rs12411980 single-nucleotide polymorphism related to PRTFDC1 expression is significantly associated with phantom tooth pain.

Phantom tooth pain (PTP) is one type of non-odontogenic neuropathic toothache, which rarely occurs after appropriate pulpectomy or tooth extraction. The cause of PTP is unknown. We investigated pain-related genetic factors that are associated with PTP. Four pain-associated genes, including G protein-coupled receptor 158 (GPR158) and phosphoribosyl transferase domain containing 1 (PRTFDC1), are adjacent to each other on the human genome. Some of these four genes or their genomic region may be related to PTP. We statistically analyzed associations between single-nucleotide polymorphisms (SNPs) in the genomic region and PTP in patients with PTP (PTP group), other orofacial pain (OFP group), and healthy control subjects. We then performed a database search of expression quantitative trait loci (eQTLs). For the seven SNPs that were significantly associated with PTP even after Bonferroni correction, we focused on the rs12411980 tag SNP (P = 9.42 × 10-4). Statistical analyses of the PTP group and healthy subject groups (group labels: NOC and TD) revealed that the rate of the GG genotype of the rs12411980 SNP was significantly higher in the PTP group than in the healthy subject groups (PTP group vs. NOC group: P = 2.92 × 10-4, PTP group vs. TD group: P = 5.46 × 10-4; percentage of GG: 30% in PTP group, 12% in NOC group, 11% in TD group). These results suggest that the GG genotype of the rs12411980 SNP is more susceptible to PTP. The rs2765697 SNP that is in strong linkage disequilibrium with the rs12411980 SNP is an eQTL that is associated with higher PRTFDC1 expression in the minor allele homozygotes in the healthy subject groups of the rs2765697 SNP. Thus, PRTFDC1 expression similarly increases in the minor allele homozygotes (GG genotype) in the healthy subject groups of the rs12411980 SNP, which would lead to greater susceptibility to PTP.

The rs216009 single-nucleotide polymorphism of the CACNA1C gene is associated with phantom tooth pain.

Phantom tooth pain (PTP) is a rare and specific neuropathic pain that occurs after pulpectomy and tooth extraction, but its cause is not understood. We hypothesized that there is a genetic contribution to PTP. The present study focused on the CACNA1C gene, which encodes the α1C subunit of the Cav1.2 L-type Ca2+ channel (LTCC) that has been reported to be associated with neuropathic pain in previous studies. We investigated genetic polymorphisms that contribute to PTP. We statistically examined the association between genetic polymorphisms and PTP vulnerability in 33 patients with PTP and 118 patients without PTP but with pain or dysesthesia in the orofacial region. From within and around the CACNA1C gene, 155 polymorphisms were selected and analyzed for associations with clinical data. We found that the rs216009 single-nucleotide polymorphism (SNP) of the CACNA1C gene in the recessive model was significantly associated with the vulnerability to PTP. Homozygote carriers of the minor C allele of rs216009 had a higher rate of PTP. Nociceptive transmission in neuropathic pain has been reported to involve Ca2+ influx from LTCCs, and the rs216009 polymorphism may be involved in CACNA1C expression, which regulates intracellular Ca2+ levels, leading to the vulnerability to PTP. Furthermore, psychological factors may lead to the development of PTP by modulating the descending pain inhibitory system. Altogether, homozygous C-allele carriers of the rs216009 SNP were more likely to be vulnerable to PTP, possibly through the regulation of intracellular Ca2+ levels and affective pain systems, such as those that mediate fear memory recall.

Single-nucleotide polymorphisms of the SLC17A9 and P2RY12 genes are significantly associated with phantom tooth pain.

Phantom tooth pain (PTP) is a rare and specific neuropathic pain that occurs after pulpectomy and tooth extraction, but its cause is not understood. We hypothesized that there is a genetic contribution to PTP. We focused on solute carrier family 17 member 9 (SLC17A9)/vesicular nucleotide transporter (VNUT) and purinergic receptor P2Y12 (P2RY12), both of which have been associated with neuropathic pain and pain transduction signaling in the trigeminal ganglion in rodents. We sought to corroborate these associations in humans. We investigated gene polymorphisms that contribute to PTP. We statistically examined the association between genetic polymorphisms and PTP vulnerability in 150 patients with orofacial pain, including PTP, and 500 healthy subjects. We found that the rs735055 polymorphism of the SLC17A9 gene and rs3732759 polymorphism of the P2RY12 gene were associated with the development of PTP. Carriers of the minor allele of rs735055 and individuals who were homozygous for the major allele of rs3732759 had a higher rate of PTP. Carriers of the minor allele of rs735055 reportedly had high SLC17A9 mRNA expression in the spinal cord, which may increase the storage and release of adenosine triphosphate. Individuals who were homozygous for the major allele of rs3732759 may have higher P2RY12 expression that is more active in microglia. Therefore, these carriers may be more susceptible to PTP. These results suggest that specific genetic polymorphisms of the SLC17A9 and P2RY12 genes are involved in PTP. This is the first report on genes that are associated with PTP in humans.

Do different orthodontic pliers used in bracket debonding have different effects on pain and sensitivity? A prospective split-mouth study.

OBJECTIVES: The assessment of whether different orthodontic pliers used in bracket debonding have different effects on pain and sensitivity experience. MATERIALS AND METHODS: Thirty-three patients (17 females, 16 males) with metal brackets were included in the study. Compressed air and freshly melted ice water were applied to each tooth (6-6) in upper and lower arch before bracket debonding (T0), just after debonding (T1), and 1 week after debonding (T2). Bracket remover plier (BRP) and Weingart plier (WP) were used to debond brackets. A numeric rating scale (NRS) was used to assess sensitivity for each tooth at T0, T1, and T2. Tooth pain was assessed for each tooth using NRS during bracket debonding. RESULTS: Statistically higher pain scores were found in teeth U4 (upper first premolar) (p = 0.017) and L6 (lower first molar) (p = 0.026) in Weingart plier group. No statistically significant difference was found during debonding in the other teeth between groups. Statistically high sensitivity score was found at T1 time point in tooth U3 (upper canine) by applying air stimulus in Weingart plier group (p = 0.024). There was no statistically significant difference between the sensitivity scores measured at T2 time point by applying air and cold stimuli between groups. CONCLUSIONS: Although the debonding pain scores were statistically significant in two teeth and the sensitivity score in one tooth, there was no clinical significance between the two pliers in terms of pain and sensitivity. CLINICAL RELEVANCE: Both debonding pliers gave clinically similar results in terms of pain and sensitivity.

Functional Coupling between the P2X7 Receptor and Pannexin-1 Channel in Rat Trigeminal Ganglion Neurons.

The ionotropic P2X receptor, P2X7, is believed to regulate and/or generate nociceptive pain, and pain in several neuropathological diseases. Although there is a known relationship between P2X7 receptor activity and pain sensing, its detailed functional properties in trigeminal ganglion (TG) neurons remains unclear. We examined the electrophysiological and pharmacological characteristics of the P2X7 receptor and its functional coupling with other P2X receptors and pannexin-1 (PANX1) channels in primary cultured rat TG neurons, using whole-cell patch-clamp recordings. Application of ATP and Bz-ATP induced long-lasting biphasic inward currents that were more sensitive to extracellular Bz-ATP than ATP, indicating that the current was carried by P2X7 receptors. While the biphasic current densities of the first and second components were increased by Bz-ATP in a concentration dependent manner; current duration was only affected in the second component. These currents were significantly inhibited by P2X7 receptor antagonists, while only the second component was inhibited by P2X1, 3, and 4 receptor antagonists, PANX1 channel inhibitors, and extracellular ATPase. Taken together, our data suggests that autocrine or paracrine signaling via the P2X7-PANX1-P2X receptor/channel complex may play important roles in several pain sensing pathways via long-lasting neuronal activity driven by extracellular high-concentration ATP following tissue damage in the orofacial area.

Persistent dentoalveolar pain disorder: A putative intraoral chronic overlapping pain condition.

Chronic overlapping pain conditions (COPCs) are conditions that share several clinical characteristics and symptomatology, are usually considered idiopathic in nature, and are frequently comorbid. Currently, there are no established inclusion criteria to determine which conditions should be included under this umbrella term despite different systems proposed. Persistent dentoalveolar pain disorder (PDAP), also referred to as atypical odontalgia and thought to be a component of persistent idiopathic facial pain, is a chronic pain condition that manifests as a persistent tooth pain or pain over a dentoalveolar site formerly occupied by a tooth in the absence of detectable pathology during clinical or radiological examination. PDAP is considered idiopathic in nature, and its pathophysiological mechanisms are not fully understood. Our objective was to investigate whether PDAP fits the conceptual paradigm of COPC given its characteristics and commonalities with other COPC, based on published literature identified through a scoping review. We found that PDAP fits 16 out of 18 common characteristics among COPCs, and based on this finding, we discuss the implications of PDAP being considered a COPC.

Impact of clear aligner therapy on tooth pain and masticatory muscle soreness.

BACKGROUND: Clinical findings suggest that orthodontic treatment with clear aligners (clear aligner therapy/CAT) may cause masticatory muscle soreness in some patients. OBJECTIVE: This multi-site prospective study investigated tooth pain and masticatory muscle soreness and tenderness in patients undergoing CAT and explored whether psychological traits affected these outcomes. METHODS: Twenty-seven adults (22F, 5M; mean age ± SD=35.3 ± 17.6 years) about to start CAT were recruited at three clinics. During CAT, they reported on 100-mm visual analogue scales their tooth pain, masticatory muscle soreness and stress three times per day over 4 weeks (week 1 = baseline; week 2 = dummy aligner; week 3 = first active aligner; week 4 = second active aligner). Pressure pain thresholds (PPTs) were measured at the masseter and temporalis at baseline and after week 4. Mixed models were used to evaluate the outcome measures over time. RESULTS: Clear aligner therapy caused mild tooth pain, which was greater with the passive than the first and second active aligners (both P < .001). Mild and clinically not relevant masticatory muscle soreness was produced by all aligners (all P < .05), with the first active aligner producing less soreness than the dummy aligner (P < .001). PPTs did not change significantly after 4 weeks. Both tooth pain and masticatory muscle soreness were affected by stress and trait anxiety, whilst muscle soreness was affected also by oral behaviours. CONCLUSIONS: In the short term, CAT produces tooth pain and masticatory muscle soreness of limited significance. Frequent oral behaviours are related to increased masticatory muscle soreness during CAT. The medium- and long-term effects of CAT should be further explored.

Ion Channels of Nociception.

The special issue "Ion Channels of Nociception" contains 13 articles published by 73 authors from different countries united by the main focusing on the peripheral mechanisms of pain. The content covers the mechanisms of neuropathic, inflammatory, and dental pain as well as pain in migraine and diabetes, nociceptive roles of P2X3, ASIC, Piezo and TRP channels, pain control through GPCRs and pharmacological agents and non-pharmacological treatment with electroacupuncture.

Ion Channels Involved in Tooth Pain.

The tooth has an unusual sensory system that converts external stimuli predominantly into pain, yet its sensory afferents in teeth demonstrate cytochemical properties of non-nociceptive neurons. This review summarizes the recent knowledge underlying this paradoxical nociception, with a focus on the ion channels involved in tooth pain. The expression of temperature-sensitive ion channels has been extensively investigated because thermal stimulation often evokes tooth pain. However, temperature-sensitive ion channels cannot explain the sudden intense tooth pain evoked by innocuous temperatures or light air puffs, leading to the hydrodynamic theory emphasizing the microfluidic movement within the dentinal tubules for detection by mechanosensitive ion channels. Several mechanosensitive ion channels expressed in dental sensory systems have been suggested as key players in the hydrodynamic theory, and TRPM7, which is abundant in the odontoblasts, and recently discovered PIEZO receptors are promising candidates. Several ligand-gated ion channels and voltage-gated ion channels expressed in dental primary afferent neurons have been discussed in relation to their potential contribution to tooth pain. In addition, in recent years, there has been growing interest in the potential sensory role of odontoblasts; thus, the expression of ion channels in odontoblasts and their potential relation to tooth pain is also reviewed.

Dentin hypersensitivity-like tooth pain seen in patients receiving steroid therapy: An exploratory study.

To ascertain whether steroid therapy evokes dentin hypersensitivity (DH)-like tooth pain, we performed a study based on compelling evidence from patients receiving steroid therapy. An exploratory study was conducted using a questionnaire for 220 patients prescribed steroids who attended the Department of Hematology and Rheumatology of Tohoku University Hospital. Group comparisons between patients with and without steroid pulse therapy were analysed by statistical means. In this study, any DH-like tooth pain that commenced subsequent to steroid treatment was defined as steroid-derived (SD) tooth pain. The prevalence of SD tooth pain was 17.7% (39/220 patients). SD tooth pain was triggered in many vital teeth by cold and/or hot water (84.2% and 23.7%, respectively) with the pain characterised as continuous, in contrast to typical DH tooth pain. SD tooth pain was significantly more frequent in pulse therapy patients than in non-pulse therapy patients (p < 0.05). Logistic regression analysis adjusted for age and sex showed similar results (odds ratio = 3.74, p = 0.013). Moreover, a positive correlation was observed between the steroid dose and pain score (ρ = 0.642). Dose reduction or discontinuation of steroid therapy relieved SD tooth pain in all cases. Thus, steroid therapy can evoke DH-like tooth pain during treatment.

A randomized placebo-blind study of the effect of low power laser on pain caused by irreversible pulpitis.

This randomized placebo-blind study aimed to evaluate the effect of laser phototherapy (LPT) on pain caused by symptomatic irreversible pulpitis (SIP). Sixty patients diagnosed with SIP were randomly assigned to treatment groups (n = 15): G1 (control), G2 (laser placebo-sham irradiation), G3 (laser irradiation at 780 nm, 40 mW, 4 J/cm2), and G4 (laser irradiation at 780 nm, 40 mW, 40 J/cm2). Spontaneous pain was recorded using a VAS score before (T0), immediately after (T1), and 15 min after treatment (T2). Local anesthetics failure during emergency endodontic treatment was also assessed. There was no pain difference in T1 and T2 between the experimental laser groups (G3 and G4) and the placebo group (G2). The 4-J/cm2 (G3) irradiation resulted in significant increase in the local anesthetics failure in lower jar teeth. This effect could be suggested as consequence of the LPT improvement in local circulation and vasodilatation that would result in the increase of local anesthetic agent absorption. The application of 780-nm diode laser irradiation, at 4 and 40 J/cm2, showed no effect in reducing the pain in SIP in comparison to the placebo group. The fluence of 4 J/cm2 showed a negative effect in local anesthetics, resulting in significant increase of complimentary local anesthesia during emergency endodontic treatment. This work provides evidence of the consequence of LPT application on teeth with symptomatic irreversible pulpitis. LPT should be avoided in teeth with pain due to irreversible pulpitis.

The tooth, the whole tooth, and nothing but the tooth: can dental pain ever be the sole presenting symptom of a myocardial infarction? A systematic review.

BACKGROUND: Pain symptoms related to cardiac ischemia can vary greatly from patient to patient. However, should emergency physicians consider the possibility of myocardial infarction in patients who present solely with dental pain? OBJECTIVE: This is a systematic review of the literature investigating the incidence of jaw, tooth, or facial pain as the sole symptom of cardiac ischemia. METHODS: Studies investigating jaw, tooth, or facial pain of cardiac origin were identified using the PubMed database. All English studies in which cardiac pain originated in the face, teeth, or jaw were screened for inclusion. Data were abstracted from each study utilizing a structured review process, and rated for methodological quality. RESULTS: Eighteen studies met study criteria: 16 were case reports, and the remaining 2 were prospective cohort studies. After quality assessment and categorization, nine reports were categorized as weak, eight moderate, and one strong methodological quality. CONCLUSION: Cardiac ischemia may present in no anatomic location other than face or jaw. However, despite frequent claims in the literature to the contrary, the lack of methodological quality of the studies investigated impedes a firm conclusion of face, jaw, or tooth pain as the only symptom of cardiac insufficiency.

Oral pre-trigeminal neuralgia pain: clinical differential diagnosis and descriptive study results.

AIMS: To better quantify oral pre-trigeminal neuralgia (PTN) symptoms, attempt to identify PTN symptoms that could reliably differentiate between PTN and odontogenic tooth pain, and determine whether an anesthetic test would reliably differentiate these disorders. METHODOLOGY: This was accomplished through a survey of symptom recall for 49 trigeminal neuralgia patients who had PTN tooth and/or gum pain. RESULTS: The variability of oral PTN symptoms, factors that worsened or improved them, and how dental anesthesia affected them, explain the reason for variations found in the literature. A throbbing pain quality is not in the literature, but present for 63% of respondents. CONCLUSIONS: No specific PTN symptom would reliably differentiate PTN from odontogenic tooth pain. The results also suggest that an anesthetic test would not be totally reliable for differentiating these disorders. A protocol is provided that should help practitioners identify the tooth pain source when there is no dental pathology.

The anatomy, neurophysiology, and cellular mechanisms of intradental sensation.

Somatosensory innervation of the oral cavity enables the detection of a range of environmental stimuli including minute and noxious mechanical forces. The trigeminal sensory neurons underlie sensation originating from the tooth. Prior work has provided important physiological and molecular characterization of dental pulp sensory innervation. Clinical dental experiences have informed our conception of the consequence of activating these neurons. However, the biological role of sensory innervation within the tooth is yet to be defined. Recent transcriptomic data, combined with mouse genetic tools, have the capacity to provide important cell-type resolution for the physiological and behavioral function of pulp-innervating sensory neurons. Importantly, these tools can be applied to determine the neuronal origin of acute dental pain that coincides with tooth damage as well as pain stemming from tissue inflammation (i.e., pulpitis) toward developing treatment strategies aimed at relieving these distinct forms of pain.

Relationships among barodontalgia prevalence, altitude, stress, dental care frequency, and barodontalgia awareness: a survey of Turkish pilots.

Background: Gas expansion in body cavities due to pressure changes at high altitudes can cause barodontalgia. This condition may compromise flight safety. Aim: To investigate relationships among barodontalgia awareness, dental visit frequency, and barodontalgia prevalence in civilian and military pilots operating at high altitudes. Materials and Methods: Civilian pilots from Turkish Airlines and military pilots from the Turkish Air Force, flying between November 2022 and January 2023, participated in this study. A 20-question survey was administered to 750 pilots, covering topics such as barodontalgia awareness, dental visit frequency, breaks after dental treatments, in-flight pain, and pain type and severity. The voluntary surveys were distributed by email. Results: Of the 750 pilots, 526 completed the survey; 61% were aware of barodontalgia, and 81% of pilots who had experienced it reported pain at altitudes <2000 feet. The study revealed higher barodontalgia awareness among pilots who had experienced it, with the highest prevalence among jet pilots. Pilots with barodontalgia also showed a higher frequency of dental visits (p < 0.001). Additionally, this group reported more frequent interruption of flight due to dental treatment (IFDT), more problems experienced in flights after treatment (PFAT), and higher instances of bruxism or teeth clenching during flight, suggesting stress and anxiety (p < 0.05). Conclusions: Barodontalgia, a type of pain linked to stress, significantly impacts pilot performance, and can threaten flight safety, even at lower altitudes. Thus, there is a need to educate pilots about stress management, barodontalgia awareness, and the importance of regular dental check-ups.

A Patient with Refractory Trigeminal Neuralgia was Referred for Suspected Odontogenic Pain.

Chronic pain of the face with a sudden, unilateral, and electric shock-like pain in the distribution of the trigeminal nerve is known as Trigeminal neuralgia (TN). This case report presents a patient with TN symptoms, along with concomitant tooth pain. The diagnostic process and management of the patient are discussed, emphasizing the importance of interdisciplinary collaboration for optimal patient care.

Bite force of patients with tooth pain.

OBJECTIVES: The aim of this study was twofold: (i) to measure the bite force of healthy adults and patients with tooth pain and (ii) to evaluate the influence of bite force and age on tooth pain and both genders. It is hypothesized that patients with tooth pain would have lesser bite forces as compared to healthy individuals. MATERIAL AND METHODS: Two groups of participants were, the first group comprised 18 healthy adults (9 males, 9 females), while the second group comprised 18 patients with tooth pain (9 males, 9 females), recruited from the Faculty of Dentistry, Universiti Teknologi MARA. Their maximum bite forces were recorded using the Prescale system that consists of pressure-sensitive films and a precalibrated scanning device. Logistic regression models were used using bite force and age on dichotomous responses of tooth pain status and gender. RESULTS: The mean bite force of patients with tooth pain was 684.77 ± 501.13 N, which was lesser than 798.33 ± 492.16 N of the healthy adults. The reduced gender logistic regression model on gender with age was found to be statistically significant (p ≤ .05). CONCLUSIONS: Even though the mean bite force was smaller in the group with dental pain, this difference was not statistically significant.

Periodontal acidification contributes to tooth pain hypersensitivity during orthodontic tooth movement.

Tooth movements associated with orthodontic treatment often cause tooth pain. However, the detailed mechanism remains unclear. Here, we examined the involvement of periodontal acidification caused by tooth movement in mechanical tooth pain hypersensitivity. Elastics were inserted between the first and second molars to move the teeth in Sprague-Dawley rats. Mechanical head-withdrawal reflex threshold to first molar stimulation and the pH of the gingival sulcus around the tooth were measured. The expression of acid-sensing ion channel 3 (ASIC3) in trigeminal ganglion neurons and phosphorylation of ASIC3 in the periodontal tissue were analyzed. The mechanical head-withdrawal reflex threshold to first molar stimulation and pH in the gingival sulcus decreased on day 1 after the elastic insertion. These decreases recovered to the sham level by buffering periodontal acidification. Periodontal inhibition of ASIC3 channel activity reversed the decreased mechanical head-withdrawal reflex threshold to first molar stimulation. On day 1 after elastic insertion, the tooth movement did not change the number of ASIC3 immunoreactive trigeminal ganglion neurons innervating the periodontal tissue but increased phosphorylated-ASIC3 levels in the periodontal tissue. Periodontal acidification induced by tooth movement causes phosphorylation of ASIC3, resulting in mechanical pain hypersensitivity in mechanically forced tooth.

Piezo1-pannexin-1-P2X3 axis in odontoblasts and neurons mediates sensory transduction in dentinal sensitivity.

According to the "hydrodynamic theory," dentinal pain or sensitivity is caused by dentinal fluid movement following the application of various stimuli to the dentin surface. Recent convergent evidence in Vitro has shown that plasma membrane deformation, mimicking dentinal fluid movement, activates mechanosensitive transient receptor potential (TRP)/Piezo channels in odontoblasts, with the Ca2+ signal eliciting the release of ATP from pannexin-1 (PANX-1). The released ATP activates the P2X3 receptor, which generates and propagates action potentials in the intradental Aδ afferent neurons. Thus, odontoblasts act as sensory receptor cells, and odontoblast-neuron signal communication established by the TRP/Piezo channel-PANX-1-P2X3 receptor complex may describe the mechanism of the sensory transduction sequence for dentinal sensitivity. To determine whether odontoblast-neuron communication and odontoblasts acting as sensory receptors are essential for generating dentinal pain, we evaluated nociceptive scores by analyzing behaviors evoked by dentinal sensitivity in conscious Wistar rats and Cre-mediated transgenic mouse models. In the dentin-exposed group, treatment with a bonding agent on the dentin surface, as well as systemic administration of A-317491 (P2X3 receptor antagonist), mefloquine and 10PANX (non-selective and selective PANX-1 antagonists), GsMTx-4 (selective Piezo1 channel antagonist), and HC-030031 (selective TRPA1 channel antagonist), but not HC-070 (selective TRPC5 channel antagonist), significantly reduced nociceptive scores following cold water (0.1 ml) stimulation of the exposed dentin surface of the incisors compared to the scores of rats without local or systemic treatment. When we applied cold water stimulation to the exposed dentin surface of the lower first molar, nociceptive scores in the rats with systemic administration of A-317491, 10PANX, and GsMTx-4 were significantly reduced compared to those in the rats without systemic treatment. Dentin-exposed mice, with somatic odontoblast-specific depletion, also showed significant reduction in the nociceptive scores compared to those of Cre-mediated transgenic mice, which did not show any type of cell deletion, including odontoblasts. In the odontoblast-eliminated mice, P2X3 receptor-positive A-neurons were morphologically intact. These results indicate that neurotransmission between odontoblasts and neurons mediated by the Piezo1/TRPA1-pannexin-1-P2X3 receptor axis is necessary for the development of dentinal pain. In addition, odontoblasts are necessary for sensory transduction to generate dentinal sensitivity as mechanosensory receptor cells.

Post-traumatic Trigeminal Neuropathy Associated With Endodontic Therapy: A Systematic Review.

A painful or non-painful trigeminal nerve lesion brought on by trauma that exhibits symptoms and/or clinical evidence of trigeminal nerve dysfunction is known as painful post-traumatic trigeminal neuropathy (PTTN). In relation to this, the term post-traumatic persistent dentoalveolar pain (PDAP) is an idiopathic condition of chronic neuropathic origin that manifests as a diagnostic challenge for dental practitioners. Neuropathic pain is defined by the International Association for the Study of Pain (IASP) as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." PDAP is located primarily in the teeth and jaws. This study systematically reviews how likely it is to get painful PTTN if the patient received endodontic therapy and the duration between doing root canal therapy (RCT) and getting PTTN. A systematic review was carried out using key search terms from PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) with English as the only permitted language. There were strict inclusion requirements. The 10 articles that were included showed a prevalence of an endodontic procedure anywhere from three to 48 months following post-endodontic treatment, and it mainly affects females in their mid-40s with no variation regarding the areas, whether it is in the maxilla or mandible. The lack of information about the association between RCT and PTTN led practitioners to make wrong diagnoses, which made the patient unwilling to seek further help. So, in this review, we identified some visible characteristics that can help in that process.