Fusobacterium nucleatum exacerbates the progression of pulpitis by regulating the STING-dependent pathway.

Bacterial infection is the main cause of pulpitis. However, whether a dominant bacteria can promote the progression of pulpitis and its underlying mechanism remains unclear. We provided a comprehensive assessment of the microbiota alteration in pulpitis using 16S rRNA sequencing. Fusobacterium nucleatum was the most enriched in pulpitis and played a pathogenic role accelerating pulpitis progression in rat pulpitis model. After odontoblast-like cells cocultured with F. nucleatum, the stimulator of interferon genes (STING) pathway and autophagy were activation. There was a float of STING expression during F. nucleatum stimulation. STING was degraded by autophagy at the early stage. At the late stage, F. nucleatum stimulated mitochondrial Reactive Oxygen Species (ROS) production, mitochondrial dysfunction and then mtDNA escape into cytosol. mtDNA, which escaped into cytosol, caused more cytosolic mtDNA binds to cyclic GMP-AMP synthase (cGAS). The release of IFN-ß was dramatically reduced when mtDNA-cGAS-STING pathway inhibited. STING-/- mice showed milder periapical bone loss and lower serum IFN-ß levels compared with wildtype mice after 28 days F. nucleatum-infected pulpitis model establishment. Our data demonstrated that F. nucleatum exacerbated the progression of pulpitis, which was mediated by the STING-dependent pathway.

Inhibiting Nav1.7 channels in pulpitis: An in vivo study on neuronal hyperexcitability.

Pulpitis constitutes a significant challenge in clinical management due to its impact on peripheral nerve tissue and the persistence of chronic pain. Despite its clinical importance, the correlation between neuronal activity and the expression of voltage-gated sodium channel 1.7 (Nav1.7) in the trigeminal ganglion (TG) during pulpitis is less investigated. The aim of this study was to examine the relationship between experimentally induced pulpitis and Nav1.7 expression in the TG and to investigate the potential of selective Nav1.7 modulation to attenuate TG abnormal activity associated with pulpitis. Acute pulpitis was induced at the maxillary molar (M1) using allyl isothiocyanate (AITC). The mice were divided into three groups: control, pulpitis model, and pulpitis model treated with ProTx-II, a selective Nav1.7 channel inhibitor. After three days following the surgery, we conducted a recording and comparative analysis of the neural activity of the TG utilizing in vivo optical imaging. Then immunohistochemistry and Western blot were performed to assess changes in the expression levels of extracellular signal-regulated kinase (ERK), c-Fos, collapsin response mediator protein-2 (CRMP2), and Nav1.7 channels. The optical imaging result showed significant neurological excitation in pulpitis TGs. Nav1.7 expressions exhibited upregulation, accompanied by signaling molecular changes suggestive of inflammation and neuroplasticity. In addition, inhibition of Nav1.7 led to reduced neural activity and subsequent decreases in ERK, c-Fos, and CRMP2 levels. These findings suggest the potential for targeting overexpressed Nav1.7 channels to alleviate pain associated with pulpitis, providing practical pain management strategies.

Osteopontin interacts with dendritic cells and macrophages in pulp inflammation: Comprehensive transcriptomic analysis and laboratory investigations.

AIM: To investigate novel diagnostic markers for pulpitis and validate by clinical samples from normal and inflamed pulp. To explore the relationship between diagnostic markers and immune cells or their phenotypes during pulp inflammation. METHODOLOGY: Two microarray datasets, GSE77459 and GSE92681, and identified differential expression genes were integrated. To understand immune features, gene functions, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) and ImmuneSigDB Gene Set Enrichment Analysis (GSEA) were analysed. For predictive purposes, machine learning techniques were applied to detect diagnostic markers. Immune infiltration in inflamed pulp was studied using CIBERSORT. The relationship between diagnostic markers and immune cells was investigated and validated their gene expression in clinical samples from the normal or inflamed pulp by qRT-PCR. Finally, the correlation between one marker, secreted phosphoprotein 1 (SPP1), encoding osteopontin (OPN), and dendritic cells (DCs)/macrophages was identified via HE staining and multiplex immunohistochemistry. An in vitro inflammatory dental pulp microenvironment model of THP-1 macrophages cocultured with dental pulp cells derived conditioned media (DPCs-CM) to investigate OPN production and macrophage phenotypes was established. RESULTS: Analysis revealed unique immunologic features in inflamed pulp. Three diagnostic markers for pulpitis: endothelin-1 (EDN1), SPP1, and purine nucleoside phosphorylase (PNP), and validated them using qRT-PCR were predicted. Multiplex immunohistochemistry demonstrated OPN co-localized with activated DCs and M2 macrophages during pulp inflammation. In vitro experiments showed that THP-1 macrophages produced the highest levels of OPN when stimulated with DPCs-CM derived from the 20 µg/mL LPS pre-conditioned group, suggesting an M2b-like phenotype by increasing surface marker CD86 and expression of IL6, TNFα, IL10, and CCL1 but not CCL17 and MerTK. Levels of CCL1 and IL10 elevated significantly in the macrophages' supernatant from the 20 µg/mL LPS pre-conditioned CM group. OPN was proven co-localizing with CD86 in the inflamed pulp by immunofluorescence. CONCLUSIONS: The current findings suggest that OPN can serve as a promising biomarker for pulpitis, correlated with DCs and macrophages. OPN+ macrophages in the inflamed pulp are associated with M2b-like phenotypes. These insights offer the potential for improved diagnosis and targeted therapy.

The use of medicaments in the management of symptomatic irreversible pulpitis: A community-based cohort study.

AIM: To investigate patient outcomes from either pulpotomy or pulpectomy for the management of symptomatic irreversible pulpitis, with and without application of antibiotic/corticosteroid pastes in urgent primary dental care settings in the United Kingdom. METHODOLOGY: All patients receiving intervention for symptomatic irreversible pulpitis in three different primary care settings were invited to participate. Pre-operatively, data regarding patients' numerical ratings scale (NRS), pain score (0-10), analgesic use, oral-health impact profile-14 (OHIP-14) and need for time away from work were collected. For 7 days post-operatively, participants recorded their NRS pain score, global rating of change score, medication use and their ability to work. Analysis used a mixed-effects model with post hoc Tukey's multiple comparisons test for continuous data and chi-squared or Fisher's exact test for categorical data. To test the effect of the corticosteroid/antibiotic paste, pulpectomy and pulpotomy groups were combined following Mantel-Haenszel stratified analysis or a weighted average of the difference between pulpotomy and pulpectomy with and without the use of corticosteroid/antibiotic paste. A binary composite score was constructed using pre- and post-operative data, whereby overall treatment success was defined as: (i) patients did not return for treatment due to pain by day seven; (ii) at day three, there was a 33% (or 2-points) reduction in NRS pain score; (iii) there was a change score of +3 in global rating; (iv) the patient was no longer using analgesia and able to return to work. RESULTS: Eighty-five participants were recruited, with 83 completing follow up. Overall treatment success was 57%, with 25% of participants returning for more treatment due to inadequate pain relief. Overall treatment success did not differ between the two groups (p = .645), although patients self-reported greater improvement with an antibiotic/corticosteroid dressing for global rating of change (p = .015). CONCLUSIONS: This study identified limited evidence of improved outcomes using antibiotic/corticosteroid dressings in the management of symptomatic irreversible pulpitis in the emergency setting. Further clinical research is needed to understand if these medications are beneficial in affording pain relief, above that of simple excision of irreversibly inflamed pulp tissue.

Discriminatory performance of the pulpal inflammatory biomarkers; Interleukin-8 and TNF-α in patients with symptoms indicative of reversible and irreversible pulpitis: A diagnostic accuracy study.

AIM: The success of vital pulp treatment (VPT) procedures is dependent on an accurate diagnosis of the pulpal inflammatory condition. Compared with current subjective pulpal diagnostic tests, inflammatory molecular biomarkers involved in the pathogenesis of pulpitis represent potential objective indicators of the degree of pulpal inflammation. Therefore, the aim of this study was to quantify level of inflammatory biomarkers - Interleukin 8 (IL-8) and TNF-α in patients diagnosed with reversible pulpitis (RP), irreversible pulpitis (IR) and normal pulp (NP) and investigate their diagnostic accuracy in differentiating between healthy and inflamed conditions. METHODOLOGY: This prospective, cross-sectional study enrolled 72 patients aged 14-53 years with extremely deep carious lesions after establishing a clinical diagnosis of RP (n = 42), symptomatic IR (n = 22) and NP (n = 8). 50 µL of pulpal blood sample was collected from all the patients using a micropipette after pulpal exposure. The level of IL-8 and TNF-α was assessed in pg/mL using enzyme-linked immunosorbent assays. Mann-Whitney U test was applied to establish the association between IL-8/TNF-α level and degree of pulp inflammation. Receiver operating curve (ROC) analysis was carried out to calculate area under the curve (AUC) for RP versus IR. Cut-off values were established using Youden's index. RESULTS: IL-8 and TNF-α levels differed significantly between RP and IR groups (p ≤ .001). The median value of IL-8 in RP and IP groups was 259.8 pg/mL [187.5-310.0] and 1357.8 pg/mL [1036.7-2177.6] respectively. The AUC-ROC curve for RP versus IR was 0.997 with 95.5% sensitivity and 99.76% specificity. The median value of TNF-α in RP and IR groups was 75.4 pg/mL [62.7-95.8] and 157.6 pg/mL [94.1-347.3]. The AUC-ROC curve for TNF-α was 0.812 with a sensitivity and specificity of 59.1% and 92.1%, respectively. IL-8 and TNF-α levels were below detection levels for all NP samples. CONCLUSION: This study showed that pulpal blood could provide an excellent medium for establishing pulpal diagnosis under extremely deep carious lesions. The selected cytokines, IL-8 and TNF-α, demonstrated excellent discriminatory performance for reversible and irreversible pulpitis. Future studies should correlate the IL-8/TNF-α levels with VPT treatment outcomes.

Inflammatory microenvironment of moderate pulpitis enhances the osteo-/odontogenic potential of dental pulp stem cells by autophagy.

AIM: This study investigated the effects of the inflammatory microenvironment of moderate pulpitis on biological properties of human dental pulp stem cells (DPSCs) and further explored the mechanism involved in osteo-/odontogenic induction of the inflammatory microenvironment. METHODOLOGY: Healthy DPSCs (hDPSCs) and inflammatory DPSCs (iDPSCs) were isolated from human-impacted third molars free of caries and clinically diagnosed with moderate pulpitis, respectively. Healthy DPSCs were treated with lipopolysaccharides (LPS) to mimic iDPSCs in vitro. The surface markers expressed on hDPSCs and iDPSCs were detected by flow cytometry. A CCK-8 assay was performed to determine cell proliferation. Flow cytometric analysis was used to evaluate cell apoptosis. The osteo-/odontogenic differentiation of DPSCs was evaluated by western blot, alkaline phosphatase staining, and Alizarin Red S staining. The functions of the genes of differentially expressed mRNAs of hDPSCs and iDPSCs were analysed using gene set enrichment analysis. Transmission electron microscopy and western blot were used to evaluate the autophagy changes of LPS-treated DPSCs. RESULTS: Compared with hDPSCs, iDPSCs showed no significant difference in proliferative capacity but had stronger osteo-/odontogenic potential. In addition, the mRNAs differentially expressed between iDPSCs and hDPSCs were considerably enriched in autophagosome formation and assembly-related molecules. In vitro mechanism studies further found that low concentrations of LPS could upregulate DPSC autophagy-related protein expression and autophagosome formation and promote its odontogenic/osteogenic differentiation, whereas the inhibition of DPSC autophagy led to the weakening of the odontogenic/osteogenic differentiation induced by LPS. CONCLUSIONS: This explorative study showed that DPSCs isolated from teeth with moderate pulpitis possessed higher osteo-/odontogenic differentiation capacity, and the mechanism involved was related to the inflammatory microenvironment-mediated autophagy of DPSCs. This helps to better understand the repair potential of inflamed dental pulp and provides the biological basis for pulp preservation and hard tissue formation in minimally invasive endodontics.

Effect of preemptive use of a nonsteroidal anti-inflammatory drug and a corticosteroid on the efficacy of inferior alveolar nerve blockade and postoperative pain control in endodontic treatment of molars with symptomatic pulpitis: A randomized double-blind placebo-controlled clinical trial.

AIM: The anaesthetic success rate of an inferior alveolar nerve block (IANB) in mandibular molars with irreversible symptomatic pulpitis can be low, and postoperative pain control in teeth with this diagnosis can be challenging. This study aimed to evaluate the influence of preemptive use of dexamethasone and oral potassium diclofenac on the success of IANB. The influence of these drugs on the intensity of postoperative pain was assessed as a secondary outcome. METHODOLOGY: Eighty-four patients with mandibular molars diagnosed with irreversible symptomatic pulpitis recorded preoperative pain intensity using a cold thermal test and a modified Numerical Rating Scale (mNRS). Sixty minutes before the anaesthetic procedure, patients were randomly assigned to one of three groups based on the medication they received: dexamethasone (4 mg), diclofenac potassium (50 mg), or placebo. All patients received IANB with 4% articaine (1:200 000 epinephrine), and 15 min later, they were evaluated for pain intensity using the cold thermal test. Anaesthetic success was analysed. The pain intensity was then recorded, and endodontic treatment and provisional restoration of the tooth were executed in a single session. Patients were monitored for 6, 12, 24, 48 and 72 h using the mNRS to assess the intensity of postoperative pain. RESULTS: There was a statistically significant increase in anaesthetic success when 4 mg dexamethasone (39.3%) or 50 mg diclofenac potassium (21.4%) was used compared to the placebo group (3.6%) (p < .001), with no significant difference between the two drugs. Regarding postoperative pain, dexamethasone was superior to placebo at 6 h (p < .001), with diclofenac having an intermediate behaviour, not differing between dexamethasone and placebo (p > .05). There was no significant difference amongst the groups at 12 h (p > .05). At 24, 48 and 72 h, the effectiveness of dexamethasone and diclofenac were comparable, and both were superior to placebo (p < .001). CONCLUSION: The use of dexamethasone or diclofenac potassium was favourable in terms of increasing the success rate of inferior alveolar nerve block in cases of mandibular molars with irreversible symptomatic pulpitis and decreased the occurrence of postoperative pain when compared to the use of a placebo.

Ginsenoside Rb1 alleviates lipopolysaccharide-induced inflammation in human dental pulp cells via the PI3K/Akt, NF-κB, and MAPK signalling pathways.

AIM: Among numerous constituents of Panax ginseng, a constituent named Ginsenoside Rb1 (G-Rb1) has been studied to diminish inflammation associated with diseases. This study investigated the anti-inflammatory properties of G-Rb1 on human dental pulp cells (hDPCs) exposed to lipopolysaccharide (LPS) and aimed to determine the underlying molecular mechanisms. METHODOLOGY: The KEGG pathway analysis was performed after RNA sequencing in G-Rb1- and LPS-treated hDPCs. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis were used for the assessment of cell adhesion molecules and inflammatory cytokines. Statistical analysis was performed with one-way ANOVA and the Student-Newman-Keuls test. RESULTS: G-Rb1 did not exhibit any cytotoxicity within the range of concentrations tested. However, it affected the levels of TNF-α, IL-6 and IL-8, as these showed reduced levels with exposure to LPS. Additionally, less mRNA and protein expressions of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were shown. With the presence of G-Rb1, decreased levels of PI3K/Akt, phosphorylated IκBα and p65 were also observed. Furthermore, phosphorylated ERK and JNK by LPS were diminished within 15, 30 and 60 min of G-Rb1 exposure; however, the expression of non-phosphorylated ERK and JNK remained unchanged. CONCLUSIONS: G-Rb1 suppressed the LPS-induced increase of cell adhesion molecules and inflammatory cytokines, while also inhibiting PI3K/Akt, phosphorylation of NF-κB transcription factors, ERK and JNK of MAPK signalling in hDPCs.

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).

Novel cryotherapy technique for pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis- a randomized controlled trial.

OBJECTIVES: To assess the effect of cryotherapy on haemostasis, post-operative pain, and the outcome of full pulpotomy performed in mature permanent teeth with symptomatic irreversible pulpitis. MATERIALS AND METHODS: The study included sixty mature permanent mandibular molar teeth with symptomatic irreversible pulpitis and no periapical rarefaction. After coronal pulp tissue amputation, teeth were randomly allocated to one of two groups (n = 30 each). In group I (conventional pulpotomy), a sterile cotton pellet moistened with 2.5% NaOCl was used for haemostasis. In group II (cryotherapy), the pulp chamber was continuously lavaged with 2.50C normal saline solution for haemostasis using an indigenous portable cryotherapy irrigation unit. Following haemostasis, the pulp was capped with mineral trioxide aggregate and the tooth was restored with resin composite. The time taken to achieve haemostasis was recorded. Preoperative and 24, 48 and 72 h postoperative pain was measured using the Numerical Rating Scale. The pulpotomy outcome was assessed at the 12-month follow-up. Data were analyzed using Fischer's exact test, two-sample t-test, two-sample Wilcoxon rank-sum test, Friedman Test, and Wilcoxon Signed Rank Test. RESULTS: The cryotherapy group achieved haemostasis in less time (p < 0.05). There was a significant pain reduction at 24 and 48 h in the cryotherapy group when compared with the conventional pulpotomy group (P < 0.005). The overall success rate of pulpotomy after 12 months was 88% (n = 22) in both study groups(p < 0.05). CONCLUSIONS: Cryotherapy application reduces postoperative pain and has no adverse effect on the outcome of pulpotomy in permanent teeth with symptomatic irreversible pulpitis. CLINICAL RELEVANCE: The cryotherapy can be incorporated in pulpotomy protocol as an adjunct to minimize post-operative pain.

Occlusal veneer restoration treatment outcomes of cracked tooth syndrome: A 22.4-month follow-up study.

OBJECTIVES: The aims of this clinical study were to investigate success rate, vital pulp survival rate, tooth survival rate and patient-reported masticatory ability by evaluating the pain symptoms and signs of the cracked teeth as well as Index of Eating Difficulty (IED) and Oral Health Impact Profile-14 (OHIP-14) questionnaire after cracked teeth were restored with occlusal veneers. MATERIALS AND METHODS: 27 cracked teeth of 24 patients with cold and/or biting pains without spontaneous/nocturnal pains were recruited in this study. The cracked teeth were restored with occlusal veneers fabricated by lithium disilicate ceramic. Cold test and biting test were used to evaluate pain signs. IED and OHIP-14 questionnaire were used to evaluate masticatory ability. FDI criteria was used to evaluate restorations. The paired Wilcoxon test was used to analyze significant differences of detection rate of pain signs, OHIP scores and IED grade before and after restorations. Kaplan-Meier survival curve was used to describe the success rate, vital pulp survival rate, and tooth survival rate. RESULTS: 27 cracked teeth were restored with occlusal veneers with average of 22.4-month follow-up. Two cracked teeth had pulpitis and pain signs of the other cracked teeth completely disappeared. OHIP total scores were significantly reduced after treatment. Scores of 'pain', 'occlusal discomfort', 'uncomfortable to eat', 'diet unsatisfactory' and 'interrupted meals' reduced significantly after treatment. After treatment, IED grades of 25 vital teeth were significantly lower than those before treatment. FDI scores of 25 restorations except for 2 teeth with pulpitis were no greater than 2. The 12 months accumulated pulp survival rate of the cracked teeth was 92.6%. The 12 months accumulated tooth survival rate was 100%. The success rate at the latest recall was 92.6%. CONCLUSION: Occlusal veneer restorations with success rate of 92.6% and the same pulp survival rate might be an effective restoration for treating the cracked teeth. CLINICAL RELEVANCE: The occlusal veneer restorations might be an option for treating the cracked teeth when cracks only involve enamel and dentin, not dental pulp.

Elective full pulpotomy in mature permanent teeth diagnosed with symptomatic irreversible pulpitis: a two years retrospective study.

AIM: To investigate the outcome of elective full pulpotomy, using calcium silicate-based cements (CSBC), after 2 years, in symptomatic mature permanent teeth with carious lesions, diagnosed as irreversible pulpitis, and analyse the capacity of Wolters et al. (2017) classification to predict the likelihood of treatment failure. METHODS: The treatment records of 56 patients with symptomatic mature teeth with carious lesions, diagnosed as irreversible pulpitis and treated by elective full pulpotomy, using CSBCs as pulp capping materials, were reviewed. Thirteen teeth were excluded. The remaining 43 teeth were evaluated retrospectively at 24 months. Fisher`s exact test with the Lancaster's mid-P adjustment was used to assess different outcomes amongst the diagnostic categories. RESULTS: Four of the cases failed before 24 months and required root canal treatment (RCT). Overall success rate at 2 years was 90.7% (39 of 43). An inverse, but non-significant, correlation was observed between the severity of pulpitis according to the Wolters classification and the treatment success rate (p > 0.05). The type of CSBC used was associated to the success rate (OR = 10.5; 95% C.I. = 0.5 - 207.4; p = 0.027), being 82% with Endosequence and 100% with Biodentine. Postoperative pain associated significantly to lower success rate (66.7%) (Odds ratio = 8.0; 95% C.I. = 0.7 - 95.9; p = 0.047). CONCLUSIONS: Elective full pulpotomy using a CSBC was a successful choice for the treatment of mature permanent teeth with symptoms indicative of irreversible pulpitis. There were no significant differences between the success rate of mild, moderate and severe pulpitis. Postoperative pain could be considered a risk marker for failure of full pulpotomy. The term "irreversible pulpitis" should be re-signified to indicate the need for access to the pulp chamber, rather than an indication for extraction or RCT.

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.

The management of deep carious lesions and the exposed pulp in fully developed and immature teeth with irreversible pulpitis: a questionnaire-based study among Greek dentists.

OBJECTIVES: The study aimed to identify the preferred management techniques used by dentists in Greece for treating deep carious lesions or pulp exposure during the removal of carious tissue in teeth with irreversible pulpitis. Additionally, the study sought to explore how patient-related factors (such as age and symptoms) and operator-related factors (like material choice and the use of antibiotics) influence these management decisions. MATERIALS AND METHODS: The questionnaire, developed by five investigators, was divided into two parts: the first gathered respondent demographics, and the second presented clinical scenarios of deep carious lesions, requesting treatment strategies, materials used, and antibiotic prescription practices. The scenarios described patients with intense spontaneous pain and very deep carious lesions, differentiated by age and tooth development status.Data collection was via Google Drive, with analysis performed using SPSS 28, Chi-square, and Fisher's exact tests, with significance set at p < 0.05. RESULTS: The study polled 453 Greek dentists about their treatment choices, for deep carious lesions in mature and immature teeth with irreversible pulpitis The majority favored root canal treatment for mature teeth, however quite a few opted for partial or cervical pulpotomy. MTA emerged as the preferred capping material, emphasizing its biocompatibility. Hemostasis management varied, with saline and sodium hypochlorite as popular choices. In cases of immature teeth, a shift towards vital pulp therapy was evident, reflecting a preference for preserving healthy pulp to avoid complex procedures. CONCLUSIONS: Challenges identified include varying treatment preferences, the significance of bleeding control in vital pulp therapy, and the limited use of antibiotics for irreversible pulpitis. While the study has limitations, including sample size and potential biases, its findings offer valuable insights into the decision-making processes of Greek dentists. CLINICAL RELEVANCE: Future research and ongoing education within the dental community could contribute to standardizing treatment approaches and optimizing outcomes for patients with deep carious lesions and irreversible pulpitis.

Comparative effectiveness of preemptive administration of ibuprofen and ibuprofen-arginine on the anesthetic success of inferior alveolar nerve block in teeth with symptomatic irreversible pulpitis - A double-blind randomized clinical trial.

OBJECTIVES: This study examined the impact of premedication with ibuprofen and ibuprofen-arginine and the influence of preoperative pain and anxiety on inferior alveolar nerve block (IANB) efficacy in cases of symptomatic irreversible pulpitis. MATERIALS AND METHODS: The study involved 150 SIP patients who were randomly assigned to receive ibuprofen (600 mg), ibuprofen-arginine (1,155 mg), or a placebo 30 min before IANB. Preoperative anxiety and pain levels were assessed using the Modified Dental Anxiety Scale and the Heft-Parker visual scale. IANB efficacy was determined by the absence of or mild pain during the procedure. Statistical analysis included chi-square, z-tests, Analysis of Variance, and Student's t tests. RESULTS: The ibuprofen and ibuprofen-arginine groups exhibited significantly higher IANB success rates (62% and 78%, respectively) compared to the placebo group (34%). However, no significant difference was observed between the ibuprofen and ibuprofen-arginine groups. Patients with successful IANB in the ibuprofen and ibuprofen-arginine groups displayed lower median anxiety scores (8) than those with failed blocks (15) and lower mean preoperative pain scores (118.3). CONCLUSION: In cases of symptomatic irreversible pulpitis the preemptive medication with ibuprofen-arginine effectively increased the efficacy of the inferior alveolar nerve block The inferior alveolar nerve block efficacy was influenced by preoperative anxiety levels and the intensity of pain. CLINICAL RELEVANCE: This research underscores the potential benefits of oral premedication with ibuprofen and ibuprofen-arginine in improving anesthesia outcomes in cases of symptomatic irreversible pulpitis.

Referred pain is associated with greater odontogenic spontaneous pain and a heightened pain sensitivity in patients with symptomatic irreversible pulpitis.

BACKGROUND: Symptomatic irreversible pulpitis often results in heightened reactions to thermal stimuli such as pain evoked by a cold stimulus, and spontaneous odontogenic pain (unprovoked pain). OBJECTIVE: This study primarily compared the clinical manifestations of odontogenic spontaneous pain and pain provoked by cold stimulus specifically focusing on their sensory discriminative characteristics (intensity, duration and quality) between symptomatic irreversible pulpitis patients with and without referred pain. METHODS: Twenty-three patients with symptomatic irreversible pulpitis with referred pain and 12 patients without referred pain were included in this cross-sectional study. The following outcomes were assessed: odontogenic spontaneous pain and its descriptors; pain evoked by cold stimulus and qualitative sensory testing before and after local anaesthesia; referred pain location; use of analgesic medication; complementary anaesthesia efficacy. T-test, chi-squared and McNemar tests were applied to the data (p < .50). RESULTS: Patients with referred pain presented a greater odontogenic pain intensity (p < .05) when considered the average of the last 24 h. These patients also showed higher pain rating and pain descriptors (p < .05). Intensity and duration of the pain evoked by cold stimulus in the non-affected contralateral tooth at baseline were higher for patients with referred pain (p < .05). CONCLUSION: Symptomatic irreversible pulpitis patients with referred pain present greater odontogenic spontaneous pain and a heightened pain sensitivity. Therefore, patients with referred pain seem more complex from a pain severity perspective, supporting the clinical utility of discriminating symptomatic irreversible pulpitis with and without referred pain.

Systemic Antibiotic Use in Acute Irreversible Pulpitis: Evaluating Clinical Practices and Molecular Insights.

This scoping review systematically evaluates the use of systemic antibiotics in treating acute irreversible pulpitis, integrating clinical practice patterns with recent molecular insights. We analyzed clinical evidence on antibiotic prescription trends among dental professionals and examined molecular research advancements in relation to pulpitis. This review is intended to bridge the gap between clinical practice and molecular research, guiding more evidence-based approaches to treating acute irreversible pulpitis. Electronic databases were searched for relevant articles published in English based on the objective of the review. A second search using all identified keywords and index terms was undertaken across all the included databases. In addition, a reference list of identified articles was searched. Studies including original research, systematic reviews, meta-analyses, clinical trials, and observational and retrospective studies, all written in English and published from 2010 onwards, were included, and an analysis of the text words contained in the titles and abstracts of the retrieved papers and of the index terms used to describe the articles was performed. A total of N = 53 articles were selected. Altogether, N = 43 (76.79%) articles were cross-sectional studies, N = 4 (11.11%) were systematic reviews, and N = 3 (5.36%) were guidelines. The most frequent level of evidence was level VI (N = 43 (76.79%). The mean percentage of dentists who prescribed antibiotics to treat acute irreversible pulpitis was 23.89 ± 23.74% (range: 0.05-75.7). Similarly, for specialists, it was 22.41 ± 15.64 (range 2.2-50.4), and the percentage for undergraduates was 17.52 ± 20.59 (range 0-62.6). The significant developments in research models for pulpitis research and the characterisation of biomarkers have led to better management strategies. Concurrently, significant advancements in molecular research provide new understandings of pulpitis, suggesting alternative therapeutic approaches. Although there are guidelines available, increased rates of antibiotic prescription are still prevalent around the globe.

Unveiling Therapeutic Potential: Targeting Fusobacterium nucleatum's Lipopolysaccharide Biosynthesis for Endodontic Infections-An In Silico Screening Study.

Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of F. nucleatum will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance. A stringent screening strategy utilizing physicochemical and pharmacokinetic parameters along with a virtual screening approach identified two compounds, Lomefloxacin and Enoxacin, with good binding affinity towards the early acyltransferases LpxA and LpxD. Lomefloxacin and Enoxacin, members of the fluoroquinolone antibiotic class, exhibit wide-ranging activity against diverse bacterial strains. Nevertheless, their effectiveness in the context of endodontic treatment requires further investigation. This study explored the potential of Lomefloxacin and Enoxacin to manage endodontic infections via computational analysis. Moreover, the compounds identified herein serve as a foundation for devising novel combinatorial libraries with enhanced efficacy for endodontic therapeutic strategies.

Treatment outcomes of pulpotomy versus pulpectomy in vital primary molars diagnosed with symptomatic irreversible pulpitis: protocol for a non-inferiority randomised controlled trial.

BACKGROUND: Pulpectomy continues to be the standard treatment recommendation for management of vital primary molars diagnosed with symptomatic irreversible pulpitis. The recent decade has seen a paradigm shift in the treatment concepts of how vital mature permanent molars diagnosed with irreversible pulpitis can be more conservatively managed using vital pulp therapy techniques like pulpotomy. However, despite emerging evidence indicating similarities between primary and permanent tooth pulp response to dental caries, there is limited research on whether pulpotomy can be similarly used as a definitive treatment modality for vital primary teeth with irreversible pulpitis. This randomised controlled trial (RCT) aims to compare the treatment effectiveness of pulpotomy versus pulpectomy in management of vital primary molars diagnosed with symptomatic irreversible pulpitis over a two-year period. METHODS/DESIGN: This clinical study is a parallel, two-armed, open label, non-inferiority RCT with a 1:1 allocation ratio between the experimental intervention arm (pulpotomy) and the active comparator arm (pulpectomy). Healthy cooperative children, between 4-9 years of age, who have painful primary molars with clinical symptoms typical of irreversible pulpitis will be recruited after obtaining informed consent from their parents/legal guardians. 50 vital primary molars clinically diagnosed with symptomatic irreversible pulpitis will be randomly distributed between the two treatment arms. The primary outcomes that will be assessed are clinical and radiographic success after six-months, one-year and two-years of the trial interventions. The influence of baseline pre-operative variables (age; gender; tooth type; site of caries; pre-operative furcal radiolucency; pre-operative pain intensity) and intra-operative factors (time taken to achieve haemostasis) on treatment outcomes will also be assessed. The secondary outcome evaluated will be the immediate (24 h and 7 d) post-operative pain relief afforded by the two treatment interventions. DISCUSSION: This trial seeks to provide evidence on whether pulpotomy treatment can be no worse than the standard pulpectomy treatment for the management of symptomatic irreversible pulpitis in vital primary molars. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06183203). Registered on 30 January 2024.

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.