Mechanism of Catechol-O-methyltransferase Regulating Orofacial Pain Induced by Tooth Movement.

OBJECTIVE: To explore the mechanism of catechol-O-methyltransferase (COMT) in tooth movement pain. METHODS: The experimental groups were randomly allocated into the healthy control, sham operation, model, model+shCOMT experimental, model+shCOMT control, and model+COMT antagonist groups. A tooth movement pain model was established. The pain stimulation and behavior test were performed. The duration of grooming behavior was determined. The appropriate experimental force and duration for application were selected. COMT shRNA vector was constructed and packaged as adenovirus. The shCOMT adenovirus was injected into the left infraorbital foramen. Seven days later, the trigeminal ganglia of all treatment groups were obtained. The COMT and IL-17 expressions were detected by western blot. The appropriate COMT antagonist concentration was selected. The pathological results of each group were detected by HE staining. The tooth movement distance was determined. The COMT gene expression was detected by FISH. The COMT and IL-17 expressions in the right trigeminal ganglion tissue of each group were detected by western blot. RESULTS: The 60 g force and 14-day duration required the lowest stimulus intensity, the duration of grooming behavior was the longest, and the effect on COMT and IL-17 was the most significant. In the model group, formation of digestive cavity was seen in the trigeminal ganglion tissue, with infiltration of inflammatory cells, upregulation of the COMT and IL-17 expressions, and significant increase in the tooth movement distance. Compared with the model group, the shCOMT experimental group and the COMT antagonist group significantly improved the trigeminal ganglion tissue injury, significantly decreased the tooth movement distance, and significantly inhibited the COMT and IL-17 expressions. CONCLUSION: The efficiency of tooth movement can be influenced by interfering the COMT-related gene expression. This proves that the COMT system can regulate the orthodontic tooth movement pain.

Behavioral Responses and Expression of Nociceptin/Orphanin FQ and Its Receptor (N/OFQ-NOP System) during Experimental Tooth Movement in Rats.

Objective: To determine behavioral testing after experimental tooth movement in rats and to explore the role of nociceptin/orphanin FQ and its receptor (the N/OFQ-NOP system) in pain induced by experimental tooth movement. Design: The mouth-wiping behavior of rats was assessed by studying behavioral responses after experimental tooth movement. The distribution of N/OFQ in the periodontal ligament, the trigeminal ganglion (TG), and the caudal one-third of the trigeminal subnucleus caudalis (Vc) was assessed by immunohistochemistry. The variations in N/OFQ expression in the TG and Vc were measured by Western blotting. The ongoing changes in the gene expression of the prepronociceptin gene and opioid receptor-like 1 receptor were assessed in the TG and Vc by real-time polymerase chain reaction (RT-PCR). Results: Overall, the mouth-wiping behavior increased significantly. The behavior first increased and then gradually decreased to a low level, showing cyclical variation. N/OFQ immunoreactivity increased in the periodontal ligament after tooth movement. ppN/OFQ mRNA and protein levels showed a time-dependent increase in the TG and were positively correlated with pain stimulus. NOP gene levels showed large fluctuations. In the Vc, the expression and changes in the N/OFQ-NOP system showed the opposite trend as those noted in TG and the periodontal membrane. Conclusion: The N/OFQ system may have a complex regulatory function in the pain induced by tooth movement and may be related to inflammation caused by orthodontic tooth movement and periodontal damage. The specific mechanism remains to be further studied.

Lidocaine coinfusion alleviates vascular pain induced by hypertonic saline infusion: a randomized, placebo-controlled trial.

BACKGROUND: Hypertonic saline solution has been frequently utilized in clinical practice. However, due to the nonphysiological osmolality, hypertonic saline infusion usually induces local vascular pain. We conducted this study to evaluate the effect of lidocaine coinfusion for alleviating vascular pain induced by hypertonic saline. METHODS: One hundred and six patients undergoing hypertonic saline volume preloading prior to spinal anesthesia were randomly allocated to two groups of 53 each. Group L received a 1 mg/kg lidocaine bolus followed by infusion of 2 mg/kg/h through the same IV line during hypertonic saline infusion; Group C received a bolus and infusion of normal saline of equivalent volume. Visual analogue scale (VAS) scores of vascular pain were recorded every 4 min. RESULTS: The vascular pain severity in Group L was significantly lower than that in Group C for each time slot (P < 0.05). The overall incidence of vascular pain during hypertonic saline infusion in Group L was 48.0%, which was significantly lower than the incidence (79.6%) in Group C (P < 0.05). CONCLUSION: Lidocaine coinfusion could effectively alleviate vascular pain induced by hypertonic saline infusion. TRIAL REGISTRATION: Chinese Clinical Trial Registry, number: ChiCTR1900023753 . Registered on 10 June 2019.

Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-mediated inflammation.

OBJECTIVE AND DESIGN: Microglia stimulated by oxygen glucose deprivation (OGD) were treated with quercetin to investigate the effect on oxidative stress and the inflammatory response and to explore whether toll-like receptor 4 (TLR4) signaling was involved. In addition, the effect of quercetin on the neurological functions of neonatal mice with hypoxic-ischemic brain injury (HIBI) was examined. MATERIALS AND SUBJECTS: Mouse BV2 microglial cells and postnatal day 7 neonatal mice were used. TREATMENT: A predetermined concentration of quercetin was used in cell experiments. Quercetin was injected i.p. (50 mg/kg) at three time points after HI insult: 0, 24, and 48 h. METHODS: Cell viability assay, Western blotting, qRT-RCR, ELISA, HIBI model construction and behavioral tests. RESULTS: This study first showed that quercetin protected BV2 cells from OGD-induced damage and reversed the changes in microglial oxidative stress-related molecules. Second, quercetin inhibited OGD-induced expression of inflammatory factors in BV2 cells and suppressed TLR4/MyD88/NF-κB signaling. Finally, quercetin was disclosed to be effective in mitigating cerebral infarct volume and cognitive and motor function deficits in HIBI mice. CONCLUSION: These results suggest that the neuroprotective effect of quercetin in HIBI mice is partially due to the inhibition of oxidative stress and TLR4-mediated inflammatory responses in activated microglia.

MicroRNA expression profile of human periodontal ligament cells under the influence of Porphyromonas gingivalis LPS.

Periodontitis is a chronic inflammatory disease which is caused by bacterial infection and leads to the destruction of periodontal tissues and resorption of alveolar bone. Thus, special attention should be paid to the mechanism under lipopolysaccharide (LPS)-induced periodontitis because LPS is the major cause of periodontitis. However, to date, miRNA expression in the LPS-induced periodontitis has not been well characterized. In this study, we investigated miRNA expression patterns in LPS-treated periodontal ligament cells (PDLCs). Through miRNA array and differential analysis, 22 up-regulated miRNAs and 28 down-regulated miRNAs in LPS-treated PDLCs were identified. Seven randomly selected up-regulated (miR-21-5p, 498, 548a-5p) and down-regulated (miR-495-3p, 539-5p, 34c-3p and 7a-2-3p) miRNAs were examined by qRT-PCR, and the results proved the accuracy of the miRNA array. Moreover, targets of these deregulated miRNAs were analysed using the miRWalk database. Database for Annotation, Visualization and Integration Discovery software were performed to analyse the Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway of differential expression miRNAs, and the results shown that Toll-like receptor signalling pathway, cAMP signalling pathway, transforming growth factor-beta signalling pathway, mitogen-activated protein kinase (MAPK) signalling pathway and other pathways were involved in the molecular mechanisms underlying LPS-induced periodontitis. In conclusion, this study provides clues for enhancing our understanding of the mechanisms and roles of miRNAs as key regulators of LPS-induced periodontitis.

Validity assessment and determination of the cutoff value for the Index of Complexity, Outcome and Need among 12-13 year-olds in Southern Chinese.

To validate the use of the Index of Complexity, Outcome and Need (ICON) in assessing orthodontic treatment need among 12-13 year-olds in southern China, we determined the threshold value of ICON based on Chinese orthodontists' judgments. The samples consisted of 335 students in grade 7 from 16 randomly selected middle schools in Chengdu, China. Three associate professors provided ICON scores for each participant and the results were compared with the gold standard judgments from 25 experts on treatment needs. Based on the gold standard, 195 casts belonged to the treatment category, while the rest 140 belonged to the no-treatment category. With the international cutoff point of 43, the sensitivity and specificity of the ICON score were 0.29 and 0.98.The best compromise between sensitivity and specificity in Chengdu, compared with the gold standard, was found at a cutoff point of 29, and the sensitivity and specificity were 0.88 and 0.83. When used to evaluate the treatment need of 12-13 year-olds in southern China, the international ICON cutoff value did not correspond well with Chinese orthodontists' judgments; a lower cutoff value of 29 offered a greater sensitivity and specificity with respect to expert orthodontists' perception of treatment need.

Efficacy of botulinum toxins on bruxism: an evidence-based review.

The objective of this study was to assess the efficacy of botulinum toxins on bruxism. Electronic databases (PubMed, Embase and Science Citation Index), websites (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) and the literature database of SIGLE (System for Information on Grey Literature in Europe) were searched from January 1990 to April 2011 for randomised controlled trials or nonrandomised studies assessing the efficacy of botulinum toxins on bruxism. There was no language restriction. Through a predefined search strategy, we retrieved 28 studies from PubMed, 94 from Embase, 60 from the Science Citation Index, two ongoing clinical trials and two from the Cochrane Central Register of Controlled Trials. Of these, only four studies met our inclusion criteria and were finally included. Of the four included studies, two were randomised controlled trials and two were controlled before-and-after studies. These studies showed that botulinum toxin injections can reduce the frequency of bruxism events, decrease bruxism-induced pain levels and satisfy patients' self-assessment with regard to the effectiveness of botulinum toxins on bruxism. In comparison with oral splint, botulinum toxins are equally effective on bruxism. Furthermore, botulinum toxin injections at a dosage of <100 U are safe for otherwise healthy patients. Botulinum toxin injections are effective on bruxism and are safe to use. Therefore, they can be used clinically for otherwise healthy patients with bruxism.

3D-fEA of stress levels and distributions for different bases under a Class I composite restoration.

PURPOSE: To investigate the level and distribution of stresses in composite-restored mandibular first molars with various combinations of base materials. METHODS: The finite element package Abaqus was used for the stress analysis. Several different base materials were evaluated [light-cured glass ionomer (LC-GI), chemically-cured calcium hydroxide (CC-CH), and light-cured calcium hydroxide (LC-CH)] in combination with light-cured composite (LC-CP). Four models of restored molars with Class I deep cavity preparations were simulated, including (1) LC-GI/LC-CP, (2) CC-CH/LC-CP, (3) CC-CH/LC-GI/LC-CP, and (4) LC-CH/LC-GI/LC-CP. A 250N static single-point load was applied vertically on the central fossa of the tooth to simulate physical loading conditions. RESULTS: In each case, the peak stresses were found to be concentrated mainly at the interfaces between the various materials and the dental tissues. In the residual tooth structures, the maximum Von Mises stresses were 20.01 MPa in model LC-GI/LC-CP, 23.85 MPa in model CC-CH/LC-CP, 23 MPa in model CC-CH/LC-GILC-CP and 21.83 MPa in model LC-CH/LC-GIILC-CP. In the LC-CP restorations, the maximum Von Mises stresses were 43.68 MPa in model LC-GILC-CP, 42.24 MPa in model CC-CH/LC-CP, 42.29 MPa in model CC-CH/LC-G/LC-CP and 42.55 MPa in model LC-CH/LC-GI/LC-CP. In the bases, the maximum Von Mises stresses were 5.71 MPa in model LC-GI/LC-CP, 0.85 MPa in model CC-CH/LC-CP, 4.69 MPa in model CC-CH/LC-GI/LC-CP, and 4.93 MPa in model LC-CH/LC-GILC-CP.

Initial arch wires for alignment of crooked teeth with fixed orthodontic braces.

BACKGROUND: The initial arch wire is the first arch wire to be inserted into the fixed appliance at the beginning of orthodontic treatment and is used mainly for correcting crowding and rotations of teeth. With a number of orthodontic arch wires available for initial tooth alignment, it is important to understand which wire is most efficient, as well as which wires cause the least amount of root resorption and pain during the initial aligning stage of treatment. OBJECTIVES: To identify and assess the evidence for the effects of initial arch wires for alignment of teeth with fixed orthodontic braces in relation to alignment speed, root resorption and pain intensity. SEARCH STRATEGY: We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (30th November 2009), CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to 30th November 2009) and EMBASE (1980 to 30th November 2009). Reference lists of articles were also searched. There was no restriction with regard to publication status or language of publication. We contacted all authors of included studies to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of initial arch wires to align crooked teeth with fixed orthodontic braces were selected. Only studies involving patients with upper and/or lower full arch fixed orthodontic appliances were included. DATA COLLECTION AND ANALYSIS: Two review authors were responsible for study selection, validity assessment and data extraction. All disagreements were resolved by discussion amongst the review team. Corresponding authors of included studies were contacted to obtain missing information. MAIN RESULTS: Seven RCTs, with 517 participants, provided data for this review. Among them, five trials investigated the speed of initial tooth alignment comparing: 0.016 inch ion-implanted A-NiTi wire versus 0.016 inch A-NiTi versus 0.0175 multistrand stainless steel wire; 0.016x0.022 inch medium force active M-NiTi wire versus 0.016x0.022 inch graded force active M-NiTi wire versus 0.0155 inch multistrand stainless steel wire; 0.016 inch superelastic NiTi wire versus 0.016 inch NiTi wire; 0.014 inch superelastic NiTi wire versus 0.0155 inch multistrand stainless steel wire; 0.016 inch CuNiTi wire versus 0.016 inch NiTi wire. The other two studies investigated pain intensity experienced by patients during the initial stage of treatment comparing: 0.014 inch superelastic NiTi wire versus 0.014 inch NiTi wire; 0.014 inch superelastic NiTi wire versus 0.015 inch multistrand stainless steel wire. Data analyses were often inappropriate within the included studies. AUTHORS' CONCLUSIONS: There is some evidence to suggest that there is no difference between the speed of tooth alignment or pain experienced by patients when using one initial aligning arch wire over another. However, in view of the general poor quality of the including trials, these results should be viewed with caution. Further RCTs are required.

Trigeminal expression of N-methyl-D-aspartate receptor subunit 1 and behavior responses to experimental tooth movement in rats.

OBJECTIVE: To test the hypothesis that peripheral N-methyl-D-aspartate (NMDA) receptors play a role in pain induced by experimental tooth movement. MATERIALS AND METHODS: Male Sprague-Dawley rats weighing between 200 g and 300 g were used in this study. Expression of NMDA receptors subunit 1 (NMDAR1) in the mandibular portion of the trigeminal ganglion (TG) was determined by Western blotting 4 hours and 1, 2, 3, 5, 7, and 14 days after tooth movement. Changes in the time taken by the rats on nocifensive behavior then effects of NMDA receptor antagonist MK-801 and force magnitude on these changes in behavior and NMDAR1 expression were evaluated. RESULTS: Experimental tooth movement led to a statistically significant increase in NMDAR1 expression at protein level from day 1 to 7 after force application initiating tooth movement. Time spent on nocifensive behavior dramatically increased from day 1 to 7. The rhythm in NMDAR1 expression in the TG and behavioral activities correlated well with the initial orthodontic pain responses. The magnitude of the nocifensive behavior and NMDAR1 expression were both force magnitude dependent and could be reduced by peripheral NMDA receptor antagonist MK-801. CONCLUSIONS: The hypothesis is accepted. Peripheral NMDA receptors are modulated by experimental tooth movement and involved in the development of tooth movement pain.

[Analysis of clinical features and mutation associated with oligodontia].

OBJECTIVE: To investigate the mutation characteristics of paired box homeotic gene 9 (PAX9) and muscle segment homeobox gene 1 (MSX1) of patients with congenital oligodontia. METHODS: Clinical manifestations were recorded by taking complete oral examinations in patients with congenital nonsyndromic oligodontia and some of his normal family members. Pedigree information was confirmed by extended interviews and a pedigree was constructed. Inheritance mode and clinical features were analyzed. Assessment of crown width compared to normal value of crown width in Chinese people was based on the registrations and measurements of study cast. Comparison of craniofacial form, malocclusion types and characteristics were conducted via cephalometric analysis by taking lateral cephalometric radiographics. Venous blood samples were collected and DNA was extracted from leukocytes. DNA sequencing and mutation analysis were analyzed in exon 1, 2, 3, 4 of PAX9 and exon 1, 2 of MSX1 coding region by polymerase chain reaction (PCR). RESULTS: The teeth shape abnormality of the patient was noticed by a measured smaller crown width compared to normal values of crown width in Chinese people. The result of cephalometric analysis indicated no obvious inherited tendency in the proband in terms of facial osseo type and jaw bone pattern. One mutation was found in the proband and his mother in exon 3 of PAX9, the missense mutation G718C causing a conservative change A240P was present. Mutation was not found in MSX1. CONCLUSION: These findings suggest that the missense mutation G718C in exon 3 of PAX9 is likely the cause of oligodontia.

Behavioural responses and expression of P2X3 receptor in trigeminal ganglion after experimental tooth movement in rats.

OBJECTIVE: To explore the role of P2X(3) receptor in pain induced by experimental tooth movement. DESIGN: Male Sprague-Dawley rats weighing 200-300g were used. P2X(3) receptor distribution in the caudal one-third portion of the trigeminal ganglion (TG) was studied by IHC. Next, the changes of P2X(3) expression were detected by Western blotting 4h, 1d, 2d, 3d, 5d, 7d, 14d after tooth movement. We then developed a behaviour pain model associated with directed mouth wiping. Finally, the effect of TNP-ATP on nociceptive-like behaviour was evaluated. RESULTS: Our results showed that P2X(3) receptors were expressed mainly in small- and medium-sized cells and experimental tooth movement led to an increase in staining of mandibular P2X(3) receptors. In addition, following experimental tooth movement, the expression of P2X(3) receptor in TG was statistically significantly up-regulated from days 1 to 5, with a peak on day 3. It was also found that the time spent on directed mouth wiping was dramatically increased by experimental tooth movement from days 1 to 7. The rhythm change of P2X(3) receptor expression in TG and the mouth wiping behaviour were in concert with the initial orthodontic pain responses. The directed mouth wiping behaviour was modulated in a force-dependent manner and could be attenuated by peripheral and systemic morphine. Furthermore, peripherally administered TNP-ATP could exert an analgesic effect on this pain model. CONCLUSION: These results suggest that directed mouth wiping behaviour can be a reliable measurement of pain following experimental tooth movement in rats. The P2X(3) receptor is important in the development and maintenance of tooth movement pain and thus may be peripheral targets for analgesics in orthodontic pain control.

[Facial profile preference among four panels].

OBJECTIVE: To determine the facial profile preference among four groups of persons and the influence of vertical proportion and skeletal anteroposterior relation on facial profile esthetics. METHODS: One hundred and twenty persons, comprising of adult patients, adolescents' parents, laypersons and orthodontists, participated this study. The subjects were asked to rate 27 silhouettes which represented the male facial profiles with various vertical proportion and anteroposterior relation. RESULTS: The silhouette II-1s scored highest while the one III-4s scored lowest (P < 0.05). The silhouette I-normal was rated highest by orthodontists while the ones II-normal and II-1s were rated highest by other three groups. The silhouette III-4s was scored lowest by all groups (P < 0.05). CONCLUSIONS: Vertical discrepancy had influence on Chinese male facial profile esthetics and the influence was related to the degree of vertical malformation and skeletal anteroposterior relation. Class III skeletal pattern had the most negative influence on male profile esthetics. The four panels had different esthetic standard. The preference of facial profile esthetics was related to orthodontic education background rather than gender or age.