Evaluation of the Effect of the Intensity and Occurrence of Postoperative Pain of Resin-Based and Bioceramic Root Canal Sealers: A Systematic Review and Meta-Analysis of Randomized Controlled Trial Studies

Objective: To evaluate resinand bioceramic root canal sealers affect postoperative intensity and pain occurrence. Material and Methods: From the electronic databases, PubMed, Cochrane Library, Embase, ISI have been used to perform systematic literature until September 2020. Electronic titles were managed using the Endnote X8 software. They performed searches with mesh terms. Two reviewers blindly and independently extracted data from studies that included data for data extraction. Results: A total of 186 potentially relevant titles and abstracts were found. Finally, four studies were included. Pain score was (RR = -0.20; 95% CI -1.09–0.68; p= 0.65). This result showed no statistically significant difference for the resinbased and bioceramic root canal sealers after 24 hours between the VAS scores. Conclusion: Postoperative pain was low in Patients requiring root canal retreatment and obturated with resin-based or bioceramicbased sealers without extrusion beyond the apex. No differences were observed between postoperative pain in resin-based and bioceramic root canal sealers 24 and 48 hours postoperatively.


Introduction
Studies have shown that endodontic postoperative pain between 3 to 58 % [1][2][3]. Pain may occur in periodontal tissues after mechanical, chemical, and microbiological injuries [4]. There are various parameters in treatment that can cause postoperative pain. One of these parameters is including working length (WL).
Also, the number of visits, selection of instruments, and the selection of root canal sealers are other related parameters [5][6][7].
Sealers placed in the root canals and interact with the periodontal tissues through the apical perforation, lateral canals, or leaching can affect the periodontium's healing process. As a result, postoperative pain is caused by local inflammation of the root canal [8].
Bioceramic materials can help endodontic treatment by releasing biologically active substances and promoting odontoblasts' differentiation [9][10][11][12]. In vitro studies have shown that bioceramic materials were less cytotoxic than resin-based materials [13][14][15][16]. Other studies have also shown that resin-based have stronger bonding capacity and higher radiopacity than bioceramic materials [17,18]. Graunaite et al. [19], in a split-mouth randomized controlled trial, showed resin-based sealer (AH Plus) and Total Fill had a similar occurrence and intensity of postoperative pain.
Given that the exact results are not noticeable, and a systematic review and meta-analysis studies have not been performed in this field, the researcher decided to review the results of RCT studies; the aim of this study is to evaluate the effect of resin-based and bioceramic root canal sealers on postoperative pain intensity and occurrence.

Search Strategy
From the electronic databases, PubMed, Cochrane Library, Embase, ISI have been used to perform systematic literature over the last five years between 2015 to September 2020. Endnote X8 software was used to manage electronic titles. Searches were performed using mesh terms: This study is based on the Systematic Review and Meta-Analysis (PRISMA) Statement-Preferred Reporting Items [20] and the PICO or PECO Strategy (Table1). The following inclusion criteria were adopted: 1) Randomized controlled trial studies, controlled clinical trials, and prospective and retrospective cohort studies; 2) Used AH Plus; 3) Used bioceramic root canal sealers; 4) Patients requiring root canal retreatment; 5) VAS scale; and 6) In English.
Regarding the exclusion criteria, the following were established: 1) Periapical lesions; 2) Studies carried out in vitro, case reports, case studies, and reviews; and 3) Animal studies.

Data Extraction and Method of Analysis
The data were extracted from the research that included information about the study, years, study design, sample size, mean/ range of age, number of teeth, scale, root canal sealers, and follow-up period. The quality of the included studies has been evaluated using the tool of Cochrane Collaboration [21]. The scale scores for low risk were 1 and for High and unclear risk was 0. Scale scores range from 0 to 6. A higher score means higher quality. Two reviewers blinded and extracted data independently for data extraction of studies that included.
Moreover, the risk ratio between two groups (resin-based and bioceramic root canal sealers), the model for random effect and the method for restricted maximum likelihood (REML) were calculated with a 95% confidence interval (CI). Random effects were used to resolve the potential heterogeneity, and I 2 showed heterogeneity. Stata Statistical Software, V.16 (StataCorp LLC., TX, USA) was used in meta-analysis.

Results
According to the research design, 186 potentially important research abstracts and titles have been discovered in our electronic searches. In the first phase of the study selection, 156 research has been about the topics and abstracts. Therefore, we thoroughly assessed the complete full-text papers of the rest 28 studies in the second stage to exclude 24 publications due to the lack of the defined inclusion criteria. Then, four papers remained in agreement with our inclusion criteria required (Figure 1).

Sample Size
Therefore, four studies (randomized controlled trials) have been included. The number of patients a total was 121. The mean age was 42.6 years. The number of teeth a total was 276. Per patient received a visual analog scale (VAS) in all studies to record pain intensity 24 hours, 48 hours, 72 hours, and seven days after treatment ( Table 2).

Bias Assessment
According to Cochrane Collaboration's tool, two studies had a total score of 4/6, one study had a total score of 5/6, and one study had a total score of 6/6. This result showed a low bias risk in all studies and high quality ( Table 3).  (Figure 2).   (Figure 3).

Pain Scores after Seven Days
No pain or mild pain was reported in the studies after seven days.

Compared to Pain Scores after 24 and 48 Hours
Postoperative pain was felt more in the first 24 hours than after 48 hours, and the VAS score was higher after 24 hours vs. 48 hours.

Discussion
The local inflammatory response in periapical tissues causes postoperative pain in endodontics treatment [25,26]. In vivo studies have reported that reactive oxygen species can be directly associated with inflammatory pain [27]. If human pulp cells were treated in vitro with the root canal sealers, reactive oxygen species would increase from 4 to 7 times [28,29].
Resin-based AH Plus can also release toxic monomers such as diglicidyl ether bisphenol A, and the bioceramic sealer can have cytotoxic effects. But it should be noted that iRoot SP is less toxic than AH Plus [30,31]. Postoperative pain is triggered when the sealers' cytotoxicity implied contact with the periapical tissue. In gross overfilling cases, it can also be caused by the sealer [32,33].
No statistically significant difference in the present systematic review results and meta-analysis is shown in the postoperative pain observed at any of the points in time between the root canals obturated with resin-based and bioceramic sealers. It took 24 hours, 48 hours, 72 hours, and seven days to measure pain by 4 points. These time points have been used in studies to assess postoperative pain, as well as in vitro cytotoxicity tests [33].

Conclusion
Postoperative pain was low in patients requiring root canal retreatment and obturated with resinbased or bioceramic-based sealers without extrusion beyond the apex. No differences were observed 24 and 48 hours postoperatively between postoperative pain in resin-based and bioceramic root canal sealers. This means that resin-based and bioceramic root canal sealers act the same in incidence and postoperative pain severity. It will also require randomized controlled trial studies comparing resin-based and bioceramic root canal sealers with high sample sizes and seven days.