Successful Healing of Periapical Pathology with Partial Pulpotomy in a Mature Permanent Molar: A Case Report.

BACKGROUND Vital pulp therapy approaches are preferred over non-surgical root canal treatment, giving the advantage of preserving the vitality of the dental pulp and thus maintaining its benefits. Such approaches can be performed in teeth having normal apical area; however, performing vital pulp therapy approaches in teeth associated with periapical pathology remains controversial. CASE REPORT We present a case of a mature mandibular right first permanent molar tooth in a medically fit 10-year-old female diagnosed as asymptomatic irreversible pulpitis with asymptomatic apical periodontitis with periapical radiolucency having a periapical index (PAI) score of 4. Partial pulpotomy was performed instead of non-surgical root canal treatment due to uncooperativeness of the patient. Biodentine was used as a pulp capping material. The tooth was restored with resin composite permanent restoration. Six months after the procedure, an intraoral periapical radiograph revealed normal bone features with complete periapical pathology healing and development of intact lamina dura around the mesial and distal roots. The tooth responded normal to electric pulp testing (EPT), cold, percussion, and palpation tests. CONCLUSIONS Periapical pathology involvement having large periapical radiolucency exhibiting PAI score 4 in inflamed dental pulp tooth diagnosed as irreversible pulpitis does not necessitate non-surgical root canal treatment. Partial pulpotomy should be considered as an alternative treatment to promote the return dental pulp and periapical tissue to a healthy condition. Considering a similar approach in older patients would be interesting to gain a more comprehensive understanding of its potential as a treatment method.

Post-endodontic pain in curved canals prepared with different rotary instrumentation techniques: A randomized controlled trial.

BACKGROUND: Curved root canals are associated with the highest number of procedural errors during endodontic instrumentation. Recently, numerous rotary instruments have been developed, with both manual and automated mechanisms, to facilitate endodontic treatment and manage the complications related to it. OBJECTIVES: The aim of the study was to assess post-endodontic pain after using the HyFlex® EDM OneFile (HEDM), WaveOne® Gold (WOG) and XP-endo® Shaper (XPS) systems in the preparation of curved canals in patients with asymptomatic irreversible pulpitis. MATERIAL AND METHODS: A total of 45 molars with curved canals and asymptomatic irreversible pulpitis were randomly divided into 3 equal groups based on the instrumentation used: HEDM (group A); WOG (group B); and XPS (group C). All teeth were prepared according to the manufacturers' instructions. Postendodontic pain was assessed using the visual analog scale (VAS) at 6, 12, 18, 24, 48, and 72 h after root canal instrumentation. The data was analyzed using the one-way analysis of variance (ANOVA) and the paired-samples t test with the Bonferroni correction, with a p-value of 0.05 set for statistical significance. RESULTS: The highest levels of post-endodontic pain were recorded at 6 h after treatment. Then, the values gradually decreased until the pain nearly vanished after 72 h. No statistically significant differences were observed in the VAS scores between groups A and B. At the same time, group C showed the lowest VAS scores at all follow-up time points. CONCLUSIONS: The use of the XPS system resulted in the lowest pain scores at all follow-ups. The HEDM and WOG groups showed no differences in the pain scores throughout the whole follow-up period.

Evaluation of Postoperative Pain after Using Dexamethasone Intracanal Rinse in Irreversible Pulpitis.

OBJECTIVE: To evaluate the efficacy of dexamethasone as a final intracanal rinse in relieving postoperative pain of teeth with symptomatic irreversible pulpitis. STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Department of Operative Dentistry, PIMS, Islamabad, Pakistan, from June 2019 to December 2020. METHODOLOGY: Sixty patients aged 18- 50 years diagnosed with symptomatic irreversible pulpitis were selected according to the inclusion criterion. After obtaining informed consent, root canal therapy (RCT) was initiated under rubber dam. Pulpectomy was done followed by canal preparation. The lottery method was utilised for the division of patients. Group A (experimental) received dexamethasone (4mg/ml in 5ml syringe) as a final rinse, while Group B (control group) recalled after 1 week and asked whether their pain had relieved or not as a yes/no question. After data collection teeth were obturated and permanent restoration was placed. Data were analysed using Chi-square test. RESULTS: The efficacy of dexamethasone as a final intracanal rinse was greater than saline 86.67% and 20.0%, respectively (p < 0.05) in relieving postoperative pain in teeth with symptomatic irreversible pulpitis. CONCLUSION: Dexamethasone was proved to be more efficacious than saline in alleviating postoperative pain when used as a final intracanal rinse after canal instrumentation. KEY WORDS: Irreversible pulpitis, Dexamethasone, Postoperative pain, Pulpectomy.

Impact of repeated preheating of bulk-fill resin composite on postoperative hypersensitivity; a randomized controlled clinical trial.

BACKGROUND: This clinical study was conducted aiming to evaluate the impact of repeated preheating of bulk-fill resin composite on postoperative hypersensitivity. METHODS: A total of 105 eligible, consenting adults were recruited. Patients had posterior teeth suffering from proximal decay with no signs of irreversible pulpitis. Patients were prepared for Class II restorations and restored with bulk-fill resin composite. Patients were randomized into three groups of 35 patients according to the number of preheating cycles for the resin composite syringe used; group I: no preheating; control group at room temperature, group II: Resin composite preheated once, and group III: Resin composite preheated ten cycles. Patients were assessed for postoperative dentin hypersensitivity using the visual analogue scale (VAS) at three-time intervals: day one, one week and by the end of one month after restorative treatment. Statistical analysis was performed; ANOVA with a single factor was used to test for significance at a p value ≤ 0.05. For nonparametric data, the Kruskal‒Wallis test was used to compare the three testing groups. Friedman's test was used to study the changes within each group. Dunn's test was used for pairwise comparisons when the Kruskal‒Wallis test or Friedman's test was significant. RESULTS: The scores of the three groups through the three time intervals were almost zero except for the first day where VAS scores were recorded with maximum score of 3 for groups I and II. Groups II and III; there was no statistically significant change in hypersensitivity scores by time with P-values 0.135 and 0.368, respectively. However, for group I there was a significant difference from VAS score recorded on first day and the two following time intervals. CONCLUSION: The repeated preheating cycles of bulk-fill resin composite prior to curing had no adverse effect on the patients regarding postoperative dentin hypersensitivity. This information could be of utmost significance, as the same resin composite syringe can undergo numerous preheating cycles clinically before it is completely consumed with the advantage of improvement on the handling properties. TRIAL REGISTRATION: The protocol of the current study was registered at www. CLINICALTRIALS: gov , with the identification number NCT05289479 on 21/03/2022. All procedures involving human participants were performed in accordance with the ethical standards of the Research Ethics Committee of the Faculty of Dentistry, Minia University, Egypt, under the approval number 73/440 on 11/09/2020.

Expression patterns of mechanosensitive ion channel PIEZOs in irreversible pulpitis.

BACKGROUND: Mechanosensitive ion channel PIEZOs have been widely reported to involve inflammation and pain. This study aimed to clarify expression patterns of PIEZOs and their potential relations to irreversible pulpitis. MATERIALS AND METHODS: Normal pulp tissues (n = 29) from patients with impacted third molars and inflamed pulp tissues (n = 23) from patients with irreversible pulpitis were collected. Pain levels were assessed using a numerical rating scale. PIEZO expressions were measured using real-time PCR and then confirmed using GEO datasets GSE77459, immunoblot, and immunohistochemistry staining. Correlations of PIEZO mRNA expression with inflammatory markers, pain markers, or clinical pain levels were evaluated using Spearman's correlation analysis. Univariate analysis was conducted to analyze PIEZO expressions based on pain description and clinical examinations of cold test, percussion, palpation, and bite test. RESULTS: Compared with normal pulp tissues, mRNA expression levels of PIEZO1 were significantly increased in inflamed pulp tissues, while PIEZO2 was significantly decreased, which was further confirmed in GSE77459 and on a protein and histological level. The positive correlation of the mRNA expression levels between PIEZO1 and inflammatory markers, as well as between PIEZO2 and pain markers, was verified. PIEZO2 expression was also positively correlated with pain levels. Besides, irreversible pulpitis patients who reported continuous pain and who detected a positive response to cold stimulus exhibited a higher expression level of PIEZO2 in the inflamed pulp tissues. By contrast, patients reporting pain duration of more than one week showed a higher expression level of PIEZO1. CONCLUSIONS: This study demonstrated the upregulation of PIEZO1 and the downregulation of PIEZO2 in irreversible pulpitis and revealed the potential relation of PIEZO1 and PIEZO2 to inflammation and pain. These findings suggested that PIEZOs might play critical roles in the progression of irreversible pulpitis and paved the way for further investigations aimed at novel therapies of irreversible pulpitis by targeting PIEZOs.

A retrospective study on iRoot BP Plus full pulpotomy for primary molars with partial irreversible pulpitis.

OBJECTIVES: This study aimed to observe the outcomes of iRoot BP Plus full pulpotomy in primary molars with partial irreversible pulpitis retrospectively. METHODS: Collect 102 cases of primary molars with partial irreversible pulpitis undergoing iRoot BP Plus full pulpotomy from January 2019 to August 2023, with a follow-up period of 24-47 months. Based on the presence of irreversible pulpitis symptoms before surgery, the included cases will be divided into asymptomatic group (n=53) and symptomatic group (n=49). Observe the clinical and imaging success rates of both groups. RESULTS: Clinical success rates were 96.2% and 97.9% in asymptomatic and symptomatic groups, and radiographic success rates were 96.2% and 93.9% respectively. CONCLUSIONS: iRoot BP Plus full pulpotomy can be used for the treatment of primary molars with partial irreversible pulpitis under an enhanced pulpotomy protocol.

Pulpotomy for teeth with irreversible pulpitis in immature permanent teeth: a retrospective case series study.

To evaluate the success of pulpotomy in treating immature permanent teeth with irreversible pulpitis. This case series included patients with irreversible pulpitis admitted to the Department of Oral Medicine at the author's Hospital between 2015 and 2020. The pulpotomies were carried out by clinicians with > 5 years of working experience. The follow-up findings and radiographic images were reviewed by two attending dentists. This study included 49 teeth from 48 children (25 boys and 23 girls). The follow-up was 23.3 ± 6.8 months (from 12 to 40 months). The success rate of pulpotomy was 85.7% (42/49). Pulpotomy failed in seven teeth (14.3%). The treatment success rate for traumatic crown fracture was lower than for dental caries and dens evaginatus (P < 0.001). There were no significant differences in the success rate of the pulp-capping agent, tooth root developmental phase, and pulpotomy method (all P > 0.05). Pulpotomy might be successfully used to treat immature permanent teeth with irreversible pulpitis in young patients mainly caused by caries and a fractured tubercle of dens evaginatus.

Efficacy of articaine anesthesia with needle-free/Comfort-in method and conventional needle injection in dental patients with irreversible pulpitis: a randomized clinical trial.

OBJECTIVE: To assess the anesthetic efficacy of articaine with the needle-free/Comfort-in™ method compared to the conventional needle method. To assess pain during anesthesia application, onset of anesthesia and patient`s self-reported quality of life-related to oral health after the dental emergency appointment. MATERIALS AND METHODS: This parallel, randomized clinical trial was conducted by a single operator/dentist in the state of Maranhao, northeast of Brazil. Included participants were adult dental patients with one molar (maxillary) or premolar (maxillary or mandibular) tooth diagnosed with symptomatic irreversible pulpitis. The primary outcome was the anesthetic efficacy, measured using a combination of electrical and cold pulp tests (cold + EPT) and the Numerical Rating Scale (NRS). Secondary outcomes were pain during anesthesia application, onset of anesthesia, and patient`s quality-of-life (measured with the OHIP-14). RESULTS: 62 patients were randomized in the anesthesia needle-free group and Comfort-in group (34.26 ± 10.786 × 33.29 ± 8.399 years old, respectively). The group of patients in the Comfort-in group had 71.0% success. Patients from the Comfort-in group reported statistically lower pain during the anesthesia application than patients from the conventional group (2.13 ± 2.172 × 6.03 ± 3.146 NRS scores, respectively) as well as immediately after the anesthetic procedure. Patients self-reported negative impact in quality of life was similar between groups before (p > 0.05) and after (p > 0.05) the dental emergency. CONCLUSIONS: Comfort-in™ had similar efficacy to the conventional needle method. CLINICAL RELEVANCE: This trial showed that it is possible to anesthetize patients with tooth pulpits without using needles to provide comfort mainly to anxious patients.

TSG-6 Inhibits the NF-κB Signaling Pathway and Promotes the Odontogenic Differentiation of Dental Pulp Stem Cells via CD44 in an Inflammatory Environment.

In pulpitis, dentinal restorative processes are considerably associated with undifferentiated mesenchymal cells in the pulp. This study aimed to investigate strategies to improve the odonto/osteogenic differentiation of dental pulp stem cells (DPSCs) in an inflammatory environment. After pretreatment of DPSCs with 20 ng/mL tumor necrosis factor-induced protein-6 (TSG-6), DPSCs were cultured in an inflammation-inducing solution. Real-time polymerase chain reaction and Western blotting were performed to measure the expression levels of nuclear factor kappa B (NF-κB) and odonto/osteogenic differentiation markers, respectively. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to assess cell proliferation and activity. Subcutaneous ectopic osteogenesis and mandibular bone cultures were performed to assess the effects of TSG-6 in vivo. The expression levels of odonto/osteogenic markers were higher in TSG-6-pre-treated DPSCs than nontreated DPSCs, whereas NF-κB-related proteins were lower after the induction of inflammation. An anti-CD44 antibody counteracted the rescue effect of TSG-6 on DPSC activity and mineralization in an inflammatory environment. Exogenous administration of TSG-6 enhanced the anti-inflammatory properties of DPSCs and partially restored their mineralization function by inhibiting NF-κB signaling. The mechanism of action of TSG-6 was attributed to its interaction with CD44. These findings reveal novel mechanisms by which DPSCs counter inflammation and provide a basis for the treatment of pulpitis.

The purinergic receptor P2X3 promotes facial pain by activating neurons and cytokines in the trigeminal ganglion.

The mechanism underlying allodynia/hyperalgesia caused by dental pulpitis has remained enigmatic. This investigation endeavored to characterize the influence of the purinergic receptor P2X3 on pain caused by experimental pulpitis and the mechanism involved. An experimental model of irreversible pulpitis was produced by the drilling and exposure of the dental pulp of the left upper first and second molars in rats, followed by measuring nociceptive responses in the oral and maxillofacial regions. Subsequently, neuronal activity and the expression of P2X3 and pertinent cytokines in the trigeminal ganglion (TG) were meticulously examined and analyzed. Histological evidence corroborated that significant pulpitis was produced in this model, which led to a distinct escalation in nociceptive responses in rats. The activation of neurons, coupled with the upregulated expression of c-fos, P2X3, p-p38, TNF-α and IL-1ß, was identified subsequent to the pulpitis surgery within the TG. The selective inhibition of P2X3 with A-317491 effectively restrained the abnormal allodynia/hyperalgesia following the pulpitis surgery and concurrently inhibited the upregulation of p-p38, TNF-α and IL-1ß within the TG. These findings suggest that the P2X3 signaling pathway plays a pivotal role in instigating and perpetuating pain subsequent to the induction of pulpitis in rats, implicating its association with the p38 MAPK signaling pathway and inflammatory factors.

Efficacy of pulpotomy in managing irreversible pulpitis in mature permanent teeth: A systematic review and meta-analysis.

OBJECTIVES: This paper evaluated the success rates of pulpotomy, compared its efficacy with non-surgical root canal treatment (NSRCT), evaluated different pulpotomy techniques, and analyzed the effectiveness of contemporary bioactive materials in managing irreversible pulpitis in mature permanent teeth. DATA SOURCES: A comprehensive literature search was conducted across multiple databases including PubMed, Web of Science, Scopus, and the Cochrane Library. Search was conducted from the inception of each database to the present, adhering to PRISMA 2020 guidelines. STUDY SELECTION: Studies were selected through a multi-step screening process, focusing on adult populations, randomized controlled trials, and single-arm trials. DATA: Fifteen randomized controlled trials and eight single-arm trials were included. For a follow-up period of more than 24 months, pooled clinical success rate of pulpotomy was 92.9 % (95 %CI;82.1-99.0 %), whereas pooled radiographic success rate was 78.5 % (95 %CI;66.7-88.4 %). Meta-analyses showed that there was no significant difference in success rates between pulpotomy and NSRCT, between full and partial pulpotomy techniques, or between Mineral Trioxide Aggregate pulpotomy and Calcium Enriched Mixture pulpotomy. The results indicated comparable efficacy across these variables. CONCLUSIONS: The study highlights the potential of less invasive treatments. Pulpotomy may be a viable alternative to NSRCT for managing irreversible pulpitis in mature permanent teeth. Limitations such as the low quality of some single-arm trials and the high risk of bias in some randomized controlled trials highlight the need for further research to standardize methodologies and broaden literature inclusion for a more comprehensive understanding of the efficacy of pulpotomy, considering the high success rates reported. Clinical Significance This quantitative systematic review recognizes the potential of full or partial pulpotomy as a viable treatment alternative to root canal therapy for managing irreversible pulpitis in mature permanent teeth. Future studies should aim for standardized protocols to validate these findings and improve patient treatment outcomes.

Interleukin-8 (IL-8) levels in gingival crevicular fluid during root canal treatment of molar teeth with symptomatic irreversible pulpitis: impact of varying sodium hypochlorite concentrations.

BACKGROUND: The aim of this study was to evaluate the effect of the use of different NaOCl concentrations (1%, 2.5%, and 5.25%) during root canal treatment of molar teeth with symptomatic irreversible pulpitis on the change of the IL-8 level in gingival crevicular fluid (GFC). METHODS: GCF sampling was performed on experimental tooth with irreversible pulpitis before and after treatment and also contralateral healthy tooth of 54 patients. The patients were divided into three groups according to concentration of NaOCl solution (n = 18); 1%, 2.5%, and 5.25% NaOCl solution. GCF sampling from experimental teeth was repeated one week after root canal treatment. Statistical analysis was performed using Mann-Whitney U, Wilcoxon test, one-way ANOVA and Pearson correlation analysis. RESULTS: There was a significant correlation between IL-8 levels in GCF samples taken from teeth with pulpitis before treatment and from healthy contralateral teeth (p = .000). Furthermore, the pretreatment IL-8 level was significantly higher than the posttreatment IL-8 level(p < .05). The effect of the NaOCl concentration on the change in IL-8 level betweeen pre and post treatment was not found statistically significant (p > .05). CONCLUSIONS: The use of NaOCl during root canal treatment can effectively reduce the levels of IL-8 in GCF and improve clinical outcomes. TRIAL REGISTRATION: This study was registred in the Institutional Review Board and the Ethics Committee of the University (No:11) on 15/12/2021.

[Research progress in autophagy in the development of pulp inflammation and dental pulp injury reparation and regeneration].

Pulpitis is an infectious disease characterized by persistent inflammation of dental pulp and severe pain of patients, root canal treatment increases the risk of tooth fracture, discoloration and reinfection. Therefore, pulp injury repair and pulp regeneration become the new targets of pulpitis treatment. Autophagy is considered as an important defense and protective mechanism, thus plays an important role in preventing the host from excessive inflammatory reaction. There are few reports on the regulative mechanisms and therapeutic strategies of autophagy on pulp inflammation progression, therefore, this paper reviewed the role of autophagy on the progression of pulpitis, also reviewed the research progress of autophagy on dental pulp injury repair and regeneration, aiming to provide theoretical support for further research and clinical application.

Vital pulp therapy-Factors influencing decision-making for permanent mature teeth with irreversible pulpitis: A systematic review.

BACKGROUND: There is an increased tendency towards adopting minimally invasive interventions in dentistry, supported by advancement in materials and techniques. However, the decision-making process in choosing conservative or invasive treatments is influenced by several factors, particularly in permanent teeth with irreversible pulpitis. OBJECTIVES: The objective of the study was to systematically review the literature regarding factors that influence decision-making for vital pulp therapy (VPT) as definitive treatment option in permanent mature teeth diagnosed with irreversible pulpitis. METHODS: Two independent reviewers searched five electronic databases (PubMed, Embase, Web of Science, Scopus and Cochrane Library). Grey literature was searched through Google Scholar and contact with experts. Defined search keys were applied, and all peer-reviewed literature published with no language nor publication date limits were included. The All studies investigating the factors influencing treatment decision-making in mature permanent teeth with irreversible pulpitis were included. The quality of included studies was assessed by two independent reviewers using the Joanna Briggs Institute quality assessment tool. RESULTS: Six articles were included in the review. All included studies used questionnaires to characterize clinician preferences and attitudes in choosing treatment options for mature permanent teeth with irreversible pulpitis. The available evidence suggests that dentist-related factors have a significant influence on the chosen treatment in teeth with irreversible pulpitis, with speciality training and years of experience influencing the choice of VPT over other treatment options. COVID-19 reportedly swayed the dentists' decision to favour VPT. Only one article studied the influence of patient-related factors, such as age and presence of spontaneous pain on decision-making. Of note, a history of cardiovascular disease moved dentists towards prescribing VPT. DISCUSSION: Collectively, the included studies demonstrated an overriding influence of dentist-related factors on choosing among treatment options for painful teeth diagnosed with irreversible pulpitis. Patient-related factors were acknowledged but there are also potential factors such as socio-economic constraints that were not included in the component studies. CONCLUSION: In teeth with irreversible pulpitis clinicians educational background influence the decision towards a specific treatment option. Further data, preferably derived from clinical records, is necessary in future investigations to explore the effect of other important factors related to both dentists and patients. REGISTRATION: PROSPERO database (CRD42022339653).

Randomized clinical trial of pulpotomy using a premixed injectable calcium silicate cement on mature permanent teeth with reversible pulpitis.

The aim of this two-center randomized controlled trial was to assess the outcomes and relative factors associated with pulpotomies performed using a premixed injectable calcium silicate cement, as compared to mineral trioxide aggregate in mature permanent premolar and molar teeth with reversible pulpitis. Included teeth were randomly divided into two groups according to pulpotomy material (ProRoot MTA [PMTA] group, Endocem MTA Premixed [EPM] group). After pulp exposure, the superficial pulp was either removed to a depth of 2 mm (partial pulpotomy) or completely amputated to the level of the root canal orifice (full pulpotomy). A 3-mm layer of either material was randomly placed over the pulp wound, followed by the application of a thin layer of a light-cured glass ionomer composite liner. The restoration procedure was then carried out during the same visit. After one year of treatment, the pulpotomy success rate was 94.4% (67/71), with no significant difference between the PMTA and EPM groups. The success rate was 93.9% in the PMTA group and 97.1% in the EPM group. There were no significant factors related to the procedures. EPM is a viable alternative to PMTA for single-visit pulpotomies of permanent premolars and molars.

Irreversible pulpitis in mature permanent teeth: a cost-effectiveness analysis of pulpotomy versus root canal treatment.

INTRODUCTION: Evidence-based dentistry suggests pulpotomy as a potential alternative to root canal treatment in mature permanent teeth with irreversible pulpitis. However, the evidence surrounding the cost-valuation and cost-efficacy of this treatment modality is not yet established. In this context, we adopted an economic modeling approach to assess the cost-effectiveness of pulpotomy versus root canal treatment, as this could aid in effective clinical decision-making. METHODS: A Markov model was constructed following a mature permanent tooth with irreversible pulpitis in an 18-year-old patient over a lifetime using TreeAge Pro Healthcare 2022. Transition probabilities were estimated based on existing literature. Costs were estimated based on the United States healthcare following a private-payer perspective and parameter uncertainties were addressed using Monte-Carlo simulations. The model was validated internally by sensitivity analyses, and face validation was performed by an experienced endodontist and health economist. RESULTS: In the base case scenario, root canal treatment was associated with additional health benefit but at an increased cost (1.08 more years with an incremental cost of 311.20 USD) over a period of an individual's lifetime. The probabilistic sensitivity analysis revealed pulpotomy to be cost-effective at lower Willingness-To-Pay (WTP) values (99.9% acceptable at 50 USD) whereas increasing the values of WTP threshold root canal treatment was a cost-effective treatment (99.9% acceptable at 550 USD). CONCLUSION: Based on current evidence, pulpotomy was a cost-effective treatment option at lower WTP values for the management of irreversible pulpitis in mature permanent teeth. However, by increasing the WTP threshold, root canal treatment became a more cost-effective treatment option over a period of lifetime of an individual.

Role of macrophages in trigeminal ganglia in ectopic orofacial pain associated with pulpitis.

OBJECTIVES: This study aimed to elucidate the role of macrophages in the trigeminal ganglia (TG) in developing pulpitis-associated ectopic orofacial pain. METHODS: Rats underwent maxillary pulp exposure, and Fluoro-Gold (FG) was administered in the ipsilateral whisker pad (WP). Head withdrawal threshold (HWT) upon mechanical stimulation of the WP was recorded, and liposomal clodronate clophosome-A (LCCA; macrophage depletion agent) was administered to the TG at three and four days after pulp exposure. Immunohistochemically, TG sections were stained with anti-Iba1 (a macrophage marker) and anti-Nav1.7 antibodies. RESULTS: Pulp exposure decreased HWT and increased the number of Iba1-IR cells near FG-labelled TG neurons. LCCA inhibited the decrease in HWT and stopped the increase of FG-labelled Nav1.7-IR TG neurons in the pulpitis group. CONCLUSIONS: Activation of macrophages by pulpitis induces the overexpression of Nav1.7 in TG neurons receiving inputs from WP, resulting in pulpitis-induced ectopic facial mechanical allodynia.

Acute pulpitis promotes purinergic signaling to induce pain in rats via P38MAPK/NF-κB signaling pathway.

Toothache is one of the most common types of pain, but the mechanisms underlying pulpitis-induced pain remain unknown. The ionotropic purinergic receptor family (P2X) is reported to mediate nociception in the nervous system. This study aims to investigate the involvement of P2X3 in the sensitisation of the trigeminal ganglion (TG) and the inflammation caused by acute pulpitis. An acute tooth inflammation model was established by applying LPS to the pulp of SD rats. We found that the increased expression of P2X3 was induced by acute pulpitis. A selective P2X3 inhibitor (A-317491) reduced pain-like behavior in the maxillofacial region of rats and depressed the activation of neurons in the trigeminal ganglion induced by pulpitis. The upregulated MAPK signaling (p-p38, p-ERK1/2) expression in the ipsilateral TG induced by pulpitis could also be depressed by the application of the P2X3 inhibitor. Furthermore, the expression of markers of inflammatory processes, such as NF-κB, TNF-α and IL-1ß, could be induced by acute pulpitis and deduced by the intraperitoneal injection of P2X3 antagonists. Our findings demonstrate that purinergic P2X3 receptor signaling in TG neurons contributes to pulpitis-induced pain in rats and that P2X3 signaling may be a potential therapeutic target for tooth pain.

Luteolin Is a Potential Immunomodulating Natural Compound against Pulpal Inflammation.

Aim: The present study evaluated the therapeutic effects of luteolin in alleviating pulpitis of dental pulp- (DP-) derived microvesicles (MVs) via the inhibition of protein kinase R- (PKR-) mediated inflammation. Methodology. Proteomic analysis of immortalized human dental pulp (DP-1) cell-derived MVs was performed to identify PKR-associated molecules. The effect of luteolin on PKR phosphorylation in DP-1 cells and the expression of tumor necrosis factor-α (TNF-α) in THP-1 macrophage-like cells were validated. The effect of luteolin on cell proliferation was compared with that of chemical PKR inhibitors (C16 and 2-AP) and the unique commercially available sedative guaiacol-parachlorophenol. In the dog experimental pulpitis model, the pulps were treated with (1) saline, (2) guaiacol-parachlorophenol, and (3) luteolin. Sixteen teeth from four dogs were extracted, and the pulp tissues were analyzed using hematoxylin and eosin staining. Immunohistochemical staining was performed to analyze the expression of phosphorylated PKR (pPKR), myeloperoxidase (MPO), and CD68. Experimental endodontic-periodontal complex lesions were established in mouse molar through a silk ligature and simultaneous MV injection. MVs were prepared from DP-1 cells with or without pretreatment with 2-AP or luteolin. A three-dimensional microcomputed tomography analysis was performed on day 7 (n = 6). Periodontal bone resorption volumes were calculated for each group (nonligated-ligated), and the ratio of bone volume to tissue volume was measured. Results: Proteomic analysis identified an endogenous PKR activator, and a protein activator of interferon-induced PKR, also known as PACT, was included in MVs. Luteolin inhibited the expressions of pPKR in DP-1 cells and TNF-α in THP-1 cells with the lowest suppression of cell proliferation. In the dog model of experimental pulpitis, luteolin treatment suppressed the expression of pPKR-, MPO-, and CD68-positive cells in pulp tissues, whereas guaiacol-parachlorophenol treatment caused coagulative necrosis and disruption. In a mouse model of endodontic-periodontal complex lesions, luteolin treatment significantly decreased MV-induced alveolar bone resorption. Conclusion: Luteolin is an effective and safe compound that inhibits PKR activation in DP-derived MVs, enabling pulp preservation.