The Incidence and Intensity of Postoperative Pain and Flare-up Following the Use of Three Different Intracanal Medicaments In Teeth With Posttreatment Apical Periodontitis: A Randomized Clinical Trial

The Incidence and Intensity of Postoperative Pain and Flare-up Following the Use of Three Different Intracanal Medicaments In Teeth With Posttreatment Apical Periodontitis: A Randomized Clinical Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Incidence and Intensity of Postoperative Pain and Flare-up Following the Use of Three Different Intracanal Medicaments In Teeth With Posttreatment Apical Periodontitis: A Randomized Clinical Trial Adile Esen Angın, Hicran Dönmez Özkan, İlkim Pınar Saral, Berdan Aydın This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4090764/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Jun, 2024 Read the published version in Clinical Oral Investigations → Version 1 posted 8 You are reading this latest preprint version Abstract Objectives This randomized clinical trial aimed to compare the effect of intracanal medicaments on the incidence of postoperative pain and flare-up with posttreatment apical periodontitis (PTAP) of retreatment cases. Materials and Methods One hundred-twenty patients diagnosed with PTAP with single-rooted teeth with single-canal without spontaneous pain or swellings were included and randomly divided into three groups according to the intracanal medicament used. Intracanal medicaments were placed into the root canals following the removal of previous root canal fillings and re-instrumentation. Calcium hydroxide (Ca (OH) 2 ), chlorhexidine gel (CHX), calcium hydroxide and chlorhexidine gel combinations were used as intracanal medicaments. Postoperative pain scores were recorded at 6 and 12 hours and at 1, 2, 3, 4, 5, 6, and 7 days using visual analog scale (VAS). Sensitivity on percussion, spontaneous pain, swelling, antibiotic and analgesic requirements of the patients were evaluated during clinical examinations performed postoperatively after 2 and 7 days. Results There were no statistically significant differences between groups in terms of VAS scores following the intracanal medicament application (p > 0.05). However, compared to the patients belong to 20–34 and 50–65 age groups, greater VAS scores was observed in patients between the ages of 35–49 at 12 hour, and 3, 4, 7 days (p < 0.05). Flare-up was observed in only one patient in CHX gel group, and no flare-up was observed in other groups. Conclusions Similar postoperative pain incidence in all experimental groups indicates that all three medicaments are clinically acceptable in inter-appointment management of retreatment cases in terms of post endodontic pain and flare-up. Clinical Relevance: In this randomized clinical trial, three different intracanal medicaments were utilized in nonsurgical endodontic retreatment and their effect on the postoperative pain and flare-up incidance was examined. There are limited number of prospective clinical trials in the literature about this issue. Thus, this study will be significant contribute to the literature. calcium hydroxide chlorhexidine gel endodontic postoperative pain flare-up intracanal medicament Figures Figure 1 Figure 2 INTRODUCTION Postoperative pain and flare-up are among clinical complications encountered during and after endodontic treatment ( 1 , 2 ). Although endodontic treatment done using contemporary techniques provides appropriate biological results, preventing pain during and after the treatment is as much desired ( 3 ). Postoperative pain occurs as a result of many factors such as presence of pain preoperatively and procedural variations. Factors such as gender and age, presence of a systemic disease, condition of the pulp, presence of preoperative pain, number of appointments, use of intra-canal medications and localization of the tooth in the arch may stimulate postoperative pain and flare-up ( 4 ). Many studies were reported that the frequency of flare-up is higher in retreatment cases compared to the flare-up rate of patients with primary root canal treatment ( 4 – 7 ). One of the most important causes of postoperative pain is microorganisms that cannot be eliminated from the root canal. Microbial flora in cases with unsuccessful endodontic treatment history is different from that of primary root canal infections. Enterococcus faecalis constitutes a small part of the flora in cases where root canal treatment is performed for the first time, while plays a major role in the etiology of persistent periradicular infections with root canal treatment ( 8 ). Therefore, in retreatment procedures; although microbial eradication is mainly achieved by the chemomechanical preparation, root canal medicaments may help in disinfection of the root canal ( 9 , 10 ). Calcium hydroxide is the most used canal dressing in endodontic practice since the early 1930s ( 11 ). Although it is the most preferred medication, it does not show an equal effect against all the bacterial species in the root canal system ( 12 , 13 ). Chlorhexidine, which has been widely used in dentistry since the 1970s, was recommended in irrigation and as an intra-canal disinfectant in endodontics. In a study, its solutions, gels, and controlled release preparations were found effective against resistant microorganisms such as Enterococcus faecalis and Candida albicans ( 14 ). Owing to its viscosity, chlorhexidine gel was found better in mechanical cleaning compared to its liquid counterpart ( 15 ). A study reported that when used as an intra-canal disinfectant, chlorhexidine is more effective than calcium hydroxide against E. faecalis ( 16 ). However, chlorhexidine alone can not form a physical barrier and cannot provide radiopacity ( 12 ); thus, its use combined with calcium hydroxide may offer such features. Synergistic effect of chlorhexidine and calcium hydroxide mixture increase antimicrobial activity of calcium hydroxide while preserving its barrier function ( 12 , 17 – 19 ). There is limited knowledge about the effectiveness of this combination on postoperative pain and flare-up incidence in retreatment cases. Therefore, the aim of this study is to the evaluate the effect of chlorhexidine, calcium hydroxide and chlorhexidine and calcium hydroxide mixture as intra-canal medicaments on postoperative pain and flare-up incidence and on the frequency of analgesic use in teeth with PTAP. The null hypothesis tested in this study is that the type of intra-canal medicaments used would not affect the incidence and the intensity of post-treatment endodontic pain and flare-up incidence. MATERIALS AND METHODS The research protocol was recorded in www.ClinicalTrials.gov database (National Library of Medicine 8600 Rockville Pike, Bethesda, MD 20894, United States) under ID NCT05052814 and the study was approved by our university’s Clinical Research Ethics Committee (Protocol ADUDHF2019/063) and Pharmaceuticals and Medical Devices Agency of our country (Protocol 2019/ 079). The minimal estimated sample size for each group was computed as 34 based on a previous research data ( 20 ) (alpha-type error of 0.05, a beta power of 0.95 was specified by G*power V.3.1.9.2 software (Heinrich Heine, University of Düsseldorf, Düsseldorf, Germany). To increase the stastical power and considering the potential patient dropouts, 40 patients per group were enrolled. Thus, a total of 114 patients were included in this study. Patient Selection and Eligibility Criteria The patients were selected from those referred to the Hospital of Aydın Adnan Menderes University of Dental Faculty from March 2019 to August 2020. All patients meeting the inclusion criteria were invited to the participate in the study. One hundred-twenty systematically healthy patients aged between 20 to 65 years met the criteria and agreed to participate in the study. Patients who had root canal treated single-rooted incisior or mandibular premolar teeth with a single root canal at least or equal three years ago but still had PTAP were included in this study. Failure of the previous root canal treatment was determeined by clinical and radiographic examinations. Teeth with clinal signs and semptoms for the requirement of retreatment except cases with preoperative swelling, spontaneous pain, severe percussion and palpation were included in this study. All inclusion and exclusion criteria are listed in Table 1 . All participants were first informed about study design and clinical treatment procedures with risks and signed a written informed consent form. Table 1 . Inclusion/exclusion criteria of the participants INCLUSION CRITERIA EXCLUSION CRITERIA Patients between 20 - 65 years of ages Pregnant patients and patients in lactation period Patients who agree to participate this study Having used corticosteroids in the last 6 months Patients had not used analgesic or antibiotics in last 7 days Individuals with systemic diseases (endocarditis, immune system diseases,etc.) requiring antibiotic prophylaxis Single root and single-canal incisor, canine, premolar teeth that have been endodontically treated only once Having received immunosuppressive therapy within the last week Asymptomatic teeth with previous endodontic treatment but with abscess experience or pain on chewing/percussion history developed within last 12 months. Patients who had systemic or allergic sensitivty for the NSAIDs and local ananesthetics Teeth, although asymtomatic, but with newly developed periapical radiolucency within two years compared to the radiographic findings present 2 years ago at the time of root canal tretament was done. The presence of advanced periodontal disease (probing depth > 4 mm) Teeth with periapical radiolucency, but with increased or unchanged according to pre-treatment radiography The presence of a foreign body in the root canal that prevents entry (broken file, post, etc.) Patients with good oral hygiene Fracture or crack in the root Teeth that cannot reach the working length due to calcification in the root canal and step formation Teeth that cannot be restored due to excessive loss of material in the coronal structure The presence of more than one adjacent tooth requiring endodontic treatment that may cause reflected pain in the same patient. Teeth that develop any complications ( breakage of endodontic file, perforation, inability to determine the working length with the apex finder) during the removal of the canal filling material. Table 2. Distribution of the types of the teeth from the medicament’s groups. Random Sequence Generation and Allocation Concealment The volunteers were randomly assigned to three different medicament groups. The allocation was performed according to Consolidated Standards of Reporting Trials 2010. Stratified randomization was performed for each group according to gender and age. After patients were divided based on gender and age-groups, they were randomly placed in the medicament groups to make an equal distribution of the type of medicament used. To implement a random placement of patients, different blocks were designed with the combination of covariates; and a simple randomization procedure, envelope selection, was applied within each block to assign participants to one of the blocks. Treatment Protocol All root canal treatments were performed by the same clinician. During diagnostic examination, periapical radiographs were obtained using a phosphor plate (Vistascan Mini Easy, Dürr Dental) and using the long-cone paralleling technique under standard exposure conditions and recorded. After the clinical and radiographic evaluations of relevant teeth; the findings including spontaneous pain, swelling, fistula, restoration type and condition, caries, fractures were recorded on the case report forms. Tests such as percussion, palpation, mobility and periodontal probing were performed to determine the presence of preoperative pain. All patients were received 2-visit root canal retreatments. After administration of local anaesthesia (2 mL, 4% articaine hydrochloride containing 1:100 000 adrenalin), a rubber dam was applied for the isolation. No additional local anesthesia was given since patient comfort was provided with delivered amount. Following the preparation of the access cavity, ProTaper Universal Retreatment files (Dentsply Maillefer, Ballaigues, Switzerland) were used at 500 rpm and 3 Ncm torque to remove the root canal filling. D1 file (30 / .09) was used in the coronal third, D2 file (25 / .08) in the middle third, and D3 file (20 / .07) in the apical third region. Working length was determined to be 1 mm shorter than the value (0.0) indicated by the electronic apex locator (Raypex 6, VDW, Munich, Germany) and confirmed radiographically. Apical patency was established with a size 10 K-file. Next, shaping procedure was completed at the working length using ProTaper Next rotary files: X1, X2 and X3 (Dentsply Maillefer, Ballaigues, Switzerland), respectively. In large canals where the use of X3 files result in under-instrumentation of apex, shaping was completed with X4 and X5 files. No chemical solvent was used to remove the previous root canal fillings. A 27-gauge notched type irrigation needle (Endo Eze; Ultradent Products Inc. South Jordan, USA) was placed loosly 2 mm shorter of working length while performing 2 mL, 5.25% NaOCl irrigation between each file. After the last used file, shaping for retreatment was considered complete when there is no residual canal filling observed under 2.5x magnification and the irrigation solution is clear from debris. Then, a periapical radiograph was taken to verify complete removal of the filing materials. If any remaning material is visible on the radiograph, shaping was completed with X4 and X5 files and a size # 50 Hedström file was used until a complete removal of previous filling is achieved. After that, final irrigation was done under activation (Endoactivator, Dentsply, Tulsa, USA) using 2 mL of 17% EDTA followed by 4 mL of 5.25% NaOCl. Endoactivator was run for 20 seconds between 1 mL 5.25% NaOCl irrigation. Root canal was rinsed with sterile distilled water and dried with sterile paper-points. Finally, medicaments were placed with a lentulo spiral (Dentsply Maillefer, Switzerland) as follows: Group 1 Calcium hydroxide paste (Ultracal XS; Ultradent South Jordan, USA) Group 2 2% Chlorhexidine gel (Gluko-Chex, Cerkamed, Stalowa Wola, Poland) Group 3 Equal amounts of calcium hydroxide (Ultracal XS; Ultradent South Jordan, USA) and chlorhexidine gel (Gluco-Chex, Cerkamed, Stalowa Wola, Poland) were mixed and placed. After the visual observation of the canals filled with medicament, sterile teflon tape was placed in the canal orifice and the access cavity was sealed with glass ionomer cement (Kavitan ™ Plus; Pentron, SpofaDental, Czech Republic). Postoperative Pain Evaluation Postoperative pain levels were evaluated for seven days using a VAS scale. Post operative pain scores were recorded at 6, 12 hours and at 1, 2, 3, 4, 5, 6 and 7 days after the medicaments were placed. In the VAS scale given to the patient two opposite limits of the parameter are marked on both ends of a line prepared as 0-100 mm. According to the scale, while 'no pain' is marked with zero, 'unbearable pain' is marked with 100 on the line ( 21 ). The patients were asked to evaluate own pain status by marking the line on the specified days and times. Patients who could not communicate to submit the evaluation forms were excluded from the study. The patients were prescribed 400 mg ibuprofen (Brufen, Abbott, IL, USA) and instructed to use only for severe pain. Frequency and time of use of analgesics were recorded. In addition to the documentation, oral examinations were performed on the 48th hour and at 7 days. Sensitivity on percussion, spontaneous pain, swelling of surrounding tissues and antibiotic requirement were also examined and recorded. Evaluation of Previous Root Canal Filling Level Evaluation of the status of primary root canal fillings was performed by two independent endodontists, who were not included in the study and had at least three years of experience, clinically and on the periapical radiographs. Canal fillings terminating at the radiological apex and 2 mm within are 'acceptable'; canal fillings shorter than 2 mm of apex are 'short' and gutta-percha seen beyond radiological apex are considered 'overfilled' ( 21 , 22 ) Statistical Analysis IBM SPSS Version 25 package program (IBM © Corp., Armonk, NY, USA) was used for statistical analysis of data. Normality of distribution was evaluated by using Lilliefor's corrected Kolmogorov-Smirnov test, kurtosis-skewness plots and histograms. In statistical analysis, Pearson's chi-square test was used for categorical data. Exact chi-square test was used if the value observed in the multi-level chi-square test was more than 20% and less than 5%, using standard residual method in post hoc analysis. The non-parametric Kruskal–Wallis H test was performed to compare numerical variables (age, VAS scores) amongst the three groups and the SPSS pairwase comparison module for the post hoc evaluation. The Mann-Whitney U test was used for comparisons of two independent groups. The Friedman test was used to evaluate the changes in pain scores over time. Categorical variables (gender, analgesic intake) were compared amongst the groups using the chi-squared tests. Spearman correlation analysis was used because parametric assumptions were not met in comparisons of two different measurement data. The consistency between the observer evaluations was evaluated with the Cohen's Kappa test. There is no missing data in the data set; and type I error level was set at 0.05. RESULTS Three patients declared their leave from the study after the first visit. Additionaly, total of nine patients, three per group were excluded from the study due to the various reasons such as apical restriction, anxiety, and perforations due to the previous root canal treatment. Thus, they were excluded from the final analysis, that included a total of 108 retreatments were performed on 108 patients (Fig. 1 ). Forty-one of the treated teeth were maxillary incisor, 26 of the treated teeth were maxillary premolar, 6 were mandibular incisor and 35 were mandibular premolar. All the root canals have single root canal. There were not statistically significante difference between the distribution of the types of the teeth from the medicament’s groups. (exact chi-square test, p > 0.05, Table 2) 18 male (50%) and 18 female (50%) patients between the ages of 20–65 were included per group. Patient age groups were divided into three age groups: 20–34, 35–49 and 50–65; and a stratified randomization was performed. When the correlation between age and postoperative pain is evaluated; at 12 hours, patients between the ages of 35–49 had significantly greater pain compared to the patients of 20–34 (p = 0.033) and 50–65 age range (p = 0.017). There was no statistically significant difference at 3, 4 and 7 days except patients between the ages of 35–49 who had significantly more pain compared to patients between the ages of 20–34 (p 0.05), presence of periapical lesion (exact chi-square test, p > 0.05), quality of obturation (exact chi-square test, p > 0.05), type of the coronal restoration (exact chi-square test, p > 0.05), location of the teeth (xact chi-square test, p > 0.05) and presence of fistula (exact chi-square test, p > 0.05). There were no significant differences amongst the tested medicament groups at any of the assessed time intervals based on VAS scores (p > 0.05). Additionally, no statistically significant difference was observed in the tested medicament groups when a periapical lesion is present (Mann-Whitney U test, p > 0.05); while patients with no fistula had significantly gretaer pain values after 24 hours compared to patients with fistula (Pearson chi-square test, p > 0.05; Mann-Whitney U test, p < 0.05). When corralation is tested between the presence of coronal restoration and pain, only patients with coronal restoration had more pain postoperatively at 6 hours (Pearson chi-square test and Mann-Whitney U test, p 0.05). When correlation between the apical extension of the primary root canal fillings and pain was evaluated (Kruskal-Wallis H test); significantly gretaer pain was observed in the short and overextended groups at 24 and 48 hours compared to the cases with acceptable root canal filling levels (p < 0.05). There was no statistically significant difference between the groups in terms of percussion, spontaneous pain and swelling when the level of postoperative pain compared at 48 hours and at 7 days clinical examinations (p > 0.05). The distribution of pain levels experienced by patients in different medications during follow-up periods are shown in Fig. 2 . While the Ca(OH) 2 group had the lowest VAS scores postoperatively, scores were increased after 24 hours, started to decrease at the 48th hour, but started to increase again after the 3rd day. The increase was continued until the 5th day and then a decrease occurred. The Ca(OH) 2 + CHX gel group had a high VAS score at the beginning, and showed a continuous declining trend with the lowest value after 48 hours. The VAS score of the CHX gel group was gretaer compared to scores of the other groups. The Kruskal-Wallis H test was used to evaluate whether there was a difference between the postoperative pain values between the groups at the 6, 12, 24, 48 hours and at 3, 4, 5, 6 and 7 days after the medicament placement. When all the time pain levels observed were evaluated, no statistically significant difference was found between the groups in terms of VAS scores (p > 0.05). When the frequency of drug use was investigated a statistically significant difference was found between groups (Exact chi-square test, p < 0.05). According to the results of Spearman correlation analysis conducted to analyze whether there is a correlation between frequency of drug use and VAS scores, a positive moderate statistically significant correlation was found (Spearman's r = 0.424, p < 0.001) indicating that VAS score increases while also drug use increases. DISCUSSION Postoperative pain following root canal treatment is mostly associated with microorganisms remaining in the root canal system. Eradication of microorganisms is rather harder in retreatment cases due to the presence of remnants of previous root canal filling. As a result, frequency of flare-up was found higher in retreatment cases compared to the flare-up rate of patients with primary root canal treatment ( 4 – 7 ). Thus, using of medicaments after a careful chemomechanical preparation may improve disinfection of root canal system in retreatment cases ( 9 , 10 ). There are limited number of clinical trials examining the effect of the intracanal medicaments on postoperative pain and flare-up incidence in nonsurgical endodontic retreatment. Thus, the present study aimed to evaluate the effect of the three different intracanal medicament on postoperative pain and flare-up incidence in nonsurgical endodontic retreatment. Based on the findings of this study, there was no significant differences among the tested intracanal medicaments; so, the first null hypothesis could not be rejected. If the root canal fillings are exposed to oral environment, contamination with saliva takes place. Saliva contamination leads to bacterial growth and penetration throughout the entire canal ( 4 ). If root canals left open for a long time some bacteria decrease in number or even disappear while the remaining ones may turn into adaptive phenotypes that resist treatment ( 23 ). Postoperative pain and flare-up may develop due to changes in periapical tissue pressure and microbial factors after retreatment ( 24 ). Therefore, in studies evaluating the severity of postoperative pain in nonsurgical endodontic retreatment, the presence and quality of coronal restoration before treatment should be examined. Teeth with marginal defects in coronal restoration demonstrates gretaer postoperative pain after root canal treatment ( 23 ). Contrarily to the previous findings, the present study represented patients with an intact initial coronal restoration had statistically more pain after 6 hours postoperatively compared to the patients whose coronal restoration is lost in the first appointment. A selective process occurs over time that allows anaerobic bacteria to predominate if cavity is sealed after root canals become infected with indigenous oral bacteria ( 25 – 27 ). When pain and the type of bacteria present in root canals are correlated; it was shown that root canals from symptomatic teeth harbored more obligate anaerobes and a bigger number of bacterial species than the asymptomatic teeth ( 28 ). A relationship between systemic diseases such as uncontrolled diabetes, allergic patients, corticosteroid use, and postoperative pain was shown( 4 , 24 ) while a study( 9 ) reported no relationship in between. Thus, only healthy patients with no systemic diseases were included in present study. Also, patients who had not used any analgesic, anti-inflammatory or antibiotics within one week prior to first appointment were chosen; since the long-term effects of antibiotics, analgezics and anti-inflammatory drugs change the perception of postoperative pain. Patients with preoperative pain have greater potential of developing pain and flare-ups after treatment ( 1 , 4 , 9 ). Therefore, cases with pain and swelling were not included in present study. Postoperative pain was recorded greatest within 48 hours after treatment ( 7 , 23 , 29 , 30 ) and the follow-up was usually done for a week ( 23 , 30 , 31 ). Similarly, same follow-up methodology was adapted in present study. Present study considered a stratified randomization design, demonstrating a more reliable correlation between demographic properties and the incidence of postoperative pain, and flare up when compared to the previous studies. Similar to the previous studies ( 9 , 23 , 31 , 32 ) gender of individuals showed no significant correlation with postoperative pain and flare up recorded in medicaments groups. Young patients tend to experience greater pain compared to the pain levels of elderly patients ( 33 ); incidence of flare-up and postoperative pain decreases with age ( 20 ). This phenomenon is attributed to the decreased debris push into the periapical tissues because of narrowing minor foramen over time. Additionally, attenuation of the inflammatory response and the decrease in blood flow also contributes mitigation of symptoms and flare-up. Likewise, in present study, compared to the patients between the ages between 20–34 significantly gretaer pain was recorded in patients between the ages of 35–49 postoperatively 12 hours, 3, 4, and 7 days (p < 0.05). Pressure created by periapical abscess is drained by the fistula; thus, if present, fistula may prevent sudden pain increase and swelling. Risk of acute exacerbation was reported to be small in the presence of fistula ( 4 ). Similarly, in present study, patients with no fistula had significantly gretaer pain at 24 hours postoperatively (p < 0.05). Postoperative pain decreases as the periapical lesion volume sizes increase ( 29 ). This phenomenon might be explained with the presence of sufficient space for pressure distribution in cases with large periapical lesions ( 34 ). However, flare-ups develop less frequently in teeth without apical periodontitis ( 5 ). On the other hand, as the size of periapical lesion increases, the frequency of flare-up development increases ( 35 ). In this study, no statistically significant relationship was detected between the presence of periapical lesions and postoperative pain. Small sample size of studied patients (n = 108) in our study compared the sample size of previously published clinical studies in which sample size increases more than thousand patients may explain why a correlation cannot be found between periapical lesions and postoperative pain ( 6 , 33 ). When postoperative pain was evaluated after retreatment is completed ( 36 ); only teeth with root canal filling 2–4 mm shorter than apex were studied to eliminate the detrimental effect of overextending previous root canal filling on periapical tissues. When the effect of primary root filling levels on postoperative pain after retreatment attempt were evaluated in a recent study, within 24 hours greater pain was experienced by the patients with short initial root canal fillings ( 37 ). In present study, primary root canal treatment is defined "acceptable" if it ends 2 mm shorter or within 2 mm of the radiological apex; "short" if it is positioned more than 2 mm coronally from the radiological apex; and "overextending" if it is beyond the radiological apex. According to our research results, severity of postoperative pain was significantly greater in the cases labelled as short and overextending after 24 and 48 hours postoperatively. It has been reported that the chlorhexidine gel provides 100% inhibition of microorganisms at a depth of 200 µm in the dentinal tubules, reaching a depth of 400 µm from the 1st day and thus showing high spreadability ( 29 , 38 ). When the effect of intra-canal medicaments on postoperative pain was evaluated in a study ( 19 ) 2% chlorhexidine gel and calcium hydroxide + chlorhexidine gel group were more effective in reducing pain than calcium hydroxide group. Rapid and sustained antimicrobial effect of chlorhexidine due to its high diffusivity were pronounced in controlling postoperative pain. Reducing or eliminating lipopolysaccharides associated with clinical symptoms such as spontaneous pain, percussion, and palpation was presented as a part of its pain-controlling mechanism ( 39 ). However, when 2% chlorhexidine is used in irrigation it was reported that 47% lipopolysaccharides was detoxified but it is insufficient to fully inactivate them ( 40 ). When its gel form was placed as a root canal medicament flare-up developed in four cases in the chlorhexidine (0.12%) gel group, whereas no flare-up was observed in the group with calcium hydroxide/camphorated paramonochlorophenol/glycerin paste ( 41 ). However, no statistically significant differences were found. Similarly, in this study, although there were no statistically significant differences between the groups in terms of postoperative pain values, the pain values ​​of the CHX gel group were always the greatest. Flare-up was recorded in chlorhexidine gel group, but only in a single case. Combination of calcium hydroxide and chlorhexidine has a synergistic effect on lipopolysaccharides (endotoxins) produced by gram negative bacteria. Due to the high pH (12.8) of the mixture, the ionization capacity of the chlorhexidine compound increases ( 16 ), while the contact angle of Ca(OH) 2 decreases and thus the wettability of the root canal with medicament increases ( 25 ). As a result, antimicrobial effects of both compounds got increased. In a clinical study postoperative pain got significantly reduced in 2-visit endodontic retreatment design in which Ca(OH) 2 and 0.2% CHX gel mixture was used as an intra-canal medication, compared to the 1-visit treatments ( 24 ). When the effect of intra-canal medicaments on post-operative pain was evaluated ( 19 ), Ca(OH) 2 and 2% CHX mixture was found to be the most effective medication in reducing postoperative pain, followed by the chlorhexidine gel group. The least effective medicament in reducing postoperative pain was Ca(OH) 2 . Similarly, in our study, although there was no statistically significant differences in postoperative pain values ​​between the medicament groups; the Ca(OH) 2 + CHX gel group had a high VAS score at the beginning. However, Ca(OH) 2 + CHX gel combination showed the lowest score after 48 hours and after one week; since, this combination might possesses a synergistic effect against liposaccharides and endotoxins produced by gram-negative bacteria. CONCLUSIONS Postoperative pain and flare-up do not seem to differ when calcium hydroxide or chlorhexidine is used as a intracanal medicament. A similiar degree of pain reduction indicates that calcium hydroxide or chlorhexidine-based medicaments are clinically preferable in retreatment cases to limit postendodontic pain ​​and flare-up incidence. A greater postoperative pain is associated with elderly patients, patients without fistula and patients with initial coronal restoration. In addition, patients with short and overextending previous root canal fillings experienced greater postoperative pain when compared to the patients with acceptable root canal filling levels. We believe greater number of patients with greater number of evaluation parameters should be considered by new clinical studies helping us to control postoperative pain and flare-up. Declarations Author Contributions : Corresponding author Associated Professor Hicran Dönmez Özkan, DDS, PhD was the principal investigator of the study. She organized the study, worked with the department of statistics and wrote the manuscript. Expert in Endodontics Adile Esen Angın, DDS performed patient care and recorded data. Specialty resident İlkim Pınar Saral, DDS assisted to develop ideas, plotting figures and writing of the manuscript. Associated Professor Berdan Aydın, DDS, PhD assisted to develop ideas, plotting figures and writing of the manuscript. Ethics and consent to participate: The study was approved by our university’s Clinical Research Ethics Committee (Protocol ADUDHF2019/063) and Pharmaceuticals and Medical Devices Agency of our country (Protocol 2019/ 079). All participants were first informed about study design and clinical treatment procedures with risks and signed a written informed consent form. Funding: This study was supported by the Adnan Menderes University Research Foundation (DHF- 19010). The Foundation had no role in performing the study, including its design or analysis, or in our decision to publish the findings. Conflict of interest : The authors declare that they have no conflict of interest. References Seltzer S, Naidorf I. Flare-ups in Endodontics: I. Etiological Factors. J Endod. 2004 Jul;30(7):476–81. Alaçam T. Incidence of postoperative pain following the use of different sealers in immediate root canal filling. J Endod. 1985 Mar;11(3):135–7. Sathorn C, Parashos P, Messer H. The prevalence of postoperative pain and flare‐up in single‐ and multiple‐visit endodontic treatment: a systematic review. Int Endod J. 2008 Feb 23;41(2):91–9. Torabinejad M, Kettering JD, McGraw JC, Cummings RR, Dwyer TG, Tobias TS. Factors associated with endodontic interappointment emergencies of teeth with necrotic pulps. J Endod. 1988 Jan;14(5):261–6. Trope M. 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In Vitro Assessment of the Antimicrobial Action and the Mechanical Ability of Chlorhexidine Gel as an Endodontic Irrigant. J Endod. 2001 Jul;27(7):452–5. Gomes BPFA, Souza SFC, Ferraz CCR, Teixeira FB, Zaia AA, Valdrighi L, et al. Effectiveness of 2% chlorhexidine gel and calcium hydroxide against Enterococcus faecalis in bovine root dentine in vitro . Int Endod J. 2003 Apr;36(4):267–75. Turk BT, Sen BH, Ozturk T. In vitro antimicrobial activity of calcium hydroxide mixed with different vehicles against Enterococcus faecalis and Candida albicans. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2009 Aug;108(2):297–301. Ercan E, Dalli M, Türksel Dülgergil Ç, Yaman F. Effect of Intracanal Medication with Calcium Hydroxide and 1% Chlorhexidine in Endodontic Retreatment Cases with Periapical Lesions: An In Vivo Study. Journal of the Formosan Medical Association. 2007;106(3):217–24. Singh RD, Khatter R, Bal RK, Bal CS. Intracanal medications versus placebo in reducing postoperative endodontic pain – a double – blind randomized clinical trial. Braz Dent J. 2013;24(1):25–9. Alonso-Ezpeleta LO, Gasco-Garcia C, Castellanos-Cosano L, Martin-Gonzalez J, Lopez-Frias FJ, Segura-Egea JJ. Postoperative pain after one-visit root-canal treatment on teeth with vital pulps: Comparison of three different obturation techniques. Med Oral Patol Oral Cir Bucal. 2012;e721–7. Sjögren U, Hägglund B, Sundqvist G, Wing K. Factors affecting the long-term results of endodontic treatment. J Endod. 1990 Oct;16(10):498–504. Ørstavik D, Kerekes K, Eriksen HM. The periapical index: A scoring system for radiographic assessment of apical periodontitis. Dental Traumatology. 1986 Feb 27;2(1):20–34. Erdem Hepsenoglu Y, Eyuboglu TF, Özcan M. Postoperative Pain Intensity after Single- versus Two-visit Nonsurgical Endodontic Retreatment: A Randomized Clinical Trial. J Endod. 2018 Sep;44(9):1339–46. Kececi A.D., Celik D. Acute exacerbations in endodontics (Flare-up). Acta Odontologica Turcica. 2003;20(1):61–9. Fabricius L, Dahlén G, Holm SE, Möller AJR. Influence of combinations of oral bacteria on periapical tissues of monkeys. Eur J Oral Sci. 1982 Jun;90(3):200–6. Fabricious L, Dahlen G, Öhman AE, Möller AJR. Predominant indigenous oral bacteria isolated from infected root canals after varied times of closure. Eur J Oral Sci. 1982 Apr;90(2):134–44. Möleer AkeJR, Fabricius L, Dahlén G, Öhman AE, Heyden G. Influence on periapical tissues of indigenous oral bacteria and necrotic pulp tissue in monkeys. Eur J Oral Sci. 1981 Dec;89(6):475–84. Jacinto RC, Gomes BPFA, Ferraz CCR, Zaia AA, Filho FJS. Microbiological analysis of infected root canals from symptomatic and asymptomatic teeth with periapical periodontitis and the antimicrobial susceptibility of some isolated anaerobic bacteria. Oral Microbiol Immunol. 2003 Oct 21;18(5):285–92. Gama TG V., Machado de Oliveira JC, Abad EC, Rôças IN, Siqueira JF. Postoperative pain following the use of two different intracanal medications. Clin Oral Investig. 2008 Dec 10;12(4):325. Basrani B, Tjäderhane L, Santos JM, Pascon E, Grad H, Lawrence HP, et al. Efficacy of chlorhexidine- and calcium hydroxide–containing medicaments against Enterococcus faecalis in vitro. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2003 Nov;96(5):618–24. Aslan T, Dönmez Özkan H. The effect of two calcium silicate‐based and one epoxy resin‐based root canal sealer on postoperative pain: a randomized controlled trial. Int Endod J. 2021 Feb 17;54(2):190–7. Schäfer E, Bossmann K. Antimicrobial efficacy of chloroxylenol and chlorhexidine in the treatment of infected root canals. Am J Dent. 2001 Aug;14(4):233–7. Ng Y ‐L., Glennon JP, Setchell DJ, Gulabivala K. Prevalence of and factors affecting post‐obturation pain in patients undergoing root canal treatment. Int Endod J. 2004 Jun 25;37(6):381–91. Jabeen S, Khurshiduzzaman M. Incidence of post obturation pain following single and multi visit root canal treatment in a teaching hospital of Bangladesh. Mymensingh Med J. 2014 Apr;23(2):254–60. Morse DR, Esposito J V. A clarification on endodontic flare-ups. Oral Surgery, Oral Medicine, Oral Pathology. 1990 Sep;70(3):345–8. Garcia-Font M, Durán-Sindreu F, Morelló S, Irazusta S, Abella F, Roig M, et al. Postoperative pain after removal of gutta-percha from root canals in endodontic retreatment using rotary or reciprocating instruments: a prospective clinical study. Clin Oral Investig. 2018 Sep 2;22(7):2623–31. Glennon JP, Ng Y ‐L., Setchell DJ, Gulabivala K. Prevalence of and factors affecting postpreparation pain in patients undergoing two‐visit root canal treatment. Int Endod J. 2004 Jan 13;37(1):29–37. Yaylali IE, Teke A, Tunca YM. The Effect of Foraminal Enlargement of Necrotic Teeth with a Continuous Rotary System on Postoperative Pain: A Randomized Controlled Trial. J Endod. 2017 Mar;43(3):359–63. Singh RD, Khatter R, Bal RK, Bal CS. Intracanal medications versus placebo in reducing postoperative endodontic pain – a double – blind randomized clinical trial. Braz Dent J. 2013;24(1):25–9. Gomes BPFA, Aveiro E, Kishen A. Irrigants and irrigation activation systems in Endodontics. Braz Dent J. 2023 Aug;34(4):1–33. Yoldas O, Topuz A, Isçi AS, Oztunc H. Postoperative pain after endodontic retreatment: Single- versus two-visit treatment. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2004 Oct;98(4):483–7. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4090764","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":281151369,"identity":"245408c3-02bb-4ac8-b2f1-f9f1f64526e7","order_by":0,"name":"Adile Esen Angın","email":"","orcid":"","institution":"Aydın Adnan Menderes University","correspondingAuthor":false,"prefix":"","firstName":"Adile","middleName":"Esen","lastName":"Angın","suffix":""},{"id":281151370,"identity":"b3352542-0992-45b9-9704-d47716f63874","order_by":1,"name":"Hicran Dönmez Özkan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIiWNgGAWjYBACA2YwBSEZPjaASMbGA0RrYZzZwCABpBrwa2FA0sLMC9bCwIBXizk787MPP3dYy5mLHT782XaHTZ1u+2GgLTU20bi0WDazGc/sPZNubDk7LcE490yahNmZRKCWY2m5DbgcdpiHmYG37XDihts5Bsm5bYclzA4AtTA2HMarhfEvWEv+h8OWIC3nHxLWwgy1hbGZEaTlBkFb2IyZZdvSjQ1upxkz9ralSW67AbQlAZ9fzh9+zPi2zVrO4Hby4w8/22z4zc6nP3zwocYGpxYcIIE05aNgFIyCUTAK0AAARvJgU6UIRjsAAAAASUVORK5CYII=","orcid":"","institution":"Aydın Adnan Menderes University","correspondingAuthor":true,"prefix":"","firstName":"Hicran","middleName":"Dönmez","lastName":"Özkan","suffix":""},{"id":281151371,"identity":"46ca254a-bf80-4f19-add1-febf7fe35324","order_by":2,"name":"İlkim Pınar Saral","email":"","orcid":"","institution":"Aydın Adnan Menderes University","correspondingAuthor":false,"prefix":"","firstName":"İlkim","middleName":"Pınar","lastName":"Saral","suffix":""},{"id":281151372,"identity":"41bdebc3-7f62-4ad5-bc8b-c42a6c70185d","order_by":3,"name":"Berdan Aydın","email":"","orcid":"","institution":"Dokuz Eylül University","correspondingAuthor":false,"prefix":"","firstName":"Berdan","middleName":"","lastName":"Aydın","suffix":""}],"badges":[],"createdAt":"2024-03-13 09:04:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4090764/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4090764/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00784-024-05760-w","type":"published","date":"2024-06-08T14:47:28+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":53195640,"identity":"65aab070-bad2-4067-b414-9db6b559ad2c","added_by":"auto","created_at":"2024-03-21 18:25:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36472,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Figure1.pdf.png","url":"https://assets-eu.researchsquare.com/files/rs-4090764/v1/f52e5e8c86c97f65f57ab182.png"},{"id":53195641,"identity":"91c9c8bf-60bd-4942-b52b-34aa60e85cfd","added_by":"auto","created_at":"2024-03-21 18:25:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":214219,"visible":true,"origin":"","legend":"\u003cp\u003eBoxplot chart shows mean pain values and reduction in pain over-time.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4090764/v1/091092a37249a12dfae771e2.png"},{"id":58821963,"identity":"dba6113a-a680-4c0d-92ea-697eecd4e94f","added_by":"auto","created_at":"2024-06-21 16:20:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":855910,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4090764/v1/18762b8f-5fda-48d0-b7db-1688b9d7096a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Incidence and Intensity of Postoperative Pain and Flare-up Following the Use of Three Different Intracanal Medicaments In Teeth With Posttreatment Apical Periodontitis: A Randomized Clinical Trial","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePostoperative pain and flare-up are among clinical complications encountered during and after endodontic treatment (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Although endodontic treatment done using contemporary techniques provides appropriate biological results, preventing pain during and after the treatment is as much desired (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Postoperative pain occurs as a result of many factors such as presence of pain preoperatively and procedural variations. Factors such as gender and age, presence of a systemic disease, condition of the pulp, presence of preoperative pain, number of appointments, use of intra-canal medications and localization of the tooth in the arch may stimulate postoperative pain and flare-up (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Many studies were reported that the frequency of flare-up is higher in retreatment cases compared to the flare-up rate of patients with primary root canal treatment (\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). One of the most important causes of postoperative pain is microorganisms that cannot be eliminated from the root canal. Microbial flora in cases with unsuccessful endodontic treatment history is different from that of primary root canal infections. \u003cem\u003eEnterococcus faecalis\u003c/em\u003e constitutes a small part of the flora in cases where root canal treatment is performed for the first time, while plays a major role in the etiology of persistent periradicular infections with root canal treatment (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Therefore, in retreatment procedures; although microbial eradication is mainly achieved by the chemomechanical preparation, root canal medicaments may help in disinfection of the root canal (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCalcium hydroxide is the most used canal dressing in endodontic practice since the early 1930s (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Although it is the most preferred medication, it does not show an equal effect against all the bacterial species in the root canal system (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eChlorhexidine, which has been widely used in dentistry since the 1970s, was recommended in irrigation and as an intra-canal disinfectant in endodontics. In a study, its solutions, gels, and controlled release preparations were found effective against resistant microorganisms such as \u003cem\u003eEnterococcus faecalis\u003c/em\u003e and \u003cem\u003eCandida albicans\u003c/em\u003e (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Owing to its viscosity, chlorhexidine gel was found better in mechanical cleaning compared to its liquid counterpart (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). A study reported that when used as an intra-canal disinfectant, chlorhexidine is more effective than calcium hydroxide against \u003cem\u003eE. faecalis\u003c/em\u003e (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). However, chlorhexidine alone can not form a physical barrier and cannot provide radiopacity (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e); thus, its use combined with calcium hydroxide may offer such features.\u003c/p\u003e \u003cp\u003eSynergistic effect of chlorhexidine and calcium hydroxide mixture increase antimicrobial activity of calcium hydroxide while preserving its barrier function (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). There is limited knowledge about the effectiveness of this combination on postoperative pain and flare-up incidence in retreatment cases.\u003c/p\u003e \u003cp\u003eTherefore, the aim of this study is to the evaluate the effect of chlorhexidine, calcium hydroxide and chlorhexidine and calcium hydroxide mixture as intra-canal medicaments on postoperative pain and flare-up incidence and on the frequency of analgesic use in teeth with PTAP. The null hypothesis tested in this study is that the type of intra-canal medicaments used would not affect the incidence and the intensity of post-treatment endodontic pain and flare-up incidence.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eThe research protocol was recorded in \u003cspan\u003e\u003cspan\u003ewww.ClinicalTrials.gov\u003c/span\u003e\u003c/span\u003e database (National Library of Medicine 8600 Rockville Pike, Bethesda, MD 20894, United States) under ID NCT05052814 and the study was approved by our university\u0026rsquo;s Clinical Research Ethics Committee (Protocol ADUDHF2019/063) and Pharmaceuticals and Medical Devices Agency of our country (Protocol 2019/ 079).\u003c/p\u003e\n\u003cp\u003eThe minimal estimated sample size for each group was computed as 34 based on a previous research data (\u003cspan\u003e20\u003c/span\u003e) (alpha-type error of 0.05, a beta power of 0.95 was specified by G*power V.3.1.9.2 software (Heinrich Heine, University of D\u0026uuml;sseldorf, D\u0026uuml;sseldorf, Germany). To increase the stastical power and considering the potential patient dropouts, 40 patients per group were enrolled. Thus, a total of 114 patients were included in this study.\u003c/p\u003e\n\u003cdiv id=\"Sec3\"\u003e\n \u003ch2\u003ePatient Selection and Eligibility Criteria\u003c/h2\u003e\n \u003cp\u003eThe patients were selected from those referred to the Hospital of Aydın Adnan Menderes University of Dental Faculty from March 2019 to August 2020. All patients meeting the inclusion criteria were invited to the participate in the study. One hundred-twenty systematically healthy patients aged between 20 to 65 years met the criteria and agreed to participate in the study. Patients who had root canal treated single-rooted incisior or mandibular premolar teeth with a single root canal at least or equal three years ago but still had PTAP were included in this study. Failure of the previous root canal treatment was determeined by clinical and radiographic examinations. Teeth with clinal signs and semptoms for the requirement of retreatment except cases with preoperative swelling, spontaneous pain, severe percussion and palpation were included in this study.\u003c/p\u003e\n \u003cp\u003eAll inclusion and exclusion criteria are listed in Table \u003cspan\u003e1\u003c/span\u003e. All participants were first informed about study design and clinical treatment procedures with risks and signed a written informed consent form.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e.\u0026nbsp;Inclusion/exclusion criteria of the participants\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"964\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eINCLUSION CRITERIA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEXCLUSION CRITERIA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients between 20 - 65 years of ages\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003ePregnant patients \u0026nbsp;and \u0026nbsp;patients in lactation period\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients who agree to participate this study\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003eHaving used corticosteroids in the last 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients had not used analgesic or antibiotics in last 7 days\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003eIndividuals with systemic diseases (endocarditis, immune system diseases,etc.) requiring antibiotic prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle root and single-canal incisor, canine, premolar teeth that have been endodontically treated only once\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003eHaving received immunosuppressive therapy within the last week\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAsymptomatic teeth with previous endodontic treatment but with abscess experience or pain on chewing/percussion history developed within last 12 months.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003ePatients who had systemic or \u0026nbsp; \u0026nbsp; allergic sensitivty for the NSAIDs and local ananesthetics\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTeeth, although asymtomatic, but with newly developed periapical radiolucency within two years compared to the radiographic findings present 2 years ago at the time of root canal tretament was done.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003eThe presence of advanced periodontal disease (probing depth \u0026gt; 4 mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTeeth with periapical radiolucency, but with increased or unchanged according to pre-treatment radiography\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003eThe presence of a foreign body in the root canal that prevents entry (broken file, post, etc.)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients with good oral hygiene\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003eFracture or crack in the root\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003eTeeth that cannot reach the working length due to calcification in the root canal and step formation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003eTeeth that cannot be restored due to excessive loss of material in the coronal structure\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003eThe presence of more than one adjacent tooth requiring endodontic treatment that may cause reflected pain in the same patient.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.74611398963731%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"47.25388601036269%\" valign=\"top\"\u003e\n \u003cp\u003eTeeth that develop any complications ( breakage of endodontic file, perforation, inability to determine the working length with the apex finder) during the removal of the canal filling material.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Distribution of the types of the teeth from the medicament\u0026rsquo;s groups.\u003c/p\u003e\n \u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1711002065.png\"\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRandom Sequence Generation and Allocation Concealment\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\"\u003e\n \u003cp\u003eThe volunteers were randomly assigned to three different medicament groups. The allocation was performed according to Consolidated Standards of Reporting Trials 2010. Stratified randomization was performed for each group according to gender and age. After patients were divided based on gender and age-groups, they were randomly placed in the medicament groups to make an equal distribution of the type of medicament used. To implement a random placement of patients, different blocks were designed with the combination of covariates; and a simple randomization procedure, envelope selection, was applied within each block to assign participants to one of the blocks.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\"\u003e\n \u003ch2\u003eTreatment Protocol\u003c/h2\u003e\n \u003cp\u003eAll root canal treatments were performed by the same clinician. During diagnostic examination, periapical radiographs were obtained using a phosphor plate (Vistascan Mini Easy, D\u0026uuml;rr Dental) and using the long-cone paralleling technique under standard exposure conditions and recorded. After the clinical and radiographic evaluations of relevant teeth; the findings including spontaneous pain, swelling, fistula, restoration type and condition, caries, fractures were recorded on the case report forms. Tests such as percussion, palpation, mobility and periodontal probing were performed to determine the presence of preoperative pain. All patients were received 2-visit root canal retreatments.\u003c/p\u003e\n \u003cp\u003eAfter administration of local anaesthesia (2 mL, 4% articaine hydrochloride containing 1:100 000 adrenalin), a rubber dam was applied for the isolation. No additional local anesthesia was given since patient comfort was provided with delivered amount. Following the preparation of the access cavity, ProTaper Universal Retreatment files (Dentsply Maillefer, Ballaigues, Switzerland) were used at 500 rpm and 3 Ncm torque to remove the root canal filling. D1 file (30 / .09) was used in the coronal third, D2 file (25 / .08) in the middle third, and D3 file (20 / .07) in the apical third region. Working length was determined to be 1 mm shorter than the value (0.0) indicated by the electronic apex locator (Raypex 6, VDW, Munich, Germany) and confirmed radiographically. Apical patency was established with a size 10 K-file. Next, shaping procedure was completed at the working length using ProTaper Next rotary files: X1, X2 and X3 (Dentsply Maillefer, Ballaigues, Switzerland), respectively. In large canals where the use of X3 files result in under-instrumentation of apex, shaping was completed with X4 and X5 files. No chemical solvent was used to remove the previous root canal fillings. A 27-gauge notched type irrigation needle (Endo Eze; Ultradent Products Inc. South Jordan, USA) was placed loosly 2 mm shorter of working length while performing 2 mL, 5.25% NaOCl irrigation between each file. After the last used file, shaping for retreatment was considered complete when there is no residual canal filling observed under 2.5x magnification and the irrigation solution is clear from debris. Then, a periapical radiograph was taken to verify complete removal of the filing materials. If any remaning material is visible on the radiograph, shaping was completed with X4 and X5 files and a size # 50 Hedstr\u0026ouml;m file was used until a complete removal of previous filling is achieved. After that, final irrigation was done under activation (Endoactivator, Dentsply, Tulsa, USA) using 2 mL of 17% EDTA followed by 4 mL of 5.25% NaOCl. Endoactivator was run for 20 seconds between 1 mL 5.25% NaOCl irrigation. Root canal was rinsed with sterile distilled water and dried with sterile paper-points. Finally, medicaments were placed with a lentulo spiral (Dentsply Maillefer, Switzerland) as follows:\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCalcium hydroxide paste (Ultracal XS; Ultradent South Jordan, USA)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e2% Chlorhexidine gel (Gluko-Chex, Cerkamed, Stalowa Wola, Poland)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eEqual amounts of calcium hydroxide (Ultracal XS; Ultradent South Jordan, USA) and chlorhexidine gel (Gluco-Chex, Cerkamed, Stalowa Wola, Poland) were mixed and placed.\u003c/p\u003e\n \u003cp\u003eAfter the visual observation of the canals filled with medicament, sterile teflon tape was placed in the canal orifice and the access cavity was sealed with glass ionomer cement (Kavitan \u0026trade; Plus; Pentron, SpofaDental, Czech Republic).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\"\u003e\n \u003ch2\u003ePostoperative Pain Evaluation\u003c/h2\u003e\n \u003cp\u003ePostoperative pain levels were evaluated for seven days using a VAS scale. Post operative pain scores were recorded at 6, 12 hours and at 1, 2, 3, 4, 5, 6 and 7 days after the medicaments were placed. In the VAS scale given to the patient two opposite limits of the parameter are marked on both ends of a line prepared as 0-100 mm. According to the scale, while \u0026apos;no pain\u0026apos; is marked with zero, \u0026apos;unbearable pain\u0026apos; is marked with 100 on the line (\u003cspan\u003e21\u003c/span\u003e). The patients were asked to evaluate own pain status by marking the line on the specified days and times. Patients who could not communicate to submit the evaluation forms were excluded from the study. The patients were prescribed 400 mg ibuprofen (Brufen, Abbott, IL, USA) and instructed to use only for severe pain. Frequency and time of use of analgesics were recorded. In addition to the documentation, oral examinations were performed on the 48th hour and at 7 days. Sensitivity on percussion, spontaneous pain, swelling of surrounding tissues and antibiotic requirement were also examined and recorded.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\"\u003e\n \u003ch2\u003eEvaluation of Previous Root Canal Filling Level\u003c/h2\u003e\n \u003cp\u003eEvaluation of the status of primary root canal fillings was performed by two independent endodontists, who were not included in the study and had at least three years of experience, clinically and on the periapical radiographs. Canal fillings terminating at the radiological apex and 2 mm within are \u0026apos;acceptable\u0026apos;; canal fillings shorter than 2 mm of apex are \u0026apos;short\u0026apos; and gutta-percha seen beyond radiological apex are considered \u0026apos;overfilled\u0026apos; (\u003cspan\u003e21\u003c/span\u003e, \u003cspan\u003e22\u003c/span\u003e)\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n \u003cp\u003eIBM SPSS Version 25 package program (IBM \u0026copy; Corp., Armonk, NY, USA) was used for statistical analysis of data. Normality of distribution was evaluated by using Lilliefor\u0026apos;s corrected Kolmogorov-Smirnov test, kurtosis-skewness plots and histograms. In statistical analysis, Pearson\u0026apos;s chi-square test was used for categorical data. Exact chi-square test was used if the value observed in the multi-level chi-square test was more than 20% and less than 5%, using standard residual method in post hoc analysis.\u003c/p\u003e\n \u003cp\u003eThe non-parametric Kruskal\u0026ndash;Wallis H test was performed to compare numerical variables (age, VAS scores) amongst the three groups and the SPSS pairwase comparison module for the post hoc evaluation. The Mann-Whitney U test was used for comparisons of two independent groups. The Friedman test was used to evaluate the changes in pain scores over time. Categorical variables (gender, analgesic intake) were compared amongst the groups using the chi-squared tests. Spearman correlation analysis was used because parametric assumptions were not met in comparisons of two different measurement data. The consistency between the observer evaluations was evaluated with the Cohen\u0026apos;s Kappa test. There is no missing data in the data set; and type I error level was set at 0.05.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThree patients declared their leave from the study after the first visit. Additionaly, total of nine patients, three per group were excluded from the study due to the various reasons such as apical restriction, anxiety, and perforations due to the previous root canal treatment. Thus, they were excluded from the final analysis, that included a total of 108 retreatments were performed on 108 patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Forty-one of the treated teeth were maxillary incisor, 26 of the treated teeth were maxillary premolar, 6 were mandibular incisor and 35 were mandibular premolar. All the root canals have single root canal. There were not statistically significante difference between the distribution of the types of the teeth from the medicament\u0026rsquo;s groups. (exact chi-square test, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Table\u0026nbsp;2)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e18 male (50%) and 18 female (50%) patients between the ages of 20\u0026ndash;65 were included per group. Patient age groups were divided into three age groups: 20\u0026ndash;34, 35\u0026ndash;49 and 50\u0026ndash;65; and a stratified randomization was performed. When the correlation between age and postoperative pain is evaluated; at 12 hours, patients between the ages of 35\u0026ndash;49 had significantly greater pain compared to the patients of 20\u0026ndash;34 (p\u0026thinsp;=\u0026thinsp;0.033) and 50\u0026ndash;65 age range (p\u0026thinsp;=\u0026thinsp;0.017). There was no statistically significant difference at 3, 4 and 7 days except patients between the ages of 35\u0026ndash;49 who had significantly more pain compared to patients between the ages of 20\u0026ndash;34 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eNo significant differences were observed in any of the following parameters: gender (exact chi-square test, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), presence of periapical lesion (exact chi-square test, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), quality of obturation (exact chi-square test, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), type of the coronal restoration (exact chi-square test, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), location of the teeth (xact chi-square test, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) and presence of fistula (exact chi-square test, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eThere were no significant differences amongst the tested medicament groups at any of the assessed time intervals based on VAS scores (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Additionally, no statistically significant difference was observed in the tested medicament groups when a periapical lesion is present (Mann-Whitney U test, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05); while patients with no fistula had significantly gretaer pain values after 24 hours compared to patients with fistula (Pearson chi-square test, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Mann-Whitney U test, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eWhen corralation is tested between the presence of coronal restoration and pain, only patients with coronal restoration had more pain postoperatively at 6 hours (Pearson chi-square test and Mann-Whitney U test, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eNo significant difference was found between the apical extension of the previous canal fillings in different medicament groups (Exact chi-square test, x\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;3.836, df\u0026thinsp;=\u0026thinsp;4, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). When correlation between the apical extension of the primary root canal fillings and pain was evaluated (Kruskal-Wallis H test); significantly gretaer pain was observed in the short and overextended groups at 24 and 48 hours compared to the cases with acceptable root canal filling levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eThere was no statistically significant difference between the groups in terms of percussion, spontaneous pain and swelling when the level of postoperative pain compared at 48 hours and at 7 days clinical examinations (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eThe distribution of pain levels experienced by patients in different medications during follow-up periods are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. While the Ca(OH)\u003csub\u003e2\u003c/sub\u003e group had the lowest VAS scores postoperatively, scores were increased after 24 hours, started to decrease at the 48th hour, but started to increase again after the 3rd day. The increase was continued until the 5th day and then a decrease occurred. The Ca(OH)\u003csub\u003e2\u003c/sub\u003e + CHX gel group had a high VAS score at the beginning, and showed a continuous declining trend with the lowest value after 48 hours. The VAS score of the CHX gel group was gretaer compared to scores of the other groups.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe Kruskal-Wallis H test was used to evaluate whether there was a difference between the postoperative pain values between the groups at the 6, 12, 24, 48 hours and at 3, 4, 5, 6 and 7 days after the medicament placement. When all the time pain levels observed were evaluated, no statistically significant difference was found between the groups in terms of VAS scores (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eWhen the frequency of drug use was investigated a statistically significant difference was found between groups (Exact chi-square test, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). According to the results of Spearman correlation analysis conducted to analyze whether there is a correlation between frequency of drug use and VAS scores, a positive moderate statistically significant correlation was found (Spearman's r\u0026thinsp;=\u0026thinsp;0.424, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) indicating that VAS score increases while also drug use increases.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003ePostoperative pain following root canal treatment is mostly associated with microorganisms remaining in the root canal system. Eradication of microorganisms is rather harder in retreatment cases due to the presence of remnants of previous root canal filling. As a result, frequency of flare-up was found higher in retreatment cases compared to the flare-up rate of patients with primary root canal treatment (\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Thus, using of medicaments after a careful chemomechanical preparation may improve disinfection of root canal system in retreatment cases (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). There are limited number of clinical trials examining the effect of the intracanal medicaments on postoperative pain and flare-up incidence in nonsurgical endodontic retreatment. Thus, the present study aimed to evaluate the effect of the three different intracanal medicament on postoperative pain and flare-up incidence in nonsurgical endodontic retreatment. Based on the findings of this study, there was no significant differences among the tested intracanal medicaments; so, the first null hypothesis could not be rejected.\u003c/p\u003e \u003cp\u003eIf the root canal fillings are exposed to oral environment, contamination with saliva takes place. Saliva contamination leads to bacterial growth and penetration throughout the entire canal (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). If root canals left open for a long time some bacteria decrease in number or even disappear while the remaining ones may turn into adaptive phenotypes that resist treatment (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Postoperative pain and flare-up may develop due to changes in periapical tissue pressure and microbial factors after retreatment (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Therefore, in studies evaluating the severity of postoperative pain in nonsurgical endodontic retreatment, the presence and quality of coronal restoration before treatment should be examined. Teeth with marginal defects in coronal restoration demonstrates gretaer postoperative pain after root canal treatment (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Contrarily to the previous findings, the present study represented patients with an intact initial coronal restoration had statistically more pain after 6 hours postoperatively compared to the patients whose coronal restoration is lost in the first appointment. A selective process occurs over time that allows anaerobic bacteria to predominate if cavity is sealed after root canals become infected with indigenous oral bacteria (\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). When pain and the type of bacteria present in root canals are correlated; it was shown that root canals from symptomatic teeth harbored more obligate anaerobes and a bigger number of bacterial species than the asymptomatic teeth (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA relationship between systemic diseases such as uncontrolled diabetes, allergic patients, corticosteroid use, and postoperative pain was shown(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) while a study(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) reported no relationship in between. Thus, only healthy patients with no systemic diseases were included in present study. Also, patients who had not used any analgesic, anti-inflammatory or antibiotics within one week prior to first appointment were chosen; since the long-term effects of antibiotics, analgezics and anti-inflammatory drugs change the perception of postoperative pain.\u003c/p\u003e \u003cp\u003ePatients with preoperative pain have greater potential of developing pain and flare-ups after treatment (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Therefore, cases with pain and swelling were not included in present study.\u003c/p\u003e \u003cp\u003ePostoperative pain was recorded greatest within 48 hours after treatment (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) and the follow-up was usually done for a week (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Similarly, same follow-up methodology was adapted in present study.\u003c/p\u003e \u003cp\u003ePresent study considered a stratified randomization design, demonstrating a more reliable correlation between demographic properties and the incidence of postoperative pain, and flare up when compared to the previous studies. Similar to the previous studies (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) gender of individuals showed no significant correlation with postoperative pain and flare up recorded in medicaments groups.\u003c/p\u003e \u003cp\u003eYoung patients tend to experience greater pain compared to the pain levels of elderly patients (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e); incidence of flare-up and postoperative pain decreases with age (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). This phenomenon is attributed to the decreased debris push into the periapical tissues because of narrowing minor foramen over time. Additionally, attenuation of the inflammatory response and the decrease in blood flow also contributes mitigation of symptoms and flare-up. Likewise, in present study, compared to the patients between the ages between 20\u0026ndash;34 significantly gretaer pain was recorded in patients between the ages of 35\u0026ndash;49 postoperatively 12 hours, 3, 4, and 7 days (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003ePressure created by periapical abscess is drained by the fistula; thus, if present, fistula may prevent sudden pain increase and swelling. Risk of acute exacerbation was reported to be small in the presence of fistula (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Similarly, in present study, patients with no fistula had significantly gretaer pain at 24 hours postoperatively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003ePostoperative pain decreases as the periapical lesion volume sizes increase (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). This phenomenon might be explained with the presence of sufficient space for pressure distribution in cases with large periapical lesions (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). However, flare-ups develop less frequently in teeth without apical periodontitis (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). On the other hand, as the size of periapical lesion increases, the frequency of flare-up development increases (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). In this study, no statistically significant relationship was detected between the presence of periapical lesions and postoperative pain. Small sample size of studied patients (n\u0026thinsp;=\u0026thinsp;108) in our study compared the sample size of previously published clinical studies in which sample size increases more than thousand patients may explain why a correlation cannot be found between periapical lesions and postoperative pain (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhen postoperative pain was evaluated after retreatment is completed (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e); only teeth with root canal filling 2\u0026ndash;4 mm shorter than apex were studied to eliminate the detrimental effect of overextending previous root canal filling on periapical tissues. When the effect of primary root filling levels on postoperative pain after retreatment attempt were evaluated in a recent study, within 24 hours greater pain was experienced by the patients with short initial root canal fillings (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). In present study, primary root canal treatment is defined \"acceptable\" if it ends 2 mm shorter or within 2 mm of the radiological apex; \"short\" if it is positioned more than 2 mm coronally from the radiological apex; and \"overextending\" if it is beyond the radiological apex. According to our research results, severity of postoperative pain was significantly greater in the cases labelled as short and overextending after 24 and 48 hours postoperatively.\u003c/p\u003e \u003cp\u003eIt has been reported that the chlorhexidine gel provides 100% inhibition of microorganisms at a depth of 200 \u0026micro;m in the dentinal tubules, reaching a depth of 400 \u0026micro;m from the 1st day and thus showing high spreadability (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). When the effect of intra-canal medicaments on postoperative pain was evaluated in a study (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) 2% chlorhexidine gel and calcium hydroxide\u0026thinsp;+\u0026thinsp;chlorhexidine gel group were more effective in reducing pain than calcium hydroxide group. Rapid and sustained antimicrobial effect of chlorhexidine due to its high diffusivity were pronounced in controlling postoperative pain. Reducing or eliminating lipopolysaccharides associated with clinical symptoms such as spontaneous pain, percussion, and palpation was presented as a part of its pain-controlling mechanism (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). However, when 2% chlorhexidine is used in irrigation it was reported that 47% lipopolysaccharides was detoxified but it is insufficient to fully inactivate them (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). When its gel form was placed as a root canal medicament flare-up developed in four cases in the chlorhexidine (0.12%) gel group, whereas no flare-up was observed in the group with calcium hydroxide/camphorated paramonochlorophenol/glycerin paste (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). However, no statistically significant differences were found. Similarly, in this study, although there were no statistically significant differences between the groups in terms of postoperative pain values, the pain values ​​of the CHX gel group were always the greatest. Flare-up was recorded in chlorhexidine gel group, but only in a single case.\u003c/p\u003e \u003cp\u003eCombination of calcium hydroxide and chlorhexidine has a synergistic effect on lipopolysaccharides (endotoxins) produced by gram negative bacteria. Due to the high pH (12.8) of the mixture, the ionization capacity of the chlorhexidine compound increases (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), while the contact angle of Ca(OH)\u003csub\u003e2\u003c/sub\u003e decreases and thus the wettability of the root canal with medicament increases (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). As a result, antimicrobial effects of both compounds got increased. In a clinical study postoperative pain got significantly reduced in 2-visit endodontic retreatment design in which Ca(OH)\u003csub\u003e2\u003c/sub\u003e and 0.2% CHX gel mixture was used as an intra-canal medication, compared to the 1-visit treatments (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). When the effect of intra-canal medicaments on post-operative pain was evaluated (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), Ca(OH)\u003csub\u003e2\u003c/sub\u003e and 2% CHX mixture was found to be the most effective medication in reducing postoperative pain, followed by the chlorhexidine gel group. The least effective medicament in reducing postoperative pain was Ca(OH)\u003csub\u003e2\u003c/sub\u003e. Similarly, in our study, although there was no statistically significant differences in postoperative pain values ​​between the medicament groups; the Ca(OH)\u003csub\u003e2\u003c/sub\u003e + CHX gel group had a high VAS score at the beginning. However, Ca(OH)\u003csub\u003e2\u003c/sub\u003e + CHX gel combination showed the lowest score after 48 hours and after one week; since, this combination might possesses a synergistic effect against liposaccharides and endotoxins produced by gram-negative bacteria.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003ePostoperative pain and flare-up do not seem to differ when calcium hydroxide or chlorhexidine is used as a intracanal medicament. A similiar degree of pain reduction indicates that calcium hydroxide or chlorhexidine-based medicaments are clinically preferable in retreatment cases to limit postendodontic pain ​​and flare-up incidence.\u003c/p\u003e \u003cp\u003eA greater postoperative pain is associated with elderly patients, patients without fistula and patients with initial coronal restoration. In addition, patients with short and overextending previous root canal fillings experienced greater postoperative pain when compared to the patients with acceptable root canal filling levels. We believe greater number of patients with greater number of evaluation parameters should be considered by new clinical studies helping us to control postoperative pain and flare-up.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e: Corresponding author Associated Professor Hicran D\u0026ouml;nmez \u0026Ouml;zkan, DDS, PhD was the principal investigator of the study. She organized the study, worked with the department of statistics and wrote the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eExpert in Endodontics Adile Esen Angın, DDS performed patient care and recorded data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSpecialty resident İlkim Pınar Saral, DDS assisted to develop ideas, plotting figures and writing of the manuscript. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAssociated Professor Berdan Aydın, DDS, PhD assisted to develop ideas, plotting figures and writing of the manuscript. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study was approved by our university\u0026rsquo;s Clinical Research Ethics Committee (Protocol ADUDHF2019/063) and Pharmaceuticals and Medical Devices Agency of our country (Protocol 2019/ 079).\u0026nbsp;All participants were first informed about study design and clinical treatment procedures with risks and signed a written informed consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This study was supported by the Adnan Menderes University Research Foundation (DHF- 19010). The Foundation had no role in performing the study, including its design or analysis, or in our decision to publish the findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e: The authors declare that they have no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSeltzer S, Naidorf I. Flare-ups in Endodontics: I. Etiological Factors. J Endod. 2004 Jul;30(7):476\u0026ndash;81. \u003c/li\u003e\n\u003cli\u003eAla\u0026ccedil;am T. Incidence of postoperative pain following the use of different sealers in immediate root canal filling. J Endod. 1985 Mar;11(3):135\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eSathorn C, Parashos P, Messer H. The prevalence of postoperative pain and flare‐up in single‐ and multiple‐visit endodontic treatment: a systematic review. Int Endod J. 2008 Feb 23;41(2):91\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eTorabinejad M, Kettering JD, McGraw JC, Cummings RR, Dwyer TG, Tobias TS. Factors associated with endodontic interappointment emergencies of teeth with necrotic pulps. J Endod. 1988 Jan;14(5):261\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eTrope M. Flare‐up rate of single‐visit endodontics. Int Endod J. 1991 Jan 25;24(1):24\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eImura N, Zuolo ML. Factors associated with endodontic flare‐ups: a prospective study. Int Endod J. 1995 Sep 25;28(5):261\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eTsesis I, Faivishevsky V, Fuss Z, Zukerman O. Flare-ups after Endodontic Treatment: A Meta-analysis of Literature. J Endod. 2008 Oct;34(10):1177\u0026ndash;81. \u003c/li\u003e\n\u003cli\u003eHancock HH, Sigurdsson A, Trope M, Moiseiwitsch J. Bacteria isolated after unsuccessful endodontic treatment in a North American population. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2001 May;91(5):579\u0026ndash;86. \u003c/li\u003e\n\u003cli\u003eWalton R, Fouad A. Endodontic interappointment flare-Ups: A prospective study of incidence and related factors. J Endod. 1992 Apr;18(4):172\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eWalton R, Holtonjr I, Michelich R. Calcium Hydroxide as an Intracanal Medication: Effect on Posttreatment Pain. J Endod. 2003 Oct;29(10):627\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eBystr\u0026ouml;m A, Claesson R, Sundqvist G. The antibacterial effect of camphorated paramonochlorophenol, camphorated phenol and calcium hydroxide in the treatment of infected root canals. Dental Traumatology. 1985 Oct 27;1(5):170\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eFigueiredo de Almeida Gomes BP, Vianna ME, Sena NT, Zaia AA, Ferraz CCR, de Souza Filho FJ. In vitro evaluation of the antimicrobial activity of calcium hydroxide combined with chlorhexidine gel used as intracanal medicament. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2006 Oct;102(4):544\u0026ndash;50. \u003c/li\u003e\n\u003cli\u003eMolander A, Reit C, Dahlen G, Kvist T. Microbiological status of root-filled teeth with apical periodontitis. Int Endod J. 1998;31(1):1\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eErcan E, Ozekinci T, Atakul F, G\u0026uuml;l K. Antibacterial Activity of 2% Chlorhexidine Gluconate and 5.25% Sodium Hypochlorite in Infected Root Canal: In Vivo Study. J Endod. 2004 Feb;30(2):84\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eFerraz C, de Almeida Gomes B, ZAIA A, TEIXEIRA F, de Souza-Filho F. In Vitro Assessment of the Antimicrobial Action and the Mechanical Ability of Chlorhexidine Gel as an Endodontic Irrigant. J Endod. 2001 Jul;27(7):452\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eGomes BPFA, Souza SFC, Ferraz CCR, Teixeira FB, Zaia AA, Valdrighi L, et al. Effectiveness of 2% chlorhexidine gel and calcium hydroxide against \u003cem\u003eEnterococcus faecalis\u003c/em\u003e in bovine root dentine \u003cem\u003ein\u0026emsp;vitro\u003c/em\u003e. Int Endod J. 2003 Apr;36(4):267\u0026ndash;75. \u003c/li\u003e\n\u003cli\u003eTurk BT, Sen BH, Ozturk T. In vitro antimicrobial activity of calcium hydroxide mixed with different vehicles against Enterococcus faecalis and Candida albicans. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2009 Aug;108(2):297\u0026ndash;301. \u003c/li\u003e\n\u003cli\u003eErcan E, Dalli M, T\u0026uuml;rksel D\u0026uuml;lgergil \u0026Ccedil;, Yaman F. Effect of Intracanal Medication with Calcium Hydroxide and 1% Chlorhexidine in Endodontic Retreatment Cases with Periapical Lesions: An In Vivo Study. Journal of the Formosan Medical Association. 2007;106(3):217\u0026ndash;24. \u003c/li\u003e\n\u003cli\u003eSingh RD, Khatter R, Bal RK, Bal CS. Intracanal medications versus placebo in reducing postoperative endodontic pain \u0026ndash; a double \u0026ndash; blind randomized clinical trial. Braz Dent J. 2013;24(1):25\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eAlonso-Ezpeleta LO, Gasco-Garcia C, Castellanos-Cosano L, Martin-Gonzalez J, Lopez-Frias FJ, Segura-Egea JJ. Postoperative pain after one-visit root-canal treatment on teeth with vital pulps: Comparison of three different obturation techniques. Med Oral Patol Oral Cir Bucal. 2012;e721\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eSj\u0026ouml;gren U, H\u0026auml;gglund B, Sundqvist G, Wing K. Factors affecting the long-term results of endodontic treatment. J Endod. 1990 Oct;16(10):498\u0026ndash;504. \u003c/li\u003e\n\u003cli\u003e\u0026Oslash;rstavik D, Kerekes K, Eriksen HM. The periapical index: A scoring system for radiographic assessment of apical periodontitis. Dental Traumatology. 1986 Feb 27;2(1):20\u0026ndash;34. \u003c/li\u003e\n\u003cli\u003eErdem Hepsenoglu Y, Eyuboglu TF, \u0026Ouml;zcan M. Postoperative Pain Intensity after Single- versus Two-visit Nonsurgical Endodontic Retreatment: A Randomized Clinical Trial. J Endod. 2018 Sep;44(9):1339\u0026ndash;46. \u003c/li\u003e\n\u003cli\u003eKececi A.D., Celik D. Acute exacerbations in endodontics (Flare-up). Acta Odontologica Turcica. 2003;20(1):61\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eFabricius L, Dahl\u0026eacute;n G, Holm SE, M\u0026ouml;ller AJR. Influence of combinations of oral bacteria on periapical tissues of monkeys. Eur J Oral Sci. 1982 Jun;90(3):200\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eFabricious L, Dahlen G, \u0026Ouml;hman AE, M\u0026ouml;ller AJR. Predominant indigenous oral bacteria isolated from infected root canals after varied times of closure. Eur J Oral Sci. 1982 Apr;90(2):134\u0026ndash;44. \u003c/li\u003e\n\u003cli\u003eM\u0026ouml;leer AkeJR, Fabricius L, Dahl\u0026eacute;n G, \u0026Ouml;hman AE, Heyden G. Influence on periapical tissues of indigenous oral bacteria and necrotic pulp tissue in monkeys. Eur J Oral Sci. 1981 Dec;89(6):475\u0026ndash;84. \u003c/li\u003e\n\u003cli\u003eJacinto RC, Gomes BPFA, Ferraz CCR, Zaia AA, Filho FJS. Microbiological analysis of infected root canals from symptomatic and asymptomatic teeth with periapical periodontitis and the antimicrobial susceptibility of some isolated anaerobic bacteria. Oral Microbiol Immunol. 2003 Oct 21;18(5):285\u0026ndash;92. \u003c/li\u003e\n\u003cli\u003eGama TG V., Machado de Oliveira JC, Abad EC, R\u0026ocirc;\u0026ccedil;as IN, Siqueira JF. Postoperative pain following the use of two different intracanal medications. Clin Oral Investig. 2008 Dec 10;12(4):325. \u003c/li\u003e\n\u003cli\u003eBasrani B, Tj\u0026auml;derhane L, Santos JM, Pascon E, Grad H, Lawrence HP, et al. Efficacy of chlorhexidine- and calcium hydroxide\u0026ndash;containing medicaments against Enterococcus faecalis in vitro. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2003 Nov;96(5):618\u0026ndash;24. \u003c/li\u003e\n\u003cli\u003eAslan T, D\u0026ouml;nmez \u0026Ouml;zkan H. The effect of two calcium silicate‐based and one epoxy resin‐based root canal sealer on postoperative pain: a randomized controlled trial. Int Endod J. 2021 Feb 17;54(2):190\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eSch\u0026auml;fer E, Bossmann K. Antimicrobial efficacy of chloroxylenol and chlorhexidine in the treatment of infected root canals. Am J Dent. 2001 Aug;14(4):233\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eNg Y ‐L., Glennon JP, Setchell DJ, Gulabivala K. Prevalence of and factors affecting post‐obturation pain in patients undergoing root canal treatment. Int Endod J. 2004 Jun 25;37(6):381\u0026ndash;91. \u003c/li\u003e\n\u003cli\u003eJabeen S, Khurshiduzzaman M. Incidence of post obturation pain following single and multi visit root canal treatment in a teaching hospital of Bangladesh. Mymensingh Med J. 2014 Apr;23(2):254\u0026ndash;60. \u003c/li\u003e\n\u003cli\u003eMorse DR, Esposito J V. A clarification on endodontic flare-ups. Oral Surgery, Oral Medicine, Oral Pathology. 1990 Sep;70(3):345\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eGarcia-Font M, Dur\u0026aacute;n-Sindreu F, Morell\u0026oacute; S, Irazusta S, Abella F, Roig M, et al. Postoperative pain after removal of gutta-percha from root canals in endodontic retreatment using rotary or reciprocating instruments: a prospective clinical study. Clin Oral Investig. 2018 Sep 2;22(7):2623\u0026ndash;31. \u003c/li\u003e\n\u003cli\u003eGlennon JP, Ng Y ‐L., Setchell DJ, Gulabivala K. Prevalence of and factors affecting postpreparation pain in patients undergoing two‐visit root canal treatment. Int Endod J. 2004 Jan 13;37(1):29\u0026ndash;37. \u003c/li\u003e\n\u003cli\u003eYaylali IE, Teke A, Tunca YM. The Effect of Foraminal Enlargement of Necrotic Teeth with a Continuous Rotary System on Postoperative Pain: A Randomized Controlled Trial. J Endod. 2017 Mar;43(3):359\u0026ndash;63. \u003c/li\u003e\n\u003cli\u003eSingh RD, Khatter R, Bal RK, Bal CS. Intracanal medications versus placebo in reducing postoperative endodontic pain \u0026ndash; a double \u0026ndash; blind randomized clinical trial. Braz Dent J. 2013;24(1):25\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eGomes BPFA, Aveiro E, Kishen A. Irrigants and irrigation activation systems in Endodontics. Braz Dent J. 2023 Aug;34(4):1\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eYoldas O, Topuz A, Is\u0026ccedil;i AS, Oztunc H. Postoperative pain after endodontic retreatment: Single- versus two-visit treatment. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2004 Oct;98(4):483\u0026ndash;7. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"clinical-oral-investigations","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cloi","sideBox":"Learn more about [Clinical Oral Investigations](http://link.springer.com/journal/784)","snPcode":"784","submissionUrl":"https://submission.nature.com/new-submission/784/3","title":"Clinical Oral Investigations","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"calcium hydroxide, chlorhexidine gel, endodontic postoperative pain, flare-up, intracanal medicament","lastPublishedDoi":"10.21203/rs.3.rs-4090764/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4090764/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eThis randomized clinical trial aimed to compare the effect of intracanal medicaments on the incidence of postoperative pain and flare-up with posttreatment apical periodontitis (PTAP) of retreatment cases.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003eOne hundred-twenty patients diagnosed with PTAP with single-rooted teeth with single-canal without spontaneous pain or swellings were included and randomly divided into three groups according to the intracanal medicament used. Intracanal medicaments were placed into the root canals following the removal of previous root canal fillings and re-instrumentation. Calcium hydroxide (Ca (OH)\u003csub\u003e2\u003c/sub\u003e), chlorhexidine gel (CHX), calcium hydroxide and chlorhexidine gel combinations were used as intracanal medicaments. Postoperative pain scores were recorded at 6 and 12 hours and at 1, 2, 3, 4, 5, 6, and 7 days using visual analog scale (VAS). Sensitivity on percussion, spontaneous pain, swelling, antibiotic and analgesic requirements of the patients were evaluated during clinical examinations performed postoperatively after 2 and 7 days.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThere were no statistically significant differences between groups in terms of VAS scores following the intracanal medicament application (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, compared to the patients belong to 20\u0026ndash;34 and 50\u0026ndash;65 age groups, greater VAS scores was observed in patients between the ages of 35\u0026ndash;49 at 12 hour, and 3, 4, 7 days (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Flare-up was observed in only one patient in CHX gel group, and no flare-up was observed in other groups.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eSimilar postoperative pain incidence in all experimental groups indicates that all three medicaments are clinically acceptable in inter-appointment management of retreatment cases in terms of post endodontic pain and flare-up.\u003c/p\u003e\u003ch2\u003eClinical Relevance:\u003c/h2\u003e \u003cp\u003eIn this randomized clinical trial, three different intracanal medicaments were utilized in nonsurgical endodontic retreatment and their effect on the postoperative pain and flare-up incidance was examined. There are limited number of prospective clinical trials in the literature about this issue. Thus, this study will be significant contribute to the literature.\u003c/p\u003e","manuscriptTitle":"The Incidence and Intensity of Postoperative Pain and Flare-up Following the Use of Three Different Intracanal Medicaments In Teeth With Posttreatment Apical Periodontitis: A Randomized Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-21 18:25:21","doi":"10.21203/rs.3.rs-4090764/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-15T19:59:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-26T09:37:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"43e01f3c-731f-4150-8cb4-8f545e8f2b7c","date":"2024-03-26T07:23:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"f1b5bfb4-a8bd-4066-8a3e-547780904777","date":"2024-03-25T21:28:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-25T18:27:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-19T02:42:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-19T02:42:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Clinical Oral Investigations","date":"2024-03-13T07:56:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"clinical-oral-investigations","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cloi","sideBox":"Learn more about [Clinical Oral Investigations](http://link.springer.com/journal/784)","snPcode":"784","submissionUrl":"https://submission.nature.com/new-submission/784/3","title":"Clinical Oral Investigations","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"69df040b-5a87-405f-9cc1-bc7c6393d669","owner":[],"postedDate":"March 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-06-21T14:47:28+00:00","versionOfRecord":{"articleIdentity":"rs-4090764","link":"https://doi.org/10.1007/s00784-024-05760-w","journal":{"identity":"clinical-oral-investigations","isVorOnly":false,"title":"Clinical Oral Investigations"},"publishedOn":"2024-06-08 14:47:28","publishedOnDateReadable":"June 8th, 2024"},"versionCreatedAt":"2024-03-21 18:25:21","video":"","vorDoi":"10.1007/s00784-024-05760-w","vorDoiUrl":"https://doi.org/10.1007/s00784-024-05760-w","workflowStages":[]},"version":"v1","identity":"rs-4090764","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4090764","identity":"rs-4090764","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}