Advancements and challenges in stem/progenitor cell transplantation for dentin-pulp regeneration: a systematic review of animal studies (part I).

Dentin-pulp regeneration through stem/progenitor cell transplantation represents a promising frontier in regenerative endodontics. This systematic review meticulously evaluates animal studies to investigate the efficacy of stem cell therapy in repairing/regenerating the dentine-pulp complex in mature/immature animal teeth. Employing a comprehensive electronic search of PubMed and Scopus databases up to October 2023, relevant English studies were identified/assessed. Evaluation parameters encompassed radiographic and histological assessments of dentin-pulp complex formation. Outcome measures included pulp-like and dentin-like tissues regeneration, apical healing, dentin thickening, apical closure, and dentinal bridge formation. The risk-of-bias assessment adhered to the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) guidelines. Out of 3250 identified articles, 23 animal experiments were included, categorized into regenerative procedures in mature teeth (n=11), regenerative procedures in immature teeth (n=4), and vital pulp therapy (n=8). Despite the promising potential, the bias in the included studies was high. Notably, Various scaffolds, and growth factors were employed, highlighting the heterogeneity across the studies. Dental pulp stem cells (DPSCs) and bone marrow stem cells, especially specific subfractions, demonstrated notable regenerative potential: hypoxic conditions and extracellular vesicles from preconditioned DPSCs enhanced regeneration, with considerations of cell fate. Donor age impacted regeneration, and challenges persisted in pulpotomy and direct pulp capping. Scaffold and growth factor choices influenced outcomes, underscoring the need for standardized strategies. Despite the promise, clinical viability faces hurdles, necessitating further investigation into adverse effects, optimized scaffolds, and regulatory considerations. This systematic review illuminates the potential of stem cell transplantation for dentin-pulp complex regeneration. The overall evidence quality, influenced by study heterogeneity and biases, underscores the need for cautious interpretation of findings. Future studies should refine methodologies and establish reliable histological parameters for meaningful advancements in dentin-pulp regeneration.

Advancing dentin-pulp regeneration: clinical perspectives and insights from stem/progenitor cell transplantation (part II).

This systematic review evaluates clinical studies investigating regenerative endodontic procedures for mature/immature teeth utilizing stem cell transplantation. An electronic search of Scopus, PubMed, ISI Web Science, and Google Scholar was conducted up to January 2023. Outcome measures encompassed radiographic (periapical lesion, root length, apical foramen width, volume of the regenerated pulp) and clinical (post-operative pain, sensibility test) parameters. Among 3250 identified articles, five clinical studies were selected, comprising two randomized controlled trials (RCTs) for mature/immature teeth, and three case reports/series for mature teeth. Despite the promising potential, the included studies exhibited a notable risk of bias. The diversity in stem cells (e.g., dental pulp stem cells [DPSCs], umbilical cord mesenchymal stem cells [UC-MSCs]), scaffolds (Atecollagen, collagen membrane, platelet-poor plasma [PPP], leukocyte platelet-rich in fibrin [L-PRF]), and growth factors (granulocyte colony-stimulating factor [G-CSF]) emphasized the heterogeneity across interventions. In RCTs, DPSCs application increased root length and reduced apical foramen width in immature teeth, while UC-MSCs transplantation reduced apical lesions in mature teeth. Transplantation of DPSCs aggregates or UC-MSCs/PPP also elicited positive pulp responses and increased blood flow. In case reports/series, DPSCs application in teeth with irreversible pulpitis resulted in mineralization and increased the regenerated pulp' volume. Furthermore, transplantation of DPSCs with G-CSF/atelocollagen or L-PRF/collagen membrane led to positive pulp responses. While underscoring the potential of stem cell transplantation for regenerative endodontics in mature/immature teeth, the overall evidence quality and the limited number of available studies emphasize the need for cautious interpretation of results. Future well-designed clinical studies are essential to validate these findings further.

Managing failed vital pulp therapies in mature permanent teeth in a retrospective cohort study, with success and survival rates of managing protocols.

Despite advancements in vital pulp therapy (VPT), a subset of cases fails to achieve desired outcomes. This study based on a previous large-scale cohort study involving 1257 VPT-treated teeth, aiming to describe the demographic data and clinical characteristics of all failed cases and their management protocols. Clinical records/images of 105 failed cases treated by a single endodontist (2011-2022) were examined, including 10 extracted teeth. Asymptomatic cases with PDL widening received no intervention, while others underwent management protocols, including (selective) RCT and (tampon) re-VPT. These retreatments were assessed for success (defined as radiographic evidence of healing) and survival (characterized by the retention/function of the treated tooth) using Kaplan-Meier analysis. While 51.4% of all initial failures were diagnosed due to symptoms, 48.6% were symptom-free. Notably, failed cases with symptomatic irreversible pulpitis, and apical periodontitis/widened PDL before initial treatment significantly outnumbered asymptomatic cases and normal PDL, respectively (P = 0.001). Moreover, most of the initial failures were observed in teeth with composite resin rather than amalgam restorations (P = 0.002). The success and survival rates for the management protocols were 91.78% and 95.79%, respectively, over an average follow-up period of 36.94 (± 23.30) months. RCT and re-VPT procedures provide successful outcomes for managing unsuccessful VPTs.

Successful Management of a Rare Distant Endodontic Lesion: A Case Report.

The current case report aims to document a rare presentation of a distant odontogenic lesion of a 35-year-old male patient with mild clinical discomfort in the mandibular right first molar; exploring the diagnostic and therapeutic intricacies of an uncommon distant endodontic pathosis ultimately resolved through meticulous nonsurgical retreatment. Despite a normal oral examination, diagnostic radiography revealed a suboptimal root canal treatment and apical lesions surrounding mesial- and distal-root apices; including a distinct radiolucency beneath the apex of the second mandibular molar discovered through panoramic radiography, and confirmed via cone-beam computed tomography. In addition, the computed tomography disclosed a previously unreported and unusually large endodontic lesion that extended toward the mandibular canal; highlighting a necessity for the continued exploration of a unique endodontic presentation. A nonsurgical endodontic retreatment led to a remarkable reduction in the radiolucent lesions within one year; emphasizing the significance of comprehensive diagnostic approaches and individualized treatments.

Outcomes and predictive factors of vital pulp therapy in a large-scale retrospective cohort study over 10 years.

This cohort study evaluated the long-term success/survival of vital pulp therapies (VPTs) after carious pulp exposure in adult teeth. Additionally, factors influencing long-term success were identified. Teeth treated during 2011-2022 in a private clinic were studied with clinical/radiographic follow-ups. Data included patient demographics, tooth specifics, and treatment details. Outcomes were classified as success/failure based on clinical/radiographic findings, with tooth functionality determining the survival rate. Encompassing 1149 patients and 1257 VPT-treated teeth, the average monitoring period was 42.2 months. Overall VPTs' survival and success rates were 99.1% and 91.6%, respectively. Success rates for 768 direct pulp cappings, 217 miniature pulpotomies, and 272 full pulpotomies were 91.9%, 92.6%, and 90.1%, respectively (P > 0.05). Influencing factors included symptomatic irreversible pulpitis (SIP; HR 1.974, 95% CI 1.242-3.137; P = 0.004), radiographic signs of apical periodontitis (AP; HR 2.983, 95% CI 1.961-4.540; P < 0.001), restoration type (HR 2.263, 95%CI 1.423-3.600; P = 0.001), and restoration surfaces (HR 1.401, 95%CI 1.034-1.899; P = 0.030). This study concludes that VPT techniques consistently exhibit high long-term success/survival rates in treating carious pulp exposures. Critical predictors include initial clinical signs of SIP/AP, caries extent, and use of composite restorations.

Challenging the Misnomer of Irreversible Pulpitis and Deliberating the Urgent Need for Reclassification of Pulpal Diseases Based on the Efficacy of Vital Pulp Therapies: An Overview of Systematic Reviews.

Over recent decades, the definition of irreversible pulpitis (IP), as an irrevocable condition of a compromised dental pulp tissue, has forced clinicians towards invasive root canal treatments. However, the current best evidence challenges the alignment between clinical symptoms and the perceived irreversibility of a negotiated dental pulp tissue. In the above-mentioned context, vital pulp therapy (VPT) has emerged as a revolutionary and transformative approach; introducing minimally invasive techniques to sustain pulp vitality in cases of IP. The present paper aimed to rigorously examine the corresponding published systematic reviews to explore the diverse spectrum of VPT modalities and their outcomes in managing IP cases. Besides, the current review seems to have asserted the need to discard the conventional terminology of irreversible pulpitis, based on the effectiveness of VPTs in the achievement of pulp tissue healing within cases clinically diagnosed as IP.

A Scoping Review of Highly Cited Published Articles in the Iranian Endodontic Journal: A Reflection of Trends in Endodontic Research.

Introduction: Highly cited published articles play a critical role in shaping clinical practice, research directions, and advancements in a specific field of science. The current comprehensive scoping review aimed to provide an overview of highly cited articles published in the "Iranian Endodontic Journal" (IEJ), based on the IEJ's H-index (=29); highlighting their key findings and prominent implications in the field of endodontics. Materials and Methods: A systematic search was conducted in Scopus database to identify the top 29 highly cited published articles. The articles were selected based on their citation count (h-index); reflecting their impact and influence within the scientific community. Data extraction was performed to gather relevant information; including authors, titles, publication years, and the main topic(s) of each article. Results: The selected highly cited published articles covered a broad range of endodontic topics; demonstrating the diversity and depth of research in the field. Key findings include significant contributions in vital pulp therapy, antimicrobial agents, root canal disinfection, regenerative techniques, cone-beam computed tomography applications, and intracanal medicaments. The distribution of research areas reflects the importance of evidence-based practice in clinical decision-making and patient care. Conclusions: These highly cited published articles have shown to have substantial impact on the field of endodontics. They have influenced clinical practice, guided research directions, and have improved patient care. The summary of key findings from each topic and the number of articles related to each area can provide readers with valuable insights into the distribution of research areas, and the significance of contributions made by the aforementioned highly cited published articles.

Outcomes of root canal therapy or full pulpotomy using two endodontic biomaterials in mature permanent teeth: a randomized controlled trial.

OBJECTIVE: The concept of minimally invasive endodontics recommends less-invasive vital pulp therapy (VPT) modalities over more aggressive traditional endodontic approaches in mature permanent teeth with carious pulp exposure, including irreversible pulpitis (IP) cases. Consequently, VPT needs to be compared with root canal therapy (RCT) in terms of treatment outcomes. This randomized clinical trial compares the results of full pulpotomy using two calcium-silicate cements, i.e., mineral trioxide aggregate (MTA) and calcium-enriched mixture (CEM) cement, with RCT in mature permanent teeth. MATERIALS AND METHODS: A total of 157 carious pulp exposure cases in two academic centers with/without established IP were selected/included/randomly appointed to three study arms; (i) RCT (n = 51) as the reference treatment, (ii) pulpotomy with ProRoot MTA (PMTA; n = 55), and (iii) pulpotomy with CEM cement (PCEM; n = 51) as two alternative VPT treatments. Two-year clinical/radiographic results were the outcomes of interest. Data were statistically analyzed through the analysis of variance, chi-square, Fisher exact test, and Kruskal-Wallis. RESULTS: At 2-year recall, 147 teeth were examined (6.4% dropout). All molars, except for one, were clinically functional/symptom-free, and there was no statistical difference between the three study arms (p = 0.653). The radiographic success rates in RCT, PMTA, and PCEM arms were 98%, 100%, and 97.9%, respectively, without statistically significant differences (p = 0.544). CONCLUSION: In the management of mature permanent teeth with/without established IP, all experimental groups exhibited equivalent/comparable results. CLINICAL RELEVANCE: Simple VPT using MTA/CEM can be suggested/recommended as a viable advantageous alternative to RCT for the management of carious pulp exposures with/without sign/symptoms of IP.

Dental stem cell banking: Techniques and protocols.

Dental tissue-derived stem cells (DSCs) provide an easy, accessible, relatively noninvasive promising source of adult stem cells (ASCs), which brought encouraging prospective for their clinical applications. DSCs provide a perfect opportunity to apply for a patient's own ASC, which poses a low risk of immune rejection. However, problems associated with the long-term culture of stem cells, including loss of proliferation and differentiation capacities, senescence, genetic instability, and the possibility of microbial contamination, make cell banking necessary. With the rapid development of advanced cryopreservation technology, various international DSC banks have been established for both research and clinical applications around the world. However, few studies have been published that provide step-by-step guidance on DSCs isolation and banking methods. The purpose of this review is to present protocols and technical details for all steps of cryopreserved DSCs, from donor selection, isolation, cryopreservation, to characterization and quality control. Here, the emphasis is on presenting practical principles in accordance with the available valid guidelines.

Effects of antibiotic administration on post-operative endodontic symptoms in patients with pulpal necrosis: A systematic review and meta-analysis.

OBJECTIVES: The current systematic review and meta-analysis aimed to assess the efficacy of prophylactic oral antibiotics in the management of post-operative endodontic symptoms in adults with necrotic pulp. MATERIALS AND METHODS: A systematic search up to April 2020 was performed to find all randomised controlled trials (RTCs) comparing oral antibiotics with placebo to manage post-endodontic symptoms. The outcome measures were post-operative pain, swelling and/or the combined pain and swelling at different follow-ups. Standardised mean differences (SMDs) and 95% confidence intervals (CIs) were estimated using random-effect inverse-variance method. Additional analysis was performed if heterogeneity existed (P < .05). RESULTS: For post-endodontic pain, 8 RCTs (n = 690) were included. Antibiotic prescription had no significant effect on endodontic pain at 6 (SMD = -0.008, 95% CI -0.279 - 0.264, P = .95), 12 (SMD = -0.080, 95% CI -1.39 - 1.23, P = .90), 24 (SMD = -0.044, 95% CI -0.29 - 0.20, P = .72), 48 (SMD = 0.18, 95% CI -0.26 - 0.62, P = .42) and 72 h (SMD= -0.050, 95% CI -0.33 - 0.23, P = .723) post-operatively. For post-endodontic swelling, 4 RCTs (n = 149) were included. Antibiotic prescription had no significant effect on endodontic swelling at 24 (SMD = 0.29, 95% CI -0.72 - 1.32, P = .56), 48 (SMD = -0.23, 95% CI -0.98 - 0.51, P = .54) and 72 hours (SMD= -0.03, 95% CI -1.25 - 1.33, P = .96), post-operatively. For combined pain and swelling, no meta-analysis was performed. CONCLUSION: The administration of prophylactic antibiotics to prevent post-operative endodontic symptoms is not supported by the current evidence.

Postendodontic Pain after Pulpotomy or Root Canal Treatment in Mature Teeth with Carious Pulp Exposure: A Multicenter Randomized Controlled Trial.

This equivalence, randomized, clinical trial aimed to compare the postoperative pain of root canal therapy (RCT) with pulpotomy with mineral trioxide aggregate (PMTA) or calcium-enriched mixture (PCEM) in permanent mature teeth. In seven academic centers, 550 cariously exposed pulps were included and randomly allocated into PMTA (n = 188), PCEM (n = 194), or RCT (n = 168) arms. Preoperative "Pain Intensity" (PI) on Numerical Rating Scale and postoperative PIs until day 7 were recorded. Patients' demographic and pre-/intra-/postoperative factors/conditions were recorded/analysed. The arms were homogeneous in terms of demographics. The mean preoperative PIs were similar (P=0.998), the mean sum PIs recorded during 10 postoperative intervals were comparable (P=0.939), and the trend/changes in pain relief were parallel (P=0.821) in all study arms. The incidences of preoperative moderate-severe pain in RCT, PMTA, and PCEM arms were 56.5%, 55.7%, and 56.7%, which after 24 hours considerably decreased to 13.1%, 10.6%, and 12.9%, respectively (P=0.578). The time span of endodontic procedures was statistically different; RCT = 69.73, PMTA = 35.37, and PCEM = 33.62 minutes (P < 0.001). Patients with greater preoperative pain, symptomatic apical periodontitis, or presence of PDL widening suffered more pain (P=0.002, 0.035, and 0.023, resp.); however, other pre-/intra-/postoperative factors/conditions were comparable. Pulpotomy with MTA/CEM and RCT demonstrate comparable and effective postoperative pain relief.

Comparison of Antibacterial Effects of Photodynamic Therapy, Modified Triple Antibiotic Paste and Calcium Hydroxide on Root Canals Infected With Enterococcus faecalis: An In Vitro Study.

Introduction: A pivotal issue to achieve success in the treatment of the root canal is root canal disinfection. One of the most important bacteria that infect the root canal is Enterococcus faecalis. This study seeks to examine the effectiveness of 3 methods for disinfecting the root canal: photodynamic therapy, modified triple antibiotic paste (MTAP), and calcium hydroxide. Methods: Sixty-two single-rooted extracted anterior teeth were collected. After cleaning and disinfecting the teeth, their crowns were cut at the CEJ point. The root canals were shaped to the working length up to file F3 ProTaper (F1, F2, F3). EDTA 17% and sodium hypochlorite 2.5% were used for 5 minutes to wash and remove the smear layer, and then the apical foramen was sealed using composite. After that, the teeth were sterilized in an autoclave at 121°C for 15 minutes. Then 10 samples were taken randomly as the negative control. The remaining samples were immersed and cultivated in a suspension containing E. faecalis for 21 days. Then the samples were divided into 5 groups: 2 positive control groups, 1 group treated with the antibiotic paste with the concentration of 1 mg/mL, 1 group treated with calcium hydroxide, and 1 group treated with photodynamic therapy. Then, to collect the biofilm, the ProTaper file F4 was used. After that, the microbial suspension was provided and counting the colonies was carried out to compare the groups. Results: The findings indicated that the amount of CFU/mg of MTAP samples, including clindamycin, metronidazole, ciprofloxacin in the concentration of 1 mg/mL and photodynamic therapy and calcium hydroxide was lower than that in the control group. Antibiotic paste cleansed the root canal up to 99.9%. Photodynamic therapy reduced the amount of CFU/mg to 98.8%, and calcium hydroxide reduced the amount of CFU/mg to 94.13%. Conclusion: Using photodynamic therapy causes a reduction in the biofilm and inhibits the growth of the E. faecalis bacterium. In addition, in this study, MTAP with a concentration of 1 mg/mL was used, which expunged the bacteria completely. Meanwhile, calcium hydroxide had the weakest effect of all on the E. faecalis bacterium.

Efficacy of Corticosteroids on Postoperative Endodontic Pain: A Systematic Review and Meta-analysis.

INTRODUCTION: The purpose of this systematic review and meta-analysis was to evaluate the effectiveness of corticosteroids on postoperative endodontic pain and to determine/adjust between-trial heterogeneity using meta-regression analysis. METHODS: A systematic literature search was conducted to identify randomized clinical trials using corticosteroids to manage postoperative endodontic pain in adults. The outcome measure was pain intensity scores at 6, 12, and 24 hours postoperatively. Standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were estimated using the random effect inverse variance method. The level of significance was set at P < .05. Meta-regression analysis was also performed to examine the associations between effect sizes and study-level covariates. RESULTS: Eighteen randomized clinical trials, comprising 1088 patients, were included. Corticosteroids significantly reduced the incidence of postoperative pain in endodontic patients at 6 hours (SMD = -1.03; 95% CI, -1.55 to -0.51; P = .000), 12 hours (SMD = -1.089; 95% CI, -1.71 to -0.46; P = .001), and 24 hours (SMD = -0.957; 95% CI, -1.34 to -0.56; P = .000). Meta-regression analysis showed that the type and dose of drug, performing intention-to-treat analysis, and using rescue medication could significantly influence the effect size at different time points. CONCLUSIONS: Corticosteroids had a postoperative pain-reducing effect in endodontic patients, and the choice of drug regimens could be an important predictor of pain reduction.

Treatment Outcomes of 4 Vital Pulp Therapies in Mature Molars.

INTRODUCTION: Vital pulp therapy (VPT) is a biological approach to minimally invasive endodontics. This randomized clinical trial aimed to evaluate and compare clinical and radiographic success of 4 VPTs (indirect pulp capping [IPC], direct pulp capping [DPC], miniature pulpotomy [MP], and full pulpotomy [FP]) using calcium-enriched mixture cement for deep caries management of mature permanent molars including teeth with clinical signs of irreversible pulpitis and the presence of apical periodontitis. METHODS: Blinded participants (N = 302) were randomly allocated to 4 study arms. Random allocation was disregarded when visible pulp exposures did not happen after complete caries removal and the tooth was transferred to the IPC arm. Pre- and intraoperative data including vitality test results, pulpal/periapical status, and exposure type/location were recorded. Pain was measured using a numeric rating scale before treatment initiation up to 1 week postoperatively. Participants were followed up for 1 year. RESULTS: The groups were homogenous in terms of age, sex, marital status, education, and practitioner; pre- and intraoperative conditions were similar in all arms and did not affect the long-term success. Preoperative pain and apical periodontitis were significantly different among arms (P < .05); however, it was not the case when the IPC group was excluded. After baseline pain adjustment, pain relief was continuous with similar patterns in all treatment groups. The 3- and 12-month success rates of the VPT techniques were comparable in the IPC (98.7% and 100%, respectively), DPC (98.4% and 94.7%, respectively), MP (98.4% and 91.4%, respectively), and FP (93.5% and 95.5%, respectively) arms, respectively (P > .05). CONCLUSIONS: In deep caries management of mature permanent molars, the 4 VPTs were associated with favorable/comparable clinical and radiographic outcomes. The pulpal and periapical status as well as pulpal exposure type/location had no effect on treatment outcomes.

Long-term outcomes of pulpotomy in permanent teeth with irreversible pulpitis: A multi-center randomized controlled trial.

PURPOSE: To compare success rates of full pulpotomy (FP) with two endodontic biomaterials on symptomatic vital teeth with closed apices in the presence of apical periodontitis. METHODS: In this multicenter controlled clinical trial, 412 volunteers met the inclusion criteria; they were all randomly allocated to either FP/ProRoot mineral trioxide aggregate (MTA) or FP/calcium enriched mixture (CEM) group. The subjects were followed up for 2 and 5 years to evaluate and compare the treatment outcomes. Data were analyzed using Chi square test and the multiple binary logistic regression model. RESULTS: Data for a total number of 344 and 304 subjects were available for 2- and 5-year follow-ups. In terms of clinical outcomes, 2- and 5-year success rates of both groups were ≥ 98%, without significant differences. In terms of radiographic outcomes, the 2-year result of FP/MTA was significantly superior to FP/CEM (P= 0.005); however, the 5-year success rates were similar (P= 0.413). Age and preoperative periapical status did not affect the treatment outcomes. CLINICAL SIGNIFICANCE: Both MTA and CEM biomaterials were found to be equally effective pulpotomy agents for mature permanent molars with irreversible pulpitis and associated apical periodontitis in different age groups. The performance of this novel minimally invasive biotechnology may support a paradigm shift towards more biologic/conservative treatments in dentistry worldwide.

Polymeric scaffolds in tissue engineering: a literature review.

The tissue engineering scaffold acts as an extracellular matrix that interacts to the cells prior to forming new tissues. The chemical and structural characteristics of scaffolds are major concerns in fabricating of ideal three-dimensional structure for tissue engineering applications. The polymer scaffolds used for tissue engineering should possess proper architecture and mechanical properties in addition to supporting cell adhesion, proliferation, and differentiation. Much research has been done on the topic of polymeric scaffold properties such as surface topographic features (roughness and hydrophilicity) and scaffold microstructures (pore size, porosity, pore interconnectivity, and pore and fiber architectures) that influence the cell-scaffold interactions. In this review, efforts were given to evaluate the effect of both chemical and structural characteristics of scaffolds on cell behaviors such as adhesion, proliferation, migration, and differentiation. This review would provide the fundamental information which would be beneficial for scaffold design in future. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 431-459, 2017.

Effect of preoperative oral analgesics on pulpal anesthesia in patients with irreversible pulpitis-a systematic review and meta-analysis.

OBJECTIVES: The objectives of this study were to assess the efficacy of preemptive oral administration of single dose of non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on the local anesthetic success in adults with irreversible pulpitis and to find the possible covariates that could predict treatment effect. MATERIALS AND METHODS: A systematic search using electronic databases up to March 2015 was conducted. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated using random and fixed-effect inverse variance method. Subgroup and meta-regression analyses were conducted to assess the potential source of heterogeneity. RESULTS: Results showed that preemptive analgesics are more effective than placebo in increasing anesthetic success (OR = 0.30, CI% 0.24-0.39, p = 0.000) [Q = 55.860 (p = 0.001)]. In the subgroup analysis, administration of NSAIDs as monotherapy, ibuprofen as mono- vs. combination therapy, oxicam type drugs as monotherapy, and acetaminophen as combination therapy were significantly more effective in increasing anesthetic success OR = 0.25, CI% 0.16-0.38, p = 0.00, Q = 40.539 (p = 0.003); OR = 0.44, CI% 0.26-0.75, p = 0.00, Q = 12.833 (p = 0.011); OR = 0.48, CI% 0.30-0.74, p = 0.002, Q = 15.898 (p = 0.14); OR = 0.30, CI% 0.16-0.38, p = 0.001, Q = 7.506 (p = 0.02); OR = 0.10, CI% 0.16 0.38, p = 0.001, Q = 5.075 (p = 0.07), respectively. However, there was no significant difference in increasing anesthetic success between treatment and placebo arms when acetaminophen was administrated alone. In meta-regression analysis, an association between different types of NSAIDs (indomethacin, diclofenac potassium, and oxicam-type drugs) and articaine with treatment effect was observed. CONCLUSIONS: The administration of preemptive analgesics can induce superior intraoperative analgesia for patients with irreversible pulpitis. However, strategies such as co-administration of certain types of analgesics and anesthetic solution might be predictors of treatment effect. Additionally, there was no association between different timing and dosage of analgesics and treatment effect. CLINICAL RELEVANCE: When compared to placebo, preemptive oral analgesics are superior in achieving anesthetic success in inflamed pulp.