spectrum of injuries reported in the literature encompasses various sensory
manifestations and, to a lesser extent, motor events. Regarding incidence metrics,
retrospective studies indicate a rate of 1 case per 609,000 injections of 4% articaine,
compared to a ratio of 1 per 1,100,000 injections observed for 2% lidocaine (Gaffen; Haas,
2009). Concerning injury types, there is an absolute predominance of paresthesia -
characterized by partial or total loss of sensation - followed by cases of dysesthesia and
hyperesthesia (Moore; Haas, 2010). Additionally, although occurring in isolation, atypical
motor events such as facial nerve paralysis and glossopharyngeal nerve dysfunction have
been documented (Papadopoulou; Anastasakis, 2022).
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Regarding the duration of symptoms, the literature converges on the fact that most
neurosensory alterations are transient, with complete recovery of sensation occurring
within an average period of two to three months. However, the persistence of symptoms
for more than one year characterizes the injury as permanent; this outcome, although
infrequent, is more prevalent with inferior alveolar nerve blocks compared to infiltration
techniques (Hillerup; Jensen; Ersbøll, 2011).
Clinical, anatomical, and pharmacological variables
Analysis of clinical variables reveals a marked anatomical predilection regarding
the recorded complications. The lingual nerve emerges as the most susceptible structure,
affected in approximately 70% to 79% of mandibular nerve injury cases (Garisto et al.,
2010; Kakroudi; Mehta; Millar, 2015). This vulnerability is attributed to its superficial
anatomical location and fascicular structure, making it more prone to direct trauma during
the administration of an inferior alveolar nerve block (IANB). At the level of the
mandibular lingula, the lingual nerve is frequently characterized as unifascicular, whereas
the inferior alveolar nerve exhibits a multifascicular conformation (Pogrel, 2012). This
anatomical distinction implies that any trauma - whether mechanical (caused by the needle)
or chemical (by the solution) - is more likely to compromise the entirety of the lingual
nerve fibers, resulting in more extensive damage.
The anesthetic technique plays a decisive role, given that the vast majority of
neurosensory complications are associated with regional blocks in the mandible. Maxillary
infiltrations rarely result in persistent damage, reinforcing the hypothesis that the
combination of an invasive block technique and the anesthetic’s pharmacology heightens
the risk of injury (Kakroudi; Mehta; Millar, 2015). Furthermore, the absence of significant
reports of paresthesia in the maxilla or in medical contexts - where articaine is widely used
for spinal and epidural anesthesia - supports the hypothesis that the risk is associated with
the inferior alveolar nerve block (IANB) technique within a confined anatomical space,
rather than exclusively with the anesthetic molecule itself (Piccinni et al., 2015). The 4%
concentration of articaine is frequently cited as a contributing factor to chemical
neurotoxicity, given that exposing nerve tissue to higher concentrations of local anesthetic
can induce axonal damage, independent of physical trauma caused by the needle (Hillerup;
Jensen; Ersbøll, 2011; Piccinni et al., 2015). Although articaine exhibits high lipid
solubility and diffusibility - allowing for the use of smaller volumes - the literature debates
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whether its 4% formulation is the primary etiological factor or if mechanical needle trauma
and intraneural hemorrhages are the true causes of paresthesia (Malamed, 2006). To date,
there is no definitive clinical evidence comparing 4% articaine with lower concentrations
in a dental context, and the 4% concentration remains the standard for this anesthetic agent.
A critical point often overlooked in retrospective literature concerns the total
volume of anesthetic administered. Most studies based on pharmacovigilance databases do
not accurately report the number of cartridges used in cases that progressed to paresthesia
(Garisto et al., 2010). This omission is clinically relevant, given that 4% articaine delivers
twice the mass of drug per volume (72 mg/1.8 mL) compared to 2% lidocaine (36 mg/1.8
mL). Thus, the administration of multiple articaine cartridges can result in an excessive
molecular load at the injection site, suggesting that neurotoxicity may be a dose-dependent
phenomenon exacerbated by the drug’s high concentration.
The lingual nerve’s selective vulnerability compared to the inferior alveolar nerve
(IAN) is supported by the fascicular architecture of these structures. The lingual nerve’s
unifascicular pattern - as opposed to the IAN’s multifascicular conformation - means there
is less connective tissue available to dissipate the mechanical energy of the injection or
buffer against chemical insult.4,19 Furthermore, the lingual nerve’s anatomical path -
situated more superficially and potentially under tension during maximum mouth opening -
increases the likelihood of direct contact with the needle (Pogrel, 2012; Malamed, 2006).
In this context, shifting toward a paradigm focused on injection technique precision -
prioritizing trajectories that minimize direct contact with nerve trunks - proves more
critical for clinical success and patient safety than the choice of anesthetic agent alone
(Dascanio et al., 2026; Malamed, 2006).
In addition to sensory complications, the literature documents more severe - albeit
atypical - motor neurological events, such as facial nerve paralysis and glossopharyngeal
nerve dysfunction. These episodes generally occur due to anatomical variations or
retrograde flow of the anesthetic agent (Papadopoulou; Anastasakis, 2022). The classic
mechanism underlying temporary facial paralysis involves the inadvertent injection of the
anesthetic solution into the parotid gland capsule, allowing the drug to diffuse through the
cervical fasciae and reach branches of the seventh cranial nerve. Articaine’s high
diffusibility, a result of its molecular structure, can facilitate this unwanted spread if the
regional block technique is not performed with strict adherence to anatomical landmarks.
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Although these events are typically transient and self-limiting, they underscore the
need for caution when administering an inferior alveolar nerve block and highlight the
importance of negative aspiration to prevent intravascular or glandular deposition of the
drug (Papadopoulou; Anastasakis, 2022; Malamed, 2006).
DISCUSSION
The primary etiology of neurosensory injuries associated with the use of articaine
remains a central topic of debate in dental literature. A critical analysis of the evidence
indicates that, although articaine demonstrates clinical efficacy comparable to that of other
amide-type anesthetics, there is no consensus in the literature regarding its direct
neurotoxicity, given that many reports of paresthesia stem from multifactorial causes, such
as anesthetic technique and anatomical variability (Dascanio et al., 2026). The discussion
centers on the distinction between direct mechanical trauma caused by the needle - which
can result in intraneural or extraneural hemorrhage and inflammatory processes arising
from edema at the injection site - and the potential chemical neurotoxicity of the drug itself
(Malamed, 2006).
Molecular properties and neurotoxic potential
The unique molecular properties of articaine are fundamental to understanding its
neurotoxic potential. The presence of a thiophene ring in its structure - replacing the
conventional benzene ring - confers high lipid solubility and a rapid rate of tissue diffusion
(Malamed; Gagnon; Leblanc, 2001). Although these characteristics enhance the depth of
anesthesia, research suggests that the increased risk of paresthesia may be correlated with
the high concentration (4%) of articaine solutions, reinforcing the premise that clinical
safety is intrinsically linked to dosage control (Gaffen; Haas, 2009). The hypothesis that
the direct neurotoxicity of 4% articaine contributes to axonal alterations through prolonged
contact lacks definitive mechanistic confirmation in the literature; however, the warning
signal is more pronounced for this agent and for prilocaine compared to other anesthetics at
lower concentrations (Piccinni et al., 2015).
Comparative *in vitro* studies indicate that articaine does not exhibit inherently
higher cytotoxicity than other local anesthetics when evaluated at equimolar
concentrations. The clinical warning signal appears to be strictly linked to its commercial
4% formulation, which exposes neural tissue to a significantly higher solute concentration
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(Malamed; Gagnon; Leblanc, 2001). It is also important to distinguish between temporary
and permanent damage, as most reports do not specify the exact duration of symptoms,
although the literature indicates that spontaneous recovery occurs in the vast majority of
cases within a period of 8 to 12 weeks (Hillerup; Jensen; Ersbøll, 2011).
Evidence on regional anesthesia in medicine
Although articaine has historically been associated with reports of paresthesia in
dentistry - particularly following inferior alveolar nerve block (IANB) - evidence from
other medical specialties raises important questions regarding whether these events are
attributable to the anesthetic itself or to procedure-specific factors. Articaine has been
successfully used for peripheral nerve blocks in medicine, including axillary and
interscalene brachial plexus blocks, digital nerve blocks, and ophthalmic regional
anesthesia (Soeck, 2012; Lakhin et al., 2025). Clinical studies comparing articaine with
other local anesthetics have demonstrated favorable anesthetic efficacy, with no increase in
the incidence of persistent neurological complications. For instance, in a prospective,
randomized study on brachial plexus blocks, Lakhin et al. (2025) reported no permanent
sensory deficits or neuropathies attributable to articaine, despite its direct administration
around major peripheral nerves. Similarly, Ertikin et al. (2017) observed no neurological
complications associated with articaine during axillary brachial plexus blocks for hand
surgery.
It is important to note that neurological complications following peripheral nerve
blocks are well-recognized in anesthesiology, regardless of the local anesthetic used. Large
prospective studies and systematic reviews (Neal et al., 2015; Borgeat et al., 2001; Brull et
al., 2007) have demonstrated that postoperative paresthesia, hypoesthesia, and transient
motor deficits can occur following regional anesthesia with lidocaine, bupivacaine,
mepivacaine, ropivacaine, and other agents. These complications are generally considered
multifactorial, with the primary injury mechanisms being needle trauma, intraneural
injection, high injection pressure, hematoma formation, ischemia, compression,
postoperative inflammation, and patient-related anatomical factors (Neal et al., 2015;
Borgeat et al., 2001). Consequently, contemporary anesthesiology literature does not
attribute the majority of neurological complications to the intrinsic neurotoxicity of a
specific anesthetic molecule.
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This contrasts with dental literature, in which articaine - particularly at a 4%
concentration - has been disproportionately associated with reports of lingual and inferior
alveolar nerve paresthesia (Haas; Lennon, 1995a; Monteiro et al., 2015). However, most of
this evidence stems from spontaneous adverse event reports, retrospective case series, and
pharmacovigilance databases, which are inherently incapable of establishing causality.
Furthermore, a similar association has not been consistently demonstrated in randomized
clinical trials or prospective comparative studies evaluating neurological outcomes.
Anatomical and technical considerations
The anatomical and technical characteristics of the inferior alveolar nerve block
may partially explain this discrepancy. Unlike most peripheral nerve blocks performed in
modern anesthesiology, the inferior alveolar nerve block is typically performed using
anatomical landmarks, without direct visualization of the nerve. Consequently, inadvertent
needle contact with the nerve, intrafascicular injection, high injection pressures, or
localized hematoma formation may occur more frequently. Furthermore, the lingual nerve
- identified by Pogrel (2007) as responsible for the majority of reported cases of
post-anesthetic paresthesia in dentistry - appears particularly susceptible due to its
superficial location, relatively limited connective tissue protection, and lower fascicular
complexity compared to many peripheral nerves. These anatomical characteristics may
increase its vulnerability to mechanical injury, regardless of the anesthetic solution
administered.
Experimental evidence also challenges the hypothesis of articaine-specific
neurotoxicity. In vitro and animal studies, such as those by Hillerup and Jensen (2006) and
Radwan, Saito, and Goto (2002), have revealed that all amide-type local anesthetics exhibit
concentration-dependent neurotoxic effects when neural tissue is exposed to sufficiently
high concentrations. Although articaine has occasionally demonstrated cytotoxic effects
comparable to those of other agents, there is no consistent evidence indicating that it is
intrinsically more neurotoxic than lidocaine, mepivacaine, or bupivacaine when evaluated
under equivalent experimental conditions. The observation that 4% prilocaine was also
associated with paresthesia reinforces the hypothesis that the anesthetic concentration -
rather than the specific molecule - may contribute to nerve injury when combined with
unfavorable procedural circumstances (Haas; Lennon, 1995a; 2000).
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Pharmacovigilance biases and the Weber Effect
Interpreting epidemiological data on articaine requires extreme caution due to the
methodological limitations of the studies reviewed. Many investigations rely on
retrospective case reports and pharmacovigilance systems that lack robust control groups,
making it difficult to precisely distinguish between mechanical traumatic injuries and the
chemical neurotoxicity inherent to the drug (Hillerup; Jensen; Ersbøll, 2011; Senes et al.,
2015). The voluntary nature of these reports often results in underreporting, limiting the
accurate calculation of the true incidence of these complications (Gaffen; Haas, 2009).
Furthermore, the rarity of these events hinders the conduct of randomized clinical
trials with sufficient statistical power to detect significant differences, rendering the direct
association between articaine and persistent neurotoxicity inconclusive (Moore; Haas,
2010; Kakroudi; Mehta; Millar, 2015). Factors such as the “Weber effect” must also be
considered, as articaine’s increased market visibility may have artificially inflated the
incidence of reports compared to traditional anesthetics (Piccinni et al., 2015). As it
established itself as a new clinical standard, articaine underwent much more rigorous
scrutiny than traditional agents, which may have introduced confirmation bias into
voluntary reports (Gaffen; Haas, 2009).
Additionally, a clear selection bias is observed in clinical practice: articaine is
frequently the drug of choice for highly complex procedures or cases involving acute
inflammation (“hot teeth”) – situations where achieving anesthetic success is more
challenging (Dascanio et al., 2026). In these scenarios, surgical trauma, local edema, and
instrumentation may be the actual causes of nerve compression, with paresthesia being
erroneously attributed to the anesthetic agent used.
Synthesis of evidence and clinical implications
Taken together, the available evidence suggests that post-anesthetic paresthesia
should be considered a multifactorial event resulting from the interaction of anatomical
vulnerability, injection technique, mechanical trauma, local inflammatory responses,
hematoma formation, injection pressure, anesthetic concentration, and, possibly, individual
patient susceptibility. Therefore, although practitioners should remain alert to the rare
occurrence of neurosensory complications following dental local anesthesia, current
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evidence does not support the conclusion that articaine alone is responsible for these
events.
In clinical practice, the safety of articaine depends primarily on the rigorous
refinement of injection technique and dose control. Shifting to a paradigm focused on
injection technique precision – prioritizing trajectories that minimize direct contact with
nerve trunks, consistent use of negative aspiration, and limitation of the administered
volume – proves more critical to clinical success and patient safety than the choice of
anesthetic agent alone (Dascanio et al., 2026; Kakroudi, Mehta; Millar, 2015).
Critical issues and evidence gaps
Several critical issues emerge from this analysis and warrant explicit consideration.
First, regarding the volume of anesthetic injected: most studies do not report the number of
cartridges administered to patients who developed paresthesia or paralysis. Given that
articaine requires fewer cartridges than lidocaine for an effective inferior alveolar nerve
block (IANB), the question arises as to whether an excessive number of articaine cartridges
- rather than the drug itself - might be the cause of the paresthesia. The potential
involvement of the vasoconstrictor in neurosensory alterations, potential cartridge
contamination, or the influence of anesthesia duration (the time required for the patient’s
body to eliminate the anesthetic) also remain underexplored.
Second, the selective vulnerability of the lingual nerve compared to the inferior
alveolar nerve, along with the absence of reports regarding neurosensory alterations in the
maxilla, argues against the hypothesis of primary chemical neurotoxicity. If the anesthetic
itself were the primary cause, one would expect neurosensory complications to be
distributed more evenly across injection sites, which is not the case. Similarly, the lack of
consistent reports of paresthesia associated with articaine use in medical regional
anesthesia undermines the hypothesis that this drug possesses a unique neurotoxic profile.
Third, the temporal classification of the injuries remains problematic. How many of
the reported cases of paresthesia/paralysis were permanent (persisting for more than 8
weeks), and how many were transient? The lack of specificity in reports regarding whether
the neurosensory damage is temporary or permanent represents a significant limitation of
the current evidence base. The absence of reports must also be taken into account in any
balanced risk assessment. Fourth, when evaluating the total amount of articaine
administered worldwide compared to other anesthetics, it remains unclear whether the
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incidence of paresthesia is genuinely higher than that observed with other agents. The
potential role of campaigns encouraging the reporting of adverse events - and the “Weber
effect”- in generating “fear” of articaine raises the possibility that reporting bias has been
progressively accepted as fact within certain segments of the dental community.
Finally, a possible confounding factor is the preferential use of articaine in more
complex procedures: those involving pre-existing inflammation or causing local
inflammation; those requiring longer operating times - leading to local edema and nerve
compression; or those involving nerve manipulation or potential local hemorrhage
resulting in nerve trauma. These procedure-related factors, rather than the anesthetic agent
itself, may represent the true underlying etiology in a significant proportion of reported
cases.
Limitations of this review
This narrative review has limitations that should be acknowledged. As it is a
narrative rather than a systematic review, the selection of studies – while guided by
predefined criteria – did not follow a fully systematic protocol involving independent,
duplicate screening of all records. Restricting the scope to publications in English and
Portuguese may have excluded relevant studies published in other languages. Furthermore,
the heterogeneity of study designs, outcome definitions, and reporting standards among the
included studies precluded a quantitative synthesis. Finally, the review is limited by the
quality of the primary evidence base, which is predominantly retrospective and
observational.
Current literature does not support the hypothesis of intrinsic and exclusive
neurotoxicity associated with 4% articaine. Evidence - supported by the drug’s safe use in
medical regional anesthesia - indicates that neurosensory complications in dentistry
(predominantly lingual nerve paresthesia) have a multifactorial etiology.
Such events stem primarily from the anatomical vulnerability of the lingual nerve
(particularly its unifascicular architecture within the pterygomandibular space), the
mechanical trauma inherent to the inferior alveolar nerve block (IANB) technique, and the
confined anatomical space where the injection is administered. These factors may be
exacerbated by the drug’s high concentration (4%) and the volume administered, but they
are not caused exclusively by the articaine molecule itself.
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The disproportionate reporting of paresthesia associated with articaine in
pharmacovigilance systems may be partially explained by: (1) the Weber effect, whereby
newly introduced drugs or those gaining academic prominence generate an increase in
adverse event reports; (2) selection bias, given that articaine is preferentially used in
complex surgical cases involving pre-existing inflammation; (3) confounding by
procedure-related factors, such as surgical trauma, edema, and instrumentation; and (4) the
lack of standardized documentation regarding the administered volume and the temporal
classification of the injuries (temporary versus permanent).
The absence of a reproducible signal of neurosensory complications associated with
the use of articaine in medical regional anesthesia - a setting in which the drug is
administered near major peripheral nerves under ultrasound guidance - further weakens the
hypothesis of a neurotoxic profile unique to articaine and reinforces the role of
technique-related factors in dental complications.
CONCLUSION
In summary, clinical safety with articaine depends primarily on the rigorous
refinement of injection technique (including precise identification of anatomical
landmarks, performance of negative aspiration, slow injection, and minimization of the
administered volume) and on dose control. Well-designed prospective randomized studies
with standardized outcome reporting - including clear documentation of the number of
cartridges administered, a distinction between temporary and permanent injuries, and
systematic assessment of confounding variables - are needed to definitively distinguish
traumatic from chemical nerve injuries in dental practice. Until such evidence is available,
the clinical approach should prioritize injection precision and dose limitation over the
choice of a specific anesthetic agent.
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License: CC BY-NC-ND 4.0 – Attribution-NonCommercial-NoDerivatives 4.0 International
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