UNIVERSIDADE ESTADUAL PAULISTA
“JÚLIO DE MESQUITA FILHO”
Instituto de Ciência e Tecnologia
Campus de São José dos Campos
ORIGINAL ARTICLE DOI: https://doi.org/10.4322/bds.2024.e4060
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Braz Dent Sci 2024 Jan/Mar;27 (1): e4060
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Influence of root canal sealer composition on postoperative pain
after endodontic treatment of permanent teeth: a systematic
review and meta-analyses
Influência da composição do cimento endodôntico na dor pós-operatória de dentes permanentes tratados
endodonticamente: uma revisão sistemática e meta-análise
Vânia Gomes MORAES1 , Sandra Regina Santos MEYFARTH2 , Guido Artemio MARAÑÓN-VÁSQUEZ3 ,
Lívia Azeredo Alves ANTUNES4 , Leonardo Santos ANTUNES4
1 - Universidade Federal Fluminense, Faculdade de Odontologia. Nova Friburgo, RJ, Brazil.
2 - Universidade Federal Fluminense, Faculdade de Odontologia. Niterói, RJ, Brazil.
3 - Universidade Federal do Rio de Janeiro, Faculdade de Odontologia. Rio de Janeiro, RJ, Brazil.
4 - Universidade Federal Fluminense, Faculdade de Odontologia de Nova Friburgo, Departamento de Formação Especíca. Nova
Friburgo, RJ, Brazil.
How to cite: Moraes VG, Meyfarth SRS, Marañón Vásquez GA, Antunes LAA, Antunes LS. Inuence of root canal sealer composition
on postoperative pain after endodontic treatment of permanent teeth: a systematic review and meta-analyses. Braz Dent Sci. 2024;
27(1):e4060. https://doi.org/10.4322/bds.2024.e4060
ABSTRACT
Postoperative pain is a frequent complication after root canal treatment. Its management is an important aspect of
endodontic practice. Some treatment-related parameters were associated with the development of postoperative
pain, including the sealer composition and extrusion. Objective: This systematic review aimed to answer the
clinical question: Do root canal sealers composition inuence postoperative pain after endodontic treatment of
permanent teeth? Material and Methods: Electronic searches were conducted in PubMed, Scopus, Web of Science,
Cochrane, LILACS, and grey literature databases until September 2021. The studies were qualitatively assessed
using the RoB2 tool (Cochrane) and the certainty of evidence (GRADE). Sensitivity and pooled estimates were
calculated using a random-effects model. Twelve articles were included. Results: The risk of bias was high in
one study, low in nine, and two had some concerns. Qualitative analyses showed no inuence of sealer extrusion
on postoperative pain. Meta-analyses showed no signicant difference in postoperative pain with moderate to
very low levels of certainty between AH Plus and calcium silicate-based sealers, in a 95% condence interval.
Analysis between AH Plus, Zinc Oxide and Eugenol (ZOE), and calcium hydroxide (Ca(OH)2)-based sealers
were not performed due to heterogeneity and lack of data. Conclusion: Literature showed contrasting results
in postoperative pain between AH Plus and ZOE-based sealers, with low to moderate certainty of evidence.
Regarding Ca(OH)2-based sealers, a single study with a low level of certainty concluded that AH Plus presented
less postoperative pain than Apexit Plus. Therefore, further studies are needed to assess the inuence of these
sealers on postoperative pain. Evidence showed no difference in postoperative pain between AH Plus and calcium
silicate-based sealers. Sealer extrusion is a variable that requires further studies.
KEYWORDS
Postoperative pain; Root canal treatment; Sealer composition; Sealer extrusion; Systematic review.
RESUMO
A dor pós-operatória é uma complicação frequente após o tratamento endodôntico. O seu manejo é um
importante aspecto na prática endodôntica. Algumas variáveis relacionados ao tratamento foram associados
com o desenvolvimento da dor pós-operatória, incluindo a composição e extrusão dos cimentos endodônticos.
Objetivo: Esta revisão sistemática objetivou responder a seguinte pergunta clínica: A composição dos cimentos
endodônticos podem inuenciar a dor pós-operatória de dentes permanentes tratados endodonticamente?
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Braz Dent Sci 2024 Jan/Mar;27 (1): e4060
Moraes et al.
Influence of root canal sealer composition on postoperative pain after endodontic treatment of permanent teeth: a systematic review and meta-analyses
Moraes et al. Influence of root canal sealer composition on postoperative
pain after endodontic treatment of permanent teeth: a
systematic review and meta-analyses
INTRODUCTION
Postoperative pain is a frequent complication
after root canal treatment and such condition may
have an impact on patients quality of life [1].
Generally, it ranges from mild to moderate
and occurs even after optimal procedures are
performed [2]. However, pain control remains a
key issue in endodontic treatment [3].
Pain is multifactorial in nature [4] and
can be induced by mechanical, chemical, or
microbiological injuries to the periodontal
tissues [5]. Endodontic sealers may affect the
periradicular tissues either by direct contact or by
percolating components that are released through
the root canal systems [6] which may trigger
an inammatory response increasing the risk of
postoperative pain [7]. Such sealers are developed
to be inside the root canal system. However,
unintentional extrusion may occur [8] thus
causing symptoms such as pain, hyperesthesia,
and paresthesia [9]. These symptoms may vary
in intensity depending on the amount of extruded
sealer [10].
A wide variety of root canal sealers are
currently available in the market. Of these,
Zinc Oxide and Eugenol (ZOE)-based, calcium
hydroxide (Ca(OH)2)-based, glass ionomer,
mineral trioxide aggregate, and resin-based sealers
are commonly used. Additionally, bioceramic
sealers have recently been launched [6,11].
Histological ndings indicate that components
percolated from the root canal sealers may induce
local inammatory effects [12] and its intensity is
related to the sealer composition [6]. Dysregulated
cytokine production during inflammatory
processes is a potential contributor to the
development of inflammatory diseases [13].
Interleukin-6 (IL-6) and (IL-8) release have been
reported to play an important role in root canal
sealer-induced periapical inammation [13,14].
Two systematic reviews [15,16] evaluated
the risk and intensity of postoperative pain with
calcium silicate and epoxy resin-based sealers,
but not with other types of sealers. Additionally,
both studies presented contrasting results.
Sponchiado et al. [15] showed no statistical
difference between the composition and pain
between these two sealers. Mekhdieva et al. [16]
concluded that calcium silicate-based sealers
were associated with signicantly lower pain than
epoxy resin-based sealers.
Therefore, this systematic review aimed
to investigate current evidence regarding the
inuence of other types of sealers composition
on postoperative pain after endodontic treatment.
The clinical question was designed according
to the Population, Intervention, Comparator,
Outcome, and Study (PICOS) and should answer
the following clinical question: Do root canal
sealer composition inuence postoperative pain
after endodontic treatment of permanent teeth?
MATERIAL AND METHODS
This systematic review and meta-analysis was
conducted according to the Preferred Reporting
Material e Métodos: Buscas eletrônicas foram realizadas nas bases de dados no PubMed, Scopus, Web of Science,
Cochrane, LILACS, e literatura cinzenta até setembro de 2021. Os estudos foram avaliados qualitativamente usando
a ferramenta RoB2 (Cochrane) e a certeza de evidência (GRADE). A sensibilidade e as estimativas agrupadas
foram calculadas usando um modelo de efeitos aleatórios. Doze artigos foram incluídos. Resultados: O risco de
viés foi alto em um estudo, baixo em nove e dois tiveram algumas preocupações. A análise qualitativa mostrou
que não há inuência da extrusão do cimento na dor pós-operatória. A meta-análise mostrou que não houve
diferença estatisticamente signicante na dor pós-operatória entre o AH Plus e os cimentos a base de silicato de
cálcio com moderada a muito baixa certeza de evdência. Análises entre os cimentos AH Plus, óxido de zinco e
eugenol (OZE) e hidróxido de cálcio não foram realizados devido a heterogeneidade e falta de dados. Conclusão:
A literatura sugere resultados contrastantes com relação a dor pós-operatória e entre os cimentos AH Plus e OZE,
com baixa a moderada certeza de evidência. Já os cimentos a base de hidróxido de cálcio, um único estudo com
baixa certeza de evidência concluiu que o AH Plus apresentou menos dor pós tratamento endodôntico do que
o Apexit Plus. Portanto,mais estudos são necessários para avaliar a inuência desses tipos de cimentos na dor
pós-operatória. Com relação ao cimento AH Plus e os cimentos a base de silicato de cálcio não houve diferença
estatística entre eles e a dor. A extrusão dos cimentos é uma variável que requer mais estudos.
PALAVRAS-CHAVE
Dor pós-operatória; Tratamento endodôntico; Composição dos cimentos; Extrusão dos cimentos; Revisão sistemática.
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Braz Dent Sci 2024 Jan/Mar;27 (1): e4060
Moraes et al.
Influence of root canal sealer composition on postoperative pain after endodontic treatment of permanent teeth: a systematic review and meta-analyses
Moraes et al. Influence of root canal sealer composition on postoperative
pain after endodontic treatment of permanent teeth: a
systematic review and meta-analyses
Items for Systematic Reviews and Meta-analysis
(PRISMA) statement [17] and was registered in
the PROSPERO database (CRD42020211297).
Eligibility criteria
The inclusion criteria was outlined according
to the Population, Interventions, Comparisons,
Outcomes, and Studies. The articles should
answer the following PICOS, as follow:
(P) Population included patients undergoing
nonsurgical root canal treatment in
permanent teeth;
(I) Intervention included root canal lling with
AH Plus sealer with or without extrusion;
(C) Comparison included root canal filling
with other types of sealer with or without
extrusion;
(O) Outcome included postoperative pain after
root canal treatment;
(S) Study design included randomized controlled
trials (RCTs).
Exclusion criteria
Duplicated articles, pilot studies, literature
reviews, editorial letters, book chapters, theses
and guidelines were excluded.
Search strategy and study selection
An electronic search was conducted to
identify relevant articles. No restrictions were
imposed on the dates. Studies published in
English, Portuguese and Spanish were included.
The following databases were searched until
September 29, 2021: PubMed, Scopus, Web
of Science, Cochrane, LILACS, and OpenGrey.
In addition, MeSH terms, synonyms, and free
terms were used and combined to refine the
search results, as presented in Table I. Experts
were contacted to identify related unpublished
and ongoing studies. The records were exported
to Mendeley (Mendeley Ltd., UK, England);
duplicates were considered only once.
Before analyzing the selected abstracts, a
Kappa test was conducted to evaluate agreement
among evaluators (10% of the publications
were randomly selected). Subsequently, their
classifications were compared, resulting in a
kappa statistic of 0.90. All potentially relevant
publications were selected by reading the titles
and abstracts by two independent reviewers
(VM and SM). Any differences between them
were resolved by consensus with the third
author (LSA). Studies without abstracts were
also assessed for inclusion. Subsequently, the
full texts of all potentially eligible studies were
accessed; inclusion and exclusion criteria were
then applied. Any other disagreements were
resolved by consensus with the senior reviewer
(LSA). Additionally, the reference lists of the
included studies were manually searched to
retrieve all eligible articles.
Data extraction
Data were extracted by two independent
authors (VM and SM) and organized as follows:
1. First author, year of publication;
2. Sample (sample size, gender, tooth type,
tooth diagnosis);
3. Endodontic treatment (irrigation,
instrumentation, number of sessions,
obturation technique, type of sealer);
4. Preoperative symptoms;
5. Pain assessment (pain scale, period in hours,
and analgesic intake);
6. Postoperative symptoms;
7. Results.
Risk of bias
The RoB2 tool was used for assessing the
risk of bias (RoB) of the selected RCTs [18].
Two authors (LSG and SM) independently
assessed the RoB of the included studies in a
duplicate manner. Disagreements were resolved
by consensus with the senior reviewer (LSA).
If relevant data were missing, the authors were
contacted. The sources of bias assessed were
the randomization process, deviations from the
intended intervention, missing outcome data,
measurement of the outcome, and selection of
the reported result. Each domain was classied
as having low (+), high (x), or some concerns (-)
RoB. A study was considered to have an overall
high RoB if judged to be at high RoB in at least
one domain or judged to have “some concerns”
for multiple domains in a way that substantially
lowers confidence in the result. A study was
considered to have an overall some concerns RoB
if judged to be at “some concerns” in at least one
domain. Finally, a study was considered to have
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Moraes et al.
Influence of root canal sealer composition on postoperative pain after endodontic treatment of permanent teeth: a systematic review and meta-analyses
Moraes et al. Influence of root canal sealer composition on postoperative
pain after endodontic treatment of permanent teeth: a
systematic review and meta-analyses
an overall low RoB if judged to be at low RoB for
all domains [18].
Meta-analysis
A meta-analysis was performed to combine
comparable results using subgroup analysis.
Extraction data of the mean and the standard
deviation with 95% confidence interval (CI)
related to the post-operative pain between the
types of sealer groups in the time intervals of
6, 12, 24, 48, and 72 hours were performed.
A random effects model was used in the meta-
analysis. The mean differences between the sealer
groups were determined using inverse variance
meta-analysis. I2 was used to assess the statistical
heterogeneity between studies, where values of
25%, 50%, and 75% indicated low, medium,
and high heterogeneity, respectively [19].
Meta-analysis and forest plots were performed
using the RevMan 5.4. Sensitivity analyses
using different methods of data imputation and
subgroup analyses were also planned.
Evidence synthesis (GRADE)
The Grading of Recommendations
Assessment, Development, and Evaluation
(GRADE) system for classifying the certainty of
the evidence was used to ensure the accuracy
of data analysis. GRADE Pro GDT software
(http://gdt.guidelinedevelopment.org) was
used to summarize the results. Certainty is
downgraded owing to RoB, inconsistency,
Table I - Electronic Databases and Search Strategy
Pub Med
n=463
(((((((((((((root canal therapy[MeSH Terms]) OR (root canal therapy[Title/Abstract])) OR (teeth, endodontically
treated[MeSH Terms])) OR (teeth, endodontically treated[Title/Abstract])) OR (endodontically-treated tooth[MeSH
Terms])) OR (endodontically-treated tooth[Title/Abstract])) OR (root canal preparation[MeSH Terms])) OR (root canal
preparation[Title/Abstract])) OR (tooth root therapy[Title/Abstract])) OR (endodontic therapy[Title/Abstract])) OR
(endodontic treatment[Title/Abstract])) OR (root canal treatment[Title/Abstract])) AND ((((((((((((((((((((root canal filling
materials[MeSH Terms]) OR (root canal filling materials[Title/Abstract])) OR (endodontic obturation[MeSH Terms]))
OR (endodontic obturation[Title/Abstract])) OR (root canal obturation[MeSH Terms])) OR (root canal obturation[Title/
Abstract])) OR (root canal obturations[MeSH Terms])) OR (root canal obturations[Title/Abstract])) OR (Root Canal
Sealants[MeSH Terms])) OR (Root Canal Sealants[Title/Abstract])) OR (root canal cement[Title/Abstract])) OR (root
canal filling[Title/Abstract])) OR (endodontic cement[Title/Abstract])) OR (endodontic sealer[Title/Abstract])) OR (root
canal sealer[Title/Abstract])) OR (root canal cement extrusion[Title/Abstract])) OR (root canal filling extrusion[Title/
Abstract])) OR (root canal sealer extrusion[Title/Abstract])) OR (endodontic cement extrusion[Title/Abstract])) OR
(endodontic sealer extrusion[Title/Abstract]))) AND (((((((((((((((((pain[MeSH Terms]) OR (pain[Title/Abstract])) OR
(pain, postoperative[MeSH Terms])) OR (pain, postoperative[Title/Abstract])) OR (postoperative pain[MeSH Terms])) OR
(postoperative pain[Title/Abstract])) OR (hyperemia[MeSH Terms])) OR (hyperemia[Title/Abstract])) OR (toothache[MeSH
Terms])) OR (toothache[Title/Abstract])) OR (odontalgia[MeSH Terms])) OR (odontalgia[Title/Abstract])) OR (edema[Title/
Abstract])) OR (hyperesthesia[Title/Abstract])) OR (heat[Title/Abstract])) OR (swelling[Title/Abstract])) OR (touch
pain[Title/Abstract]))
Scopus
n=981
(TITLE-ABS-KEY (root AND canal AND therapy) OR TITLE-ABS-KEY (teeth, AND endodontically AND treated) OR TITLE-
ABS-KEY (endodontically-treated AND tooth) OR TITLE-ABS-KEY (root AND canal AND preparation) OR TITLE-ABS-KEY
(tooth AND root AND therapy) OR TITLE-ABS-KEY (endodontic AND therapy) OR TITLE-ABS-KEY (endodontic AND
treatment) OR TITLE-ABS-KEY (root AND canal AND treatment) AND (TITLE-ABS-KEY (root AND canal AND filling AND
materials) OR TITLE-ABS-KEY (endodontic AND obturation) OR TITLE-ABS-KEY (root AND canal AND obturation) OR
TITLE-ABS-KEY (root AND canal AND obturations) OR TITLE-ABS-KEY (root AND canal AND sealants) OR TITLE-ABS-KEY
(root AND canal AND cement) OR TITLE-ABS-KEY (root AND canal AND filling) OR TITLE-ABS-KEY (endodontic AND
cement) OR TITLE-ABS-KEY (endodontic AND sealer) OR TITLE-ABS-KEY (root AND canal AND sealer) OR TITLE-ABS-
KEY (root AND canal AND cement AND extrusion) OR TITLE-ABS-KEY (root AND canal AND filling AND extrusion) OR
TITLE-ABS-KEY (root AND canal AND sealer AND extrusion) OR TITLE-ABS-KEY (endodontic AND cement AND extrusion)
OR TITLE-ABS-KEY (endodontic AND sealer AND extrusion) AND (TITLE-ABS-KEY (pain) OR TITLE-ABS-KEY (pain,
AND postoperative) OR TITLE-ABS-KEY (postoperative AND pain) OR TITLE-ABS-KEY (hyperemia) OR TITLE-ABS-KEY
(toothache) OR TITLE-ABS-KEY (odontalgia) OR TITLE-ABS-KEY (edema) OR TITLE-ABS-KEY (hyperesthesia) OR TITLE-
ABS-KEY (heat) OR TITLE-ABS-KEY (swelling) OR TITLE-ABS-KEY (touch AND pain)
WoS
n=454
pain OR pain, postoperative OR postoperative pain OR hyperemia OR toothache OR odontalgia OR edema OR
hyperesthesia OR heat OR swelling OR touch pain
Cochrane
Reviews
n=304
root canal therapy OR teeth, endodontically treated OR endodontically-treated tooth OR root canal preparation OR tooth
root therapy OR endodontic therapy OR endodontic treatment OR root canal treatment in Title Abstract Keyword AND
root canal filling materials OR endodontic obturation OR root canal obturation OR root canal obturations OR Root Canal
Sealants OR root canal cement OR root canal filling OR endodontic cement OR endodontic sealer OR root canal sealer
OR root canal cement extrusion OR root canal filling extrusion OR root canal sealer extrusion OR endodontic cement
extrusion OR endodontic sealer extrusion in Title Abstract Keyword AND pain OR pain, postoperative OR postoperative
pain OR hyperemia OR toothache OR odontalgia OR edema OR hyperesthesia OR heat OR swelling OR touch pain in Title
Abstract Keyword - (Word variations have been searched)
Lilacs/BVS
n=4
tw:((tw:(root canal therapy OR tooth, nonvital)) AND (tw:(root canal filling materials OR root canal obturation)) AND
(tw:(acute pain OR pain, postoperative OR toothache))) AND (db:(“LILACS”))
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Moraes et al.
Influence of root canal sealer composition on postoperative pain after endodontic treatment of permanent teeth: a systematic review and meta-analyses
Moraes et al. Influence of root canal sealer composition on postoperative
pain after endodontic treatment of permanent teeth: a
systematic review and meta-analyses
indirectness, imprecision, and publication
bias [20,21]. The level of certainty among the
identied evidence can be characterized from
very low to high [21].
RESULTS
Search and Study selection
An electronic search identied 2,363 studies
by searching the databases: 463 from MEDLINE
(PubMed), 454 from Web of Science, 981 from
Scopus, 304 from Cochrane Reviews, 4 from
Lilacs (Virtual Health Library) and 157 registers
in Clinical Trials. Of these, 288 were duplicated
and removed using an automated tool. After
screening titles and abstracts, 1,931 articles were
excluded since they did not meet the inclusion
criteria. Thirty-two articles were potentially
eligible; their texts were then read in full. Three
studies were included from citation search.
Twelve studies were included in the systematic
review (Figure 1). Appendix 1 shows the studies
excluded from the full-text analysis.
Risk of bias
Nine studies had low RoB [22-30], one was
considered to have a high RoB due to bias in the
randomization process and deviations from the
intended interventions [31], while two [32,33]
were judged to be at some concerns due to bias
arising from the randomization process. Details
regarding downgrading are provided in Figure 2.
The most frequent domain causing downgrading
was bias due to the randomization process and
deviations from the intended intervention.
No study had attrition bias due to missing
outcome data or selection of reported results.
Qualitative analysis
Tables II and III present the data extractions
of the selected studies.
Of the 12 studies, two evaluated sealer
extrusion and postoperative pain [27,30], nine
sealer composition and pain [22-26], and one
evaluated both, sealer composition and extrusion
on postoperative pain [28].
Figure 1 - PRISMA flowchart of the manuscripts screened through the review process.
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Moraes et al.
Influence of root canal sealer composition on postoperative pain after endodontic treatment of permanent teeth: a systematic review and meta-analyses
Moraes et al. Influence of root canal sealer composition on postoperative
pain after endodontic treatment of permanent teeth: a
systematic review and meta-analyses
Table II - Evidence table summarizing the characteristics of the included studies
Author
Sample Endodontic treatment Pre
operative symptom
Sam
ple size Gender Tooth diagnosis Tooth type Irrigation solu-
tion Instrumentation N° sessions Obturation tech-
nique Sealers
Ambika and Satish [26]90 NI NI NI NI NI 1NI Endosequence
BC;
MTA; AH Plus
NI
Pazetal. [31] 30 NI pulpitis, pulp
necrosis, and
retreatment
NI 2.5% NaOCl ProTaper Next 1 or 2 Cold lateral
condensation
BioRoot RCS; AH
Plus
NI
Graunaiteetal. [29] 61 25 males 36
females
Asymptomatic
apical
periodontitis
Single /multi-
rooted
2% NaOCl ProTaper Gold 1Warm vertical
condensation
AH Plus; Total
Fill BC
No
Atavetal. [28] 160 67 males 89
females
Pulp necrosis and
vital teeth Single /multi-
rooted
2.5% NaOCl One Shape 1
Herofill™ Soft-
Core obturator
iRoot SP;
Innovative
BioCeramix; AH
Plus
Yes
Fonsecaetal. [27] 64 26 males
38 females
Pulp necrosis Single rooted 2.5% NaOCl Reciproc VDW 1Single cone AH Plus; Sealer
Plus BC
No
Ferreiraetal. [25] 60 19 males
41 females Pulp necrosis Single /multi-
rooted
2.5% NaOCl Wave One Gold 2
Single cone
and vertical
compaction
AH Plus; EndoFill
MTA Fillapex No
Gudlavalletietal. [33]99 45 males
54 females
Chronic
irreversible
pulpitis Multi-rooted 3% NaOCl Protaper
Universal 1 Cold lateral
condensation
Tubli-Seal EWT;
Apexit Plus; AH
Plus
Yes
Cunhaetal. [23] 69 33 males
27 females
pulpitis and pulp
necrosis Multi-rooted 2.5% NaOCl Protaper Next 2 to 4 Single cone +
accessory cones
AH Plus; Sealer
26 Yes
Tanetal. [22] 171 76 males
87 females
Pulp necrosis
and vital teeth
Single /multi-
rooted
1,25% NaOCl Rotatory files 1 or
more
Single cone and
Warm vertical
Compaction
AH Plus; TotalFill
BC Yes
Shimetal. [32] 108 36 males
31 females NI Single /multi-
rooted
2.5% NaOCl Protaper Next 2 to 4
Single cone and
Continuous wave AH Plus; Endoseal
MTA Yes
Drumondetal. [30] 330 36 males
31 females
Asymptomatic
irreversible
pulpitis
Multi-rooted 2% chlorhexidine
gel Wave One Gold 1
Single cone and
Warm vertical
Compaction
AH Plus; BC
Sealer; Bio-C
Sealer
No
Aslanetal. [24] 96 34 males
50
females
Asymptomatic
irreversible
pulpitis
Multi-rooted 5% NaOCl Reciproc VDW 1Single cone AH Plus;
Endoseal MTA;
Endosequence BC
No
NI = not informed.