Genetic influence on treatment outcomes in patients with pain-related temporomandibular disorders.

BACKGROUND: Single nucleotide polymorphisms (SNPs) may influence pain susceptibility and impact treatment response in pain-related temporomandibular disorders (TMDp). OBJECTIVE: Explore the role of COMT (rs4646310, rs6269, rs4818, rs4680) and OPRM1 (rs1799971) genotypes in regulating treatment response. METHODS: Sixty TMDp patients (55 females and 5 males), diagnosed with the Diagnostic Criteria for TMD (DC/TMD), underwent standardised treatment (information and education, home physical therapy, occlusal splint) for 6 months. Treatment outcomes included: pain intensity, pain-free mouth opening, jaw functional limitation, depression, and anxiety. Genotyping for COMT and OPRM1 SNPs was performed using DNA from buccal mucosa swabs and TaqMan assays. Statistical analysis was carried out to compare the changes in treatment outcomes and the influence of genotypes on treatment response. RESULTS: Significantly less pain reduction was observed in minor allele carriers of rs4646310, and rs4680 compared to dominant homozygous (p < .025). Minor allele carriers of rs1799971 and rs4646310 demonstrated worsening in pain-free mouth opening while dominant homozygous exhibited improvement (p < .025). Significantly less anxiety reduction was observed in minor allele carriers of rs4646310 compared to dominant homozygous (p = .003). Of the all variables assessed in the regression model, carrying a minor allele of rs1799971 predicted a poorer treatment response considering pain-free mouth opening while carrying a minor allele of rs4646310 predicted less pain and less anxiety reduction. CONCLUSION: Our findings indicate that certain SNP variants of the COMT and OPRM1 genes were associated with poorer treatment response and may therefore play a significant role in the classification of TMDp patients. Also, assessment of patient genotype could potentially aid in predicting treatment response.

Association of Oxidative-Stress-Related Gene Polymorphisms with Pain-Related Temporomandibular Disorders and Oral Behavioural Habits.

The frequency of selected polymorphisms, one in each gene coding for proteins with antioxidative properties (CAT(rs1001179), SOD2(rs4880), GPX1(rs1050450), and NQO1(rs689452)), was compared between patients suffering from pain-related temporomandibular disorders (TMDp; n = 85) and control subjects (CTR; n = 85). The same was evaluated when participants were divided with respect to oral behavioural habits frequency into high-frequency parafunction (HFP; n = 98) and low-frequency parafunction (LFP; n = 72) groups. Another aim was to investigate whether polymorphisms in these genes can be associated with participants' psychological and psychosomatic characteristics. Polymorphisms were genotyped using the genomic DNA extracted from buccal mucosa swabs and real-time TaqMan genotyping assays. No differences in genotype distribution between TMDp patients and control subjects were found. Still, TMDp patients who were homozygous for minor allele A, related to the GPX1 polymorphism rs1050450, reported significantly more waking-state oral behaviours than GA + GG genotype carriers (score: 30 vs. 23, p = 0.019). The frequency of genotype AA for rs1050450 polymorphism was higher in HFP than in LFP participants (14.3% vs. 4.2%, p = 0.030). The most important predictors of waking-state oral behaviours were depression, anxiety, AA genotype (rs1050450), and female sex. The explored gene polymorphisms were not found to be significant risk factors for either TMDp or sleep-related oral behaviours. The association of waking-state oral behaviours with selected gene polymorphisms additionally supports previous assumptions that daytime bruxism is more closely linked to various stress manifestations, which might also be reflected through the variability related to the cellular antioxidative activity.

Association of oral behaviours and psychological factors with selected genotypes in pain-related TMD.

OBJECTIVES: To investigate frequency of single nucleotide polymorphisms (SNPs) in pain-related temporomandibular disorders (TMDp) and to determine whether specific SNPs, psychological, psychosomatic and behavioural characteristics are predictive for pain existence and intensity (low pain intensity (LPI)/high pain intensity (HPI)). METHODS: Genomic DNA was extracted from buccal mucosa swabs (85 TMDp;85 controls) for evaluating frequency of selected SNPs: catechol-O-methyltransferase (rs4680, rs4818), opiorphin (rs1387964), alpha subunit of voltage-gated sodium channel Nav1.1 (rs6432860) and voltage-gated sodium channel Nav1.9 (rs33985936). Participants completed questionnaires on somatosensory amplification, anxiety and depression symptoms and oral behaviours (OB). RESULTS: Sleep-related OB frequency was higher in TMDp patients compared to controls (p = 0.008). Compared to LPI, HPI patients had higher depression (p = 0.020) and anxiety scores (p = 0.017). TMDp group showed higher frequency of CC genotype (rs1387964) than controls (12.9% vs. 3.5%, p = 0.025). Following adjustments for age, sex and sleep-related OB, the significance of the recessive model (CC vs. TC + TT) between TMDp patients and controls was retained (OR = 5.783; 95%CI: 1.454-23.004). Frequency of GG genotype (rs4680 and rs4818) was higher in HPI compared to LPI patients (40% vs. 11.4%, p = 0.006; 24% vs. 3%; p = 0.012, respectively). The difference remained significant after adjusting for age, sex, depression, anxiety and sleep-related OB (rs4680: OR = 3.621; 95%CI: 1.580-8.297; rs4818: OR = 4.919, 95%CI: 1.641-14.746). CONCLUSION: This study has demonstrated that rs1387964 CC genotype was associated with TMDp while rs4680 GG and rs4818 GG genotypes contributed to HPI.

Association of oral behaviours' frequency with psychological profile, somatosensory amplification, presence of pain and self-reported pain intensity.

OBJECTIVE: To investigate the association of the frequency of oral behaviours with psychological (anxiety, depression) and psychosomatic factors (somatosensory amplification) as well as with pain presence (Temporomandibular disorders-pain (TMDp) patients and control (CTR) participants) and pain intensity (no_low pain intensity (nLPI)/high pain intensity (HPI)). MATERIAL AND METHODS: Fifty-four TMDp patients (48 females and 6 males; 29.13 ± 10.46 years) and 46 controls (29 females and 17 males; 28.54 ± 9.71 years) were administered Oral Behaviours Checklist (OBC), Generalized Anxiety Disorder-7 Scale, Patient Health Questionnaire-9 for depression and Somatosensory Amplification Scale. Data were analysed with respect to the presence of TMD pain and to pain intensity. Mann-Whitney test and Spearman's rank correlation were used for analyses. RESULTS: No significant differences in examined variables between TMDp patients and CTR individuals were found. The frequency of oral behaviors (OBC total score and sleep-related oral behaviours) as well as anxiety, depression and somatosensory amplification scores were higher in HPI group when compared to nLPI group (p < .05). In univariate correlations, oral behaviours were positively correlated with somatosensory amplification (p = .001), anxiety (p < .05), depression (p < .05), female sex (p < .05) and pain intensity (p < .05) but not with pain presence. Multiple linear regression models showed that predictors for the higher frequency of oral behaviours were anxiety and female sex. CONCLUSIONS: Oral behaviours were associated with pain intensity but not with pain presence and were primarily influenced by anxiety and female sex, suggesting that therapeutic approach should consider both, reducing pain intensity and management of the impact of psychological factors.Trial registration: ClinicalTrials.gov NCT04694274. Registered on 01/04/2021.

Sudden, Severe, Idiopathic Occlusal Relationship Change Coexisting with Pain-Related Temporomandibular Disorders: A Case Report.

The article presents a case of a young female patient who sought help due to myofascial pain followed by a sudden occlusal change (anterior open bite (AOB)) that occurred shortly after the administration of a soft night guard that had been previously provided by a general dentist. Palpation of the masseter and temporal muscles elicited the presence of familiar pain. After magnetic resonance imaging of temporomandibular joints, which ruled out disc displacement, the final diagnosis was myalgia. Since the patient had myalgia and malocclusion, the therapy included treatment of both conditions. Temporomandibular disorders (TMDs) management included a combination of kinesiotherapy, pharmacotherapy, and a stabilization splint. After TMD symptoms had resolved, the patient underwent an orthodontic evaluation. Cephalometric analysis revealed skeletal class II, retrognathic face, convex profile, and normal vertical growth pattern. Orthodontic treatment included a fixed appliance with vertical intermaxillary elastics. After 19 months of treatment, both sides achieved acceptable occlusion with Class I. Since the patient had myalgia and severe malocclusion, it was important to follow a systematic diagnostic and therapeutic workflow. Although it is impossible to establish a relationship between TMD symptoms and orthodontic therapy, patients who have TMD symptoms should have their pain resolved through a conservative treatment protocol before commencement of orthodontic treatment. The beginning of orthodontic therapy comes into consideration only when the TMD pain resolves.

Profiling of Patients with Temporomandibular Disorders: Experience of One Tertiary Care Center.

OBJECTIVES: The aim of this study was to assess typical and most prevalent characteristics of patients suffering from temporomandibular disorders (TMD) by a retrospective assessment of their medical records. MATERIAL AND METHODS: Demographic data and data on the characteristics of TMD were collected from the existing medical documentation of 304 TMD patients (250 females and 54 males) who had been referred to the Department of Dentistry, Clinical Hospital Center Zagreb from October 2016 to October 2020 due to temporomandibular pain. For the purpose of analysis, three age groups were formed: i) "children and adolescents" (up to 19 years of age); ii) "middle age" (from 20 to 50 years of age); iii) "older age" (>50 year- olds). A two-step cluster analysis was performed with the aim of classifying TMD patients into homogenous groups. RESULTS: The mean age of patients whose data were included in the study was 33.8 ± 16.66, with a significantly higher age in the group of women (p<0.001). Most of the patients had chronic pain (67.4%), with the ratio in favor of chronic patients being significantly higher in women than in men (p=0.001). Data on parafunctional behavior were confirmed in 14.5% of patients. Data on the onset of symptoms during/just after orthodontic treatment were present in 14.5% of patients. Data on spontaneous pain, assessed with a visual analogue scale, were recorded in 87 patients, with a mean of 6.14 ± 1.79 and with the highest pain in the "older age" group. Physical therapy was the most common therapeutic modality (56.3%) followed by an occlusal splint (40.5%). The analysis revealed 5 different clusters in the TMD patient data set. CONCLUSIONS: Our results are largely in line with current epidemiological knowledge on TMD. Women predominated in all age groups and most of the patients experienced chronic pain. Classifying patients into homogeneous groups using the clustering method could provide better identification of subgroups of conditions that mainly occur together in these patients, thus providing the basis for more specific management.

Treatment responses in chronic temporomandibular patients depending on the treatment modalities and frequency of parafunctional behaviour.

OBJECTIVES: (i) To evaluate the effect of three different interventions on treatment outcomes and (ii) to determine how the frequency of oral parafunction influences the effectiveness of the different therapeutic modalities. METHODS: Forty-five participants were randomly assigned into three treatment groups [physical therapy (PT), stabilisation splint (SS) and control therapy (CT)]. According to Oral Behavior Checklist score, participants were divided into "high-frequency parafunction" (HFP) and low-frequency parafunction" (LFP) group. Primary (spontaneous pain and characteristic pain intensity) and secondary outcomes (range of mouth opening, anxiety symptoms, quality of life, perceived stress and global functional limitation) were evaluated during six-month treatment period. RESULTS: Participants in PT group showed a significant reduction in characteristic pain intensity (p = .047, η2  = 0.243) when compared to SS and CT group, but significant improvement in spontaneous pain was found in all treatment groups. Patients treated with PT and SS exhibited significantly stronger improvement in pain-free mouth opening than patients in CT group (3rd month: p=.037, η2=0.258; 6th month: p = .005, η2  = 0.383). Within-group analyses showed significant decrease of perceived stress, anxiety symptoms and global functional limitation only in PT group over a six-month treatment period. Participants with HFP presented significantly greater levels of anxiety (3rd month: p = .009, η2  = 0.275; 6th month: p = .041, η2  = 0.176) than participants with LFP. Within-group analyses, however, showed significant improvement of anxiety, but also the decrease of perceived stress and improvement of global limitation for the HFP group but not for the LFP group. CONCLUSION: Although no treatment can be marked as superior in terms of spontaneous pain relief, PT was more effective when observing relief of characteristic pain intensity. In HFP group the reduction of anxiety, stress and functional limitation was present regardless of the applied therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04694274. Registered on 01/04/2021.