Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.

Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a genome-wide association study assuming an additive genetic model of TMD in a discovery cohort of 999 cases and 2031 TMD-free controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Using logistic models adjusted for sex, age, enrollment site, and race, we identified 3 distinct loci that were significant in combined or sex-segregated analyses. A single-nucleotide polymorphism on chromosome 3 (rs13078961) was significantly associated with TMD in males only (odds ratio = 2.9, 95% confidence interval: 2.02-4.27, P = 2.2 × 10). This association was nominally replicated in a meta-analysis of 7 independent orofacial pain cohorts including 160,194 participants (odds ratio = 1.16, 95% confidence interval: 1.0-1.35, P = 2.3 × 10). Functional analysis in human dorsal root ganglia and blood indicated this variant is an expression quantitative trait locus, with the minor allele associated with decreased expression of the nearby muscle RAS oncogene homolog (MRAS) gene (beta = -0.51, P = 2.43 × 10). Male mice, but not female mice, with a null mutation of Mras displayed persistent mechanical allodynia in a model of inflammatory pain. Genetic and behavioral evidence support a novel mechanism by which genetically determined MRAS expression moderates the resiliency to chronic pain. This effect is male-specific and may contribute to the lower rates of painful TMD in men.

Therapeutic effectiveness of a combined counseling plus stabilization appliance treatment for myofascial pain of the jaw muscles: A pilot study.

OBJECTIVE: This study aims to assess changes over time in pain intensity (VAS) and in pressure pain threshold (PPT) of the anterior temporalis and masseter muscles with a treatment protocol combining counseling and stabilization appliance as well as its effects on psychosocial factors. METHODS: Twenty individuals with myofascial pain of jaw muscles lasting from at least six months were selected for an uncontrolled before-after study. Counseling was performed by giving information on myofascial pain and advice on self-management. Stabilization appliances were delivered one week after the first counseling session. A number of outcome variables (i.e. visual analogue scale [VAS], pain pressure threshold [PPT] and Research Diagnostic Criteria for Temporomandibular Disorders axis II [RDC/TMD]) were assessed at different evaluation points during a six-month follow-up. ANOVA for repeated measures and Pearson's correlation test were used to evaluate changes in the outcome variables over time. RESULTS: Compared to baseline data, a significant positive change was found at the 1st week, 1st, 3rd, and 6th month evaluations for VAS values (P < 0.0001) and at the 1st week, 3rd, and 6th month evaluations for PPT values (P < 0.05). RDC/TMD axis II values were significantly different (P < 0.05) from baseline to all evaluations points. CONCLUSION: The association of counseling and stabilization appliance is effective in the management of chronic myofascial pain of jaw muscles. Future controlled studies are required to get deeper into the assessment of the relative effectiveness of counseling and stabilization appliances.

The relationship between occlusal support and maxillary development: An animal study.

OBJECTIVE: To test the hypothesis that maxillary development may be affected by occlusal support. MATERIALS AND METHODS: The sample was composed by Wistar rats (5 weeks old) divided into three groups: Control (n = 10), extraction of mandibular molar teeth - left side (n = 10), extraction mandibular molar teeth - left and right sides (n = 10). The rats were sacrificed 8 weeks postextraction. Cone beam computed tomography scan images were taken for posterior measurement of maxillary length and width. Data were analyzed by one-way analysis of variance (Tukey test as post-hoc test). RESULTS: Maxillary length was significantly shorter (P < 0.005) in both groups after tooth extraction. No difference was observed regarding maxillary width and body weight. CONCLUSION: Reduced occlusal support may impair the development of the maxilla in rats.

COMT gene locus: new functional variants.

Catechol-O-methyltransferase (COMT) metabolizes catecholaminergic neurotransmitters. Numerous studies have linked COMT to pivotal brain functions such as mood, cognition, response to stress, and pain. Both nociception and risk of clinical pain have been associated with COMT genetic variants, and this association was shown to be mediated through adrenergic pathways. Here, we show that association studies between COMT polymorphic markers and pain phenotypes in 2 independent cohorts identified a functional marker, rs165774, situated in the 3' untranslated region of a newfound splice variant, (a)-COMT. Sequence comparisons showed that the (a)-COMT transcript is highly conserved in primates, and deep sequencing data demonstrated that (a)-COMT is expressed across several human tissues, including the brain. In silico analyses showed that the (a)-COMT enzyme features a distinct C-terminus structure, capable of stabilizing substrates in its active site. In vitro experiments demonstrated not only that (a)-COMT is catalytically active but also that it displays unique substrate specificity, exhibiting enzymatic activity with dopamine but not epinephrine. They also established that the pain-protective A allele of rs165774 coincides with lower COMT activity, suggesting contribution to decreased pain sensitivity through increased dopaminergic rather than decreased adrenergic tone, characteristic of reference isoforms. Our results provide evidence for an essential role of the (a)-COMT isoform in nociceptive signaling and suggest that genetic variations in (a)-COMT isoforms may contribute to individual variability in pain phenotypes.

Effect of surface treatments on the bond strength of different resin teeth to complete denture base material.

Although different commercial brands of artificial teeth are available in the market, debonding from the denture base is still an issue when rehabilitating edentulous patients with conventional or implant-supported complete dentures. The purpose of this study was to investigate the effect of surface treatments on the bond strength of four artificial teeth brands to a denture base material polymerized by microwave energy. Forty anterior artificial teeth of each brand (Biolux, Trilux, Biotone IPN, and Vipi Dent Plus) were bonded to denture base material (VipiWave). Before processing, groups often specimens of each brand received surface treatment: control, monomer application (MA), air abrasion (AA) or diatoric cavity (DC). After processing, a blinded examiner conducted the bond test by applying load to the specimens (0.5 mm/min, to 45 degrees). Data were analyzed by one-way ANOVA followed by Tukey's test (alpha = 0.05). Biolux teeth have stronger bonding to denture base than Trilux (p < 0.05) in control group; higher bond values than Biotone IPN (p < 0.05) in MA group; and higher bond strength than Vipi Dent Plus and Trilux (p < 0.01) in DC group; AA had no differential effect for any of the brands. With regard to the effect of the surface treatments on bond strength within groups of commercial brand, statistical analysis revealed no difference among them. According to results in general, Biolux teeth had the strongest bonding to the denture base material polymerized by microwave energy. Results may assist dentists in selecting denture teeth from the standpoint of shear bond strength.

Effect of surface treatments on the bond strength of different resin teeth to complete denture base material. / Effect of surface treatments on the bond strength of different resin teeth to complete denture base material.

Although different commercial brands of artificial teeth are available in the market, debonding from the denture base is still an issue when rehabilitating edentulous patients with conventional or implant-supported complete dentures. The purpose of this study was to investigate the effect of surface treatments on the bond strength of four artificial teeth brands to a denture base material polymerized by microwave energy. Forty anterior artificial teeth of each brand (Biolux, Trilux, Biotone IPN, and Vipi Dent Plus) were bonded to denture base material (VipiWave). Before processing, groups often specimens of each brand received surface treatment: control, monomer application (MA), air abrasion (AA) or diatoric cavity (DC). After processing, a blinded examiner conducted the bond test by applying load to the specimens (0.5 mm/min, to 45 degrees). Data were analyzed by one-way ANOVA followed by Tukeys test (alpha = 0.05). Biolux teeth have stronger bonding to denture base than Trilux (p < 0.05) in control group; higher bond values than Biotone IPN (p < 0.05) in MA group; and higher bond strength than Vipi Dent Plus and Trilux (p < 0.01) in DC group; AA had no differential effect for any of the brands. With regard to the effect of the surface treatments on bond strength within groups of commercial brand, statistical analysis revealed no difference among them. According to results in general, Biolux teeth had the strongest bonding to the denture base material polymerized by microwave energy. Results may assist dentists in selecting denture teeth from the standpoint of shear bond strength.

Influence of re-using reversible hydrocolloids on the linear alteration of coating models.

Reusing reversible hydrocolloids too many times may cause alterations of the coating model and produce unsatisfactory RPPs. The aim of this study was to analyze the linear alterations of coating models reproduced from molds obtained with two commercial brands of reversible hydrocolloid (RH) with 15 reuse cycles of the material. A metal model was used with 4 marks (A, B, C and D) on which the distances AB, BC, CD, DA, BD and AC could be measured lineally. Ten models were divided into two groups according commercial brand of RH: group VIPI-Duplicator VIPI and group K27--Duplicator K27l. The RH was heated in a microwave oven and poured into a flask containing the model. The mold was filled with the ethyl silicate coating, and after crystallization, refractory models were obtained. This was repeated in the 15 re-use cycles of each RH. The refractory models obtained from the 1st, 5th, 10th and 15th times of re-use of RHs were measured under a measuring microscope. The means were submitted to the Analysis of Variance, Tukey and Dunnet tests, to a 5% level of significance. Group VIPI showed linear alterations in relation to the plaster models, for distances AB (1 use = -1.25% and 5th re-use = -1.20%); AD (1st use = 0.76%, 10th re-use = 0.65% and 15th re-use = 0.52%); BD (1st use = 0.58%). Both commercial brands analyzed produced coating models with acceptable linear alterations in up to 15 reuse cycles, no statistical difference being observed between them.

Effect of double flasking and investing methods on artificial teeth movement in complete dentures processing.

PURPOSE: The aim of this study was to evaluate linear dimensional alterations of artificial teeth for complete dentures when using different investment and flasking techniques. BACKGROUND: Dimensional changes in the vertical dimension may occur owing to changes in artificial teeth positioning caused by different investing and flasking techniques. MATERIALS AND METHODS: Thirty pairs of the complete dentures were manufactured and randomly divided into three groups (n = 10): (1) invested with type III stone in monomaxillary PVC flask; (2) invested with type III stone in bimaxillary PVC flask; and (3) invested with laboratory silicone in bimaxillary PVC flask. Dentures were polymerised by microwave, and 12 linear distances were measured before and after denture processing. Data were analysed by one-way anova, considering manufacturing technique as the study factor. Tukey's HSD was used as post hoc ANOVA (p = 0.05). RESULTS: Most of the linear distances were comparable for all groups. All transversal maxillary and mandibular distances were higher for group 1 compared with groups 2 and 3 (p < 0.05), except the distance 3-6 for mandibular arch, in which no difference was found between groups (p < 0.05). Both maxillary diagonal distances were higher in group 1 (p < 0.05), and no differences were found among all groups for mandibular measurements. CONCLUSIONS: Double flasking technique independent on the investment material is shown to be the most effective method to reduce changes in artificial teeth positioning.

Influence of different flasking and polymerizing methods on the occlusal vertical dimension of complete dentures.

The flasking and polymerization technique for resins can introduce stresses during processing which may lead to denture base distortions, artificial teeth displacement and increases in the occlusal vertical dimension (OVD). This study investigated whether the association of microwave heat-activation (MH) and bimaxillary flasking (BF) minimizes the possible increases in OVD after prostheses processing. Forty pairs of complete dentures were waxed with the artificial teeth in closed occlusion and divided into four groups according to investing and heating methods: G1 (control) = monomaxillary/water bath; G2 = monomaxillary/microwave; G3 = bimaxillary/water bath and G4 = bimaxillary/microwave. OVD was measured using a digital caliper before and after prostheses processing. Results were submitted to statistical analysis (Student's t-test for multiple comparisons and post hoc ANOVA, alpha = 0.05). Comparison of values before and after processing showed that OVD increased in all groups after polymerization (p < 0.001), regardless of flasking and polymerization methods. Statistically, G2 had the greatest difference in OVD when compared to G1 (p = 0.014), G3 (p = 0.019) and G4 (p = 0.024). G3 and G4 showed similar results statistically when compared to G1 (control). Both investing and heating methods resulted in an increase in OVD after processing. However, the prostheses invested in bimaxillary flasks showed the lowest changes in OVD, regardless of the polymerization method.

The influence of double flask investing on tooth displacement in dentures processed by microwave irradiation.

OBJECTIVE: This study evaluated the influence of the bimaxillary flask (BMF) and two different investing materials on first molar inclination in dentures processed by microwave irradiation. BACKGROUND: The BMF may minimise tooth displacement, saving time and improving occlusion. METHODS AND MATERIALS: Forty pairs of dentures were randomised into four groups: stone wall in monomaxillary flask; silicone wall in BMF; stone wall in BMF; acrylic resin retentions and silicone in BMF. Dentures were processed by microwave irradiation. Two referential points were established on tooth surface. A microscope and a digital pachymeter were used to measure the distance between these points, and the angles α (right maxillary molar), ß (left maxillary molar), α' (right mandibular molar) and ß' (left mandibular molar) were calculated by the law of cosines. Data were submitted to Kruskal-Wallis (5% significance). RESULTS: No difference was observed among the groups (p > 0.05). In the intra-group analysis, α was significantly different for groups I, II and III; α', for groups II and IV; ß, for all groups; ß', for groups III and IV. CONCLUSION: First molar inclination was similar for monomaxillary and BMFs. The use of stone or silicone as investing materials presented the same effect on tooth inclination.

Genomics and the new perspectives for temporomandibular disorders.

The field of temporomandibular disorders (TMD) is experiencing significant changes in terms of aetiology and treatment. Researchers and clinicians are becoming increasingly aware of the possibility that genetic variations may play a role in pain perception and onset of TMD. In this review, we purpose to briefly describe these allelic variants, how they may be involved in TMD pathophysiology and how they may affect TMD treatment. Studies have already pointed the association between TMD and genetic polymorphisms in the oestrogen receptor alpha, adrenergic receptor beta 2, serotonin receptor, serotonin transporter and catechol-O-methyltransferase genes, and other candidate genes continue to emerge. The main implication of these findings refers to the promising possibilities of "genome/omics-based personalised care", which consists of tailoring individual treatment based on personalised medication, depending on the individual genetic differences and early diagnosis and prognosis of the disorder, preventing acute pain conditions from becoming chronic. The following years of research shall focus on collecting and endorsing these findings if we are to provide patients in pain with efficient and successful TMD treatments.

Water sorption of heat-polymerized acrylic resins processed in mono and bimaxillary flasks.

This study evaluated water sorption in heat-polymerized acrylic resins processed in monomaxillary flasks by water bath and in bimaxillary flasks by microwave energy and water bath. Fifty heat-polymerized acrylic resin specimens were fabricated according to the 12th specification of the American Dental Association and assigned to 3 groups: group 1 was processed by water bath in monomaxillary metallic flask; group 2 was processed by microwave energy in bimaxillary PVC flask; and group 3 was processed by water bath in bimaxillary metallic flask. Specimens were submitted to water sorption test, means were calculated and analyzed statistically by Student's t-test. Means (in g/cm3) were: group 1--0.024085, group 2--0.025312 and group 3--0.022098. Microwave energy processing and the amount of stone and resin used in the bimaxillary PVC flask did not influence water sorption; specimens processed in bimaxillary metallic flask by water bath presented lower water sorption means, suggesting an inadequate polymerization of the acrylic resin mass.

Surface roughness of acrylic resins processed by microwave energy and polished by mechanical and chemical process

The aim of this study was to evaluate the influence of polymerization methods (microwave energy - MW, and water bath - WB) and polishing techniques (chemical - C and mechanical - M) on the surface roughness of one heat-polymerized acylic resin (Vipi-Cril). Forty acrylic resin disk-shaped samples were made according to ADA specification nº 12. Half of samples were processed by microwave energy (500W for 3 minutes), and the other half by water bath (74±1 ºC for 9 hours). After deflasking, the samples were trimmed with a sequence of abrasive aluminum oxide sandpapers of different grades (180, 220 and 400) and divided in 4 groups according to polymerization methods and polishing techniques: G1: MW+CP, G2: MW+MP, G3: WB+CP and G4: WB+MP. Surface roughness values were measured using a Surfcorder SE 1700 rugosimeter (Kosaka Laboratory Ltd, Kosaka, Japan). Mann-Whitney test (p=.05) indicated significant differences between polishing methods processed by microwave energy (p= .0018), and between polishing methods processing by water bath (p= .0002). Samples processed by both methods (water bath or microwave energy) showed smoother surfaces when polished by mechanical polishing method, and polymerization methods did not influence in surface roughness.

Water sorption of heat-polymerized acrylic resins processed in mono and bimaxillary flasks

A finalidade deste estudo foi avaliar a sorção de água de resinas acrílicas ativadas termicamente quando processada em mufla monomaxilar para banho de água e mufla bimaxilar para banho de água e microondas. Foram confeccionados 50 corpos-de-prova de resina acrílica ativada termicamente de acordo com a especificação nº 12 da American Dental Asociation, divididos em três grupos: no grupo 1, os corpos-de-prova foram processados em mufla monomaxilar metálica para banho de água; no 2 foram processados em mufla bimaxilar de PVC para uso em microondas e no 3 foram processados em mufla bimaxilar metálica para banho de água. Os corpos-de-prova foram submetidos ao ensaio de sorção de água, os valores médios foram calculados e analisados pelo teste t de Student. Os valores obtidos (g/cm3) foram: grupo 1 - 0,024085, grupo 2 - 0,025312 e grupo 3 - 0,022098. A polimerização da resina acrílica por energia de microondas na mufla bimaxilar de PVC não influenciou a sorção de água em relação ao processamento em muflas monomaxilares, enquanto a polimerização feita em muflas bimaxilares metálicas aquecidas em banho de água diminuiu esse índice, sugerindo inadequada polimerização da massa de resina.