CONSORT Randomized Clinical Trial
Effect of Resin-based and Bioceramic Root Canal
Sealers on Postoperative Pain: A Split-mouth
Randomized Controlled Trial
Indre Graunaite, MD, Neringa Skucaite, PhD, Greta Lodiene, PhD, Indre Agentiene, MD,
and Vita Machiulskiene, PhD
Abstract
Introduction: The aim of this study was to compare the
effect of resin-based and bioceramic root canal sealers
on the occurrence and intensity of postoperative pain
in patients with asymptomatic apical periodontitis
(AAP). Methods: Patients presenting with AAP in previ-
ously endodontically treated teeth were included in this
split-mouth blinded randomized controlled trial. For
each patient, 2 single-rooted teeth were retreated
and obturated using the warm vertical condensation
technique and different obturation materials (ie, a
gutta-percha point with resin-based sealer and a
bioceramic-coated gutta-percha point with bioceramic
sealer). Treatment of 1 root canal was performed in a
single visit. Postoperative pain was recorded by a visual
analog scale (VAS) at 24 hours, 48 hours, 72 hours, and
7 days after obturation. Results: Of the 61 included pa-
tients, 57 individuals presenting 114 teeth completed
the study. There was no statistically significant differ-
ence between the tested root canal sealers regarding
postoperative pain at any time points assessed
(P > .05). In total, 20 (35%) patients perceived pain.
Only 1 patient reported severe pain. VAS scores of 80
and 70 were reported in the AH Plus (Dentsply Maillefer,
Ballaigues, Switzerland) and Total Fill (FKG Dentaire SA,
La Chaux-de-Fonds, Switzerland) groups, respectively.
Pain intensity decreased about 2-fold in both groups
at 48 hours after treatment. There were no reports of
pain since 72 hours after obturation. The odds ratio
for pain occurrence in the lower premolars was 7.2
(95% confidence interval, 1.708–30.352) compared
with the upper front teeth. Conclusions: AH Plus and
Total Fill perform similarly in terms of the occurrence
and intensity of postoperative pain in teeth with AAP
with no material extrusion beyond the apex. (J Endod
2018;-:1–5)
From the Faculty of Odontology, Clinic of Dental and Oral Pathology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Address requests for reprints to Indre Graunaite, Faculty of Odontology, Clinic of Dental and Oral Pathology, Lithuanian University of Health Sciences, Eiveniu g 2,
LT-50009, Kaunas, Lithuania. E-mail address: indre.graunaite@lsmuni.lt
0099-2399/$ - see front matter
Copyright ª 2018 American Association of Endodontists.
https://doi.org/10.1016/j.joen.2018.02.010
JOE — Volume -, Number -, - 2018
Key Words
Calcium silicate–based sealer, epoxy resin–based sealer, postoperative pain, root canal
obturation
R eports about postoper-
ative pain in endodon-
tics range from 3%–58%
Significance
This randomized controlled trial investigated the
incidence of postoperative pain after root canal
in different studies (1).
obturation with resin-based and bioceramic root
Pain can be provoked by
canal sealers in patients with asymptomatic apical
mechanical, chemical, or
periodontitis. The results indicate that both sealers
microbiological injuries to
perform similarly in terms of postoperative pain.
periodontal tissues (2). A
number of treatment-
related parameters have been shown to be associated with the presence of postoperative
pain, including working length (WL) estimation with an apex locator connected to every
file (3), the number of visits (4), the choice of instrumentation (5), and the choice of root
canal sealer (6). Sealers placed in the root canals interfere with periodontal tissues
through the apical foramina, lateral canals, or leaching and can potentially affect the heal-
ing process in the periodontium. Thus, the local inflammation caused by root canal obtu-
ration materials may result in postoperative pain. The intensity of inflammatory reactions
depends on a number of different factors, including the composition of the sealer (7).
It has been suggested that bioceramic materials improve the outcome of endodon-
tic treatment by promoting the differentiation of odontoblasts (8) and by releasing bio-
logically active substances (9). The bioceramic materials have been shown to be less
cytotoxic compared with resin-based AH Plus (Dentsply Maillefer, Ballaigues,
Switzerland) in vitro (10). However, AH Plus (FKG Dentaire SA, La Chaux-de-Fonds,
Switzerland) exhibited stronger bonding capacity (11) and higher radiopacity (9)
compared with bioceramic sealers. The clinical significance of these characteristics
is still unclear. Data on the clinical behavior of bioceramic sealers are scarce and of
great interest.
The aim of this randomized clinical trial was to compare the potential effects of
resin-based and bioceramic sealers on the occurrence and intensity of postoperative
pain in patients with asymptomatic apical periodontitis (AAP).
Materials and Methods
The protocol of the trial was approved by the local research ethics committee (no.
BE-2-23).
Resin-based and Bioceramic Root Canal Sealers 1
CONSORT Randomized Clinical Trial
Patient Selection
The study was performed using a split-mouth design. Patients
requiring root canal retreatment of at least 2 single-rooted teeth diag-
nosed with AAP because of radiographically detected periapical lesions
were included. Diagnosis was confirmed based on the clinical examina-
tion and periapical x-rays. Only teeth presenting with no clinical symp-
toms and with a periapical score from 2 to 4 according to Orstavik et al
(12) were included. Cases with a widened periapical periodontal space
and inadequate root canal filling corresponded to a score of 2. Teeth
with large periapical lesions (score 5) were excluded to minimize
the chances of exacerbation of the local inflammatory process.
The patients were selected from those referred to the Hospital of
Lithuanian University of Health Sciences, Kaunas, Lithuania, for end-
odontic therapy over a 9-month period extending from January to
September 2017. All patients who met the inclusion criteria were invited
to participate in the study. The inclusion/exclusion criteria are listed in
Table 1. All patients received oral and written information about the
study and signed an informed consent form.
A pilot study with 13 patients was performed in order to determine
the sample size. The protocol of the pilot study was the same as that of
the main study. The sample size was calculated based on a type I error of
0.05 and a power of 80%. The least mean difference between the groups
was considered 1. The standard deviation obtained from the pilot study
was 2.5. Thus, the calculated sample size was 50 patients. Assuming
possible loss to follow-up, 61 patients were included in the study.
Treatment Protocol
The treatment was performed at the Clinic of Dental and Oral Pa-
thology, Hospital of Lithuanian University of Health Sciences by 2
experienced endodontists. Each root canal was retreated in 1 visit
in order to minimize the number of procedures and the potential ef-
fect of intracanal medication. Treatment of the second root canal was
scheduled no earlier than 1 week after the first treatment session. No
local anesthesia was applied during the treatment. The entire proced-
ure was performed under an operating microscope (OPMI Pico; Carl
Zeiss, Gottingen, Germany) and rubber dam (Hygenic, Akron, OH)
isolation. An old root canal filling material was removed with Pro-
Taper Universal retreatment files (Dentsply Maillefer) and/or using
Sonofile K-file tips #25 (Satelec Acteon, Merignac Cedex, France)
mounted in a P5 Booster ultrasonic scaler (Satelec Acteon) device.
No chemical solvent was used. The WL was established by #10 or
larger K-files (Dentsply Maillefer) and a Root ZX II apex locator (J
Morita, Kyoto, Japan) and confirmed on the x-ray. A glide path was
created using Pathfiles (Dentsply Maillefer). The root canals were
shaped using the ProTaper Gold system (Dentsply Maillefer). All ro-
tary files were driven by an X-Smart endodontic motor (Dentsply Mail-
lefer). The WL was verified by the apex locator after each instrument to
avoid overinstrumentation. The canals were irrigated with 2 mL 2%
sodium hypochlorite (NaOCl) (Cerkamed, Stalowa Wola, Poland) us-
ing Appli-Vac 27-G tips (Inter-Med, Racine, WI) after each file. The
size of the master apical file varied from F2 to F5 according to the
size of the apical foramen. Final irrigation was performed with ultra-
sonic activation for 30 seconds with each solution (ie, 2.0 mL NaOCl,
2.0 mL 17% EDTA [Cerkamed], and 2.0 mL NaOCl per canal).
Root Canal Obturation
For every patient, the root canal of 1 tooth was obturated with an
epoxy resin–based sealer (AH Plus) and a gutta-percha point (Dentsply
Maillefer). The root canal of another tooth was obturated with bio-
ceramic Total Fill sealer and a Total Fill BC point (FKG Dentaire SA).
The choice of the material was randomly made by the dental assistant
using a coin toss. The patient was blinded to treatment allocation. Blind-
ing of the operator was impossible because of the different appearances
of the obturation materials.
The root canal sealer was prepared according to the manufac-
turer’s instructions. After drying with paper points, a small amount of
the sealer was introduced into the canal with a paper point. A gutta-
percha point was adapted, and the canal was obturated by a warm ver-
tical condensation technique using the Calamus Dual System (Dentsply
Maillefer) in both groups. The depth of the plugger was minus 5 mm
from the WL. The temperature of the heated plugger was 180
C and
150
C for the AH Plus and Total Fill groups, respectively, as recommen-
ded by the manufacturers. The coronal cavity was sealed with Interme-
diate Restorative Material (Dentsply Maillefer).
Assessment of Postoperative Pain
The primary study outcome was postoperative pain. Every patient
received a visual analog scale (VAS) to record pain intensity at 24 hours,
48 hours, 72 hours, and 7 days after treatment. The VAS consisted of a
100-mm-long line divided into 10 equal intervals from 0 (no pain) to
100 (very severe pain). Every patient was asked to mark his or her
perceived postoperative pain level on the line. The distance between
‘‘no pain’’ and the mark defined the subject’s pain (13). The patients
were contacted at 4 consecutive time points, and the recorded pain
scores were collected. VAS was not applied for preoperative pain assess-
ment, assuming that the absence of any clinical symptoms before end-
odontic retreatment would correspond to a score of 0. The patients
were asked to report whether they had taken analgesic medication after
treatment.

TABLE 1. Inclusion/Exclusion Criteria of the Study Participants

Inclusion criteria Exclusion criteria
Patients requiring root canal retreatment of at least Medically compromised patients (with immunosuppressive/systemic
2 teeth diseases, patients on medications)
Both teeth are single rooted with a single (type I Patients who refuse to participate
according to Weine) canal
Both teeth are diagnosed with asymptomatic apical Symptomatic teeth
periodontitis
The periapical index score is from 2 to 4 according to Inability to reach the full working length
Orstavik et al (12)
Teeth are asymptomatic Periodontologically compromised teeth (probing depth >4 mm)
Complications during treatment (separation of a file, ledging, and so on)
Overfilling (filling beyond the radiographic apex) or short filling (>2 mm
from the radiographic apex)

2 Graunaite et al. JOE — Volume -, Number -, - 2018

 CONSORT Randomized Clinical Trial
Statistical Analysis TABLE 2. The Frequency of Different Types of Teeth in Relation to Treatment
Statistical analysis of the data was performed using software Mode
packages for storage and analysis of data SPSS 22.0 (IBM Corp, Ar- AH Plus, Total Fill,
monk, NY). All parametric data were expressed as the Group of teeth n (%) (n = 57) n (%) (n = 57)
mean  standard deviation. For the comparison of VAS scores, the Maxillary front teeth 21 (36.8) 18 (31.6)
Wilcoxon nonparametric test was used. For the frequency of tooth Maxillary premolars 10 (17.5) 16 (28.1)
types among the tested materials and the distribution of the patients Mandibular front teeth 15 (26.3) 10 (17.5)
among VAS scores, the chi-square test was performed. For the asso- Mandibular premolars 11 (19.3) 13 (22.8)
ciation of pain with a tooth type, odds ratios were calculated using bi- c23 ¼ 3:134, P > .05.
nary logistic regression analysis. A P value < .05 or less was
considered significant.
tients and only those with postoperative pain (Table 4). The odds
ratio (95% confidence interval) for the lower premolars compared
Results with the upper front teeth was 7.2 (95% confidence interval,
Over a 9-month period, 1284 patients were screened for eligibility 1.708–30.352), indicating a significantly higher likelihood of
(Fig. 1). The screening was completed when a sufficient sample of pa- pain occurrence in the lower premolars. The distribution of VAS
tients had been collected. Of all the invited patients, 16 were excluded scores among the groups of teeth after 24 hours and 48 hours
following the defined exclusion criteria; 2 patients were diagnosed with is presented in Figure 2A and B, respectively.
diabetes mellitus, 1 root canal could not be negotiated, 1 canal ex-
hibited exudation, and 12 patients refused to take part in the study. Discussion
No cases exhibited radiographically visible sealer extrusion. Thus, a to- Postoperative pain in endodontics reflects activation of the local
tal of 122 teeth from 61 patients (25 men and 36 women) were available inflammatory response in the periapical tissues (14), which is known
for further analysis. The mean age of the patients was 49.5  12.82 to be associated with the release of biochemical mediators such as reac-
years. tive oxygen species (ROS) (15). Oxidative stress and, more specifically,
The follow-up period was 7 days. Four participants did not ROS have been shown to be linked with inflammatory pain in vivo (16,
respond during the follow-up and thus were excluded from the study. 17). The production of ROS increased 4 to 7 times when the human
The responses from 57 patients were evaluated after 1 week. The fre- pulp cells had been treated with the root canal sealers in vitro (18).
quency of the different types of teeth in relation to the treatment Resin-based AH Plus was slightly cytotoxic (10) and released toxic
mode (ie, sealer used for obturation) is summarized in Table 2. monomers, such as bisphenol A diglicidyl ether (19). The bioceramic
In total, 20 (35%) patients perceived pain of varying intensity. Only sealer Total Fill (also known as EndoSequence BC [Brasseler USA,
1 patient reported severe pain. The VAS scores recorded were 80 and 70 Savannah, GA] or iRoot SP [Innovative BioCeramics, Vancouver, Can-
in the AH Plus and Total Fill groups, respectively. None of the study par- ada]) exhibited a cytotoxic effect as well although it was significantly
ticipants reported any pain since 72 hours after obturation. The distri- lower compared with AH Plus (10). The observed cytotoxicity of the
bution of the patients with respect to the pain scores and the tested sealers implied that their contact with the periapical tissues could pro-
materials at 2 time points (24 hours and 48 hours) is presented in voke postoperative pain. Moreover, the occurrence of the clinical symp-
Table 3. Two patients reported an intake of nonsteroid analgesics at toms was associated with the composition of the sealer in cases of gross
the 24-hour time point. An intake of analgesic medication was associ- overfills (20). It was shown that the extrusion of AH Plus delayed peri-
ated with a VAS score higher than 30. apical healing (21). However, in cases of slight extrusion, the treatment
There was no statistically significant difference between the outcome was not significantly affected by the type of sealer (22), and no
mean values of the VAS scores for the AH Plus and Total Fill groups correlation between sealer extrusion and postoperative pain was
at any of the time points assessed when analyzing all included pa- observed (23).
It is difficult to attribute the pain incidence to any specific factor in
clinical research because endodontic treatment comprises a complex of
Assessed for eligibility Excluded n = 1223 procedures including chemomechanical debridement and obturation.
n = 1284 Even though the retreatment of teeth with AAP was shown to cause fewer
Did not meet inclusion
criteria n = 1207
TABLE 3. The Distribution of Patients with Respect to the Pain Scores and the
Due to exclusion criteria Tested Materials at 2 Time Points (after 24 Hours and after 48 Hours)
Randomized n = 16
n = 61 After 24 h After 48 h
AH Plus, Total Fill, AH Plus, Total Fill,
VAS scale n (%) n (%) n (%) n (%)
score (n = 57) (n = 57) (n = 57) (n = 57)
Lost to follow-up
n=4 0 45 (78.9) 47 (82.5) 48 (84.2) 50 (87.7)
10 6 (10.5) 8 (14.0) 6 (10.5) 6 (10.5)
20 4 (7.0) 2 (3.5) 1 (1.8)
30 1 (1.8)
40 1 (1.6) 1 (1.8)
Analysed 70 1 (1.8)
n = 57 80 1 (1.6)
c26 = 8.329, P > .05 c26 = 1.374, P > .05
Figure 1. A flowchart of the study. VAS, visual analog scale.

JOE — Volume -, Number -, - 2018 Resin-based and Bioceramic Root Canal Sealers 3
CONSORT Randomized Clinical Trial
TABLE 4. Descriptive Statistics and Distribution of the Mean Values of Postoperative Pain Scores among All Patients and among Only Those with Postoperative Pain
after 24 Hours and 48 Hours
Time Root canal sealer n Mean VAS score (95% CI) SD Minimum Maximum
After 24 h AH Plus 57 4.56 (1.20–7.93) 12.69 0 80
12* 21.67 (8.72–34.61) 20.38 10 80
Total Fill 57 3.16 (0.40–5.91) 10.38 0 70
10* 18.00 (4.18–31.82) 19.32 10 70
After 48 h AH Plus 57 2.46 (0.63–4.28) 6.89 0 40
9* 15.56 (7.76–23.35) 10.14 10 40
Total Fill 57 1.40 (0.35–2.46) 3.98 0 20
7* 11.43 (7.93–14.92) 3.78 10 20
CI, confidence interval; SD, standard deviation; VAS, visual analog scale.
*Data of patients with postoperative pain.

symptoms than in vital noninfected cases (24), pain could still be pro-
voked by infection. When designing the present study, considerable
attention was paid to control factors that could potentially provoke post-
operative pain. First of all, the presence of preoperative pain is known to
be a strong predictor of postoperative pain (25, 26). Therefore, only
symptom-free patients were invited to this study. Furthermore, by using
a split-mouth design, the potential effect of individual differences, such
as patient’s age and sex was minimized (23, 27). Only single-rooted
teeth with a single canal were included to facilitate WL control and to
avoid overinstrumentation (3). The canals were shaped with contin-
uous motion rotary instruments that are known to cause less postoper-
ative pain in patients (5). Postoperative pain was previously shown to be
significantly lower in teeth with periapical radiolucency (27); therefore,
for the present study, only patients diagnosed with AAP were selected.
Because single-visit endodontic therapy had performed similarly to
2-visit treatment in terms of postoperative pain (4) and healing of peri-
apical tissues (28), it was used in this study to minimize the number of
procedures and variations of intracanal medication used. VAS is a vali-
dated method for measuring postoperative pain in dental research (25,
27). However, because such an assessment is very subjective, VAS is of
most value when identifying changes within individuals rather than
comparing across a group of individuals (29). The split-mouth design
enabled the measurement of differences in pain intensity within individ-
uals.
Pain after endodontic treatment had been shown to be particularly
related with multirooted teeth (25); therefore, only premolars and front
teeth were included in this study. Based on the present results, the lower
premolars had a significantly higher chance to develop postoperative
pain compared with the front teeth. This could possibly be attributed
to the variations in root canal morphology (30) and to inaccessible
auxiliary canals. Because the obturation materials used in the study
were similarly distributed with respect to the tooth type (Table 2), it
is likely that the tooth type did not influence the comparison of the effect
with regard to postoperative pain.
Postoperative pain was measured at 4 time points: 24 hours,
48 hours, 72 hours, and 7 days. These time points were previously
used when evaluating pain of endodontic origin (26) and used in
in vitro cytotoxicity tests (31, 32). Although the in vitro studies
estimated the differences in cytotoxicity between AH Plus and Total
Fill (10), such differences did not seem to reflect clinically. In this trial,
no statistically significant difference in pain occurrence between the
root canals obturated with different sealers was observed at any of
the assessed time points. Similarly, no difference regarding postopera-
tive pain was detected in the study in which resin-, zinc oxide eugenol-,
and MTA-based root canal sealers had been tested (6) although a num-
ber of confounding factors, such as small sample size, large intervals
between the time points, and individual differences among the patients,
could have influenced the results. The low mean VAS score (<10) ob-
tained in the present study was in agreement with the results of Thakur
et al (6). However, they detected pain in all study groups even 6 months
after obturation. Possibly, the persisting microbial infection could be
responsible for such a long-lasting presence of symptoms. In contrast,
no pain since 72 hours after obturation was reported in the current
study.

A 36
B 36 upper front teeth
upper front teeth
34 upper premolars 34 upper premolars
lower front teeth lower front teeth
32 32
lower premolars lower premolars
30 30
28 28
26 26
24 24
22 22
20 20
Count
Count

18 18
16 16
14 14
12 12
10 10
8 8
6 6
4 4
2 2
0 0
0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60 70 80
VAS scale, % VAS scale, %

χ2=27.803, df=18, p≤0.05 χ2=18.481, df=9, p≤0.05

Figure 2. The distribution of VAS scores among groups of teeth after (A) 24 hours and (B) 48 hours.

4 Graunaite et al. JOE — Volume -, Number -, - 2018


Despite the thorough control of the potential causative factors of
pain, it was still recorded in this study. The highest VAS score was re-
ported at 24 hours after obturation and decreased with time. One could
speculate that cytotoxic unpolymerized root canal sealers (33) known
to induce ROS formation before material setting (31) and their leaching
components (19) could have played a role during the first 24 hours.
Most of the study patients with postoperative pain indicated a score
of 20 or lower on the VAS scale. The recorded pain prevalence
(35%) was similar to the estimates reported in the systematic review
by Pak and White (34). However, the intensity of pain after 24 hours
was lower than in the other studies (34). This could be attributed to
the elimination of many pain-inducing factors as described earlier.
Two patients with the highest VAS scores (30–40 and 70–80) reported
an intake of analgesics during the first 24 hours after obturation with
either material. A low intake of analgesics had been reported in another
clinical study of retreatment cases as well (26), whereas a higher intake
of analgesics had been observed in symptomatic cases (35). Further-
more, low postoperative pain scores recorded in the present study
could potentially be explained by the absence of overfills, indicating a
small contact area between the filling material and the periapical tissues.
Further studies are needed to investigate the effect of canal obturation
materials in the overfilled cases.
In conclusion, postoperative pain in the teeth diagnosed with AAP
and obturated with resin-based or bioceramic root canal sealers with
no extrusion beyond the apex was generally low, affecting 35% of the
study participants. The sealers performed similarly in terms of occur-
rence and intensity of postoperative pain when the other treatment-
related irritants were minimized.
Acknowledgments
The authors deny any conflicts of interest related to this study.
Supplementary Material
Supplementary material associated with this article can be
found in the online version at www.jendodon.com (https://doi.
org/10.1016/j.joen.2018.02.010).
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