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BACKGROUND: Oral food processing is an important part of daily food intake. A major part of this process is mastication, which prepares a bolus of food for swallowing by mechanically crushing and grinding ingested food between the teeth using rhythmic movements. Masticatory dysfunction is common in the elderly and in some neurological disorders and can have serious negative health consequences. OBJECTIVE: This study investigated the effect of restricted mastication, achieved by experimentally reducing the duration of mastication, on masticatory patterns and subsequent swallowing function. METHODS: Thirty healthy men (25 ± 3 years old) were instructed to chew gum jelly with a free mastication duration (G100), a half and a quarter duration of G100. Masseter and digastric electromyographic (EMG) activity was recorded to assess mastication and swallowing activity, respectively. In addition, the acceleration of the thyroid cartilage ridge was measured with an accelerometer. The root mean square (RMS) of muscle EMG activity in the masseter and digastric muscles, the number of masseter EMG bursts, time to peak and total duration of each masseter EMG burst, swallowing duration and laryngeal elevation latency were analysed. RESULTS: Restricting masticatory duration reduced the number of mastication cycles (p < .001), prolonged the time to peak (p < .001) and total duration of masseter EMG bursts (p < .001) and resulted in an overall increased RMS score of masseter muscle activity (p = .017). Furthermore, restricted masticatory duration led to a decrease in both swallowing duration (p = .001) and laryngeal elevation latency (p = .012), with a significant increase in the RMS score of digastric muscle activity (p < .001). CONCLUSIONS: Under the experimental conditions of restricted mastication, several adaptation features were observed, including changes in masticatory cycle characteristics and swallowing duration. Thus, although the overall masticatory efficiency was reduced, these adaptations allowed healthy individuals to still swallow safely.
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BACKGROUND: Although biofeedback with contingent electrical stimulation (CES) has demonstrated the reduction effect on sleep bruxism (SB), the relationship between the actual applied CES intensity and efficacy remains uncertain. OBJECTIVE: This study aimed to investigate whether the reduction of bruxism events and jaw muscle symptoms could vary according to the intensity of CES and in probable sleep bruxers. METHODS: Twenty probable sleep bruxers were initially screened for bruxer confirmation based on a 2-week recording of SB events with a portable electromyography recorder (BUTLER®GrindCare®, GC4). A 3-week recording was conducted without CES using a GC4, followed by another 3-week recording with CES. At baseline and before and after the CES (+) session, clinical muscle symptoms were assessed using a 0-10 numerical rating scale (NRS). The relationships between the actual applied CES intensity and the number of SB events/hour, as well as the NRS of clinical muscle symptoms, were analysed. RESULTS: The actual applied CES intensity was positively correlated with the reduction rate of the number of SB events/hour (R = .643, p = .002), as well as with the reduction rate of NRS for pain, unpleasantness, fatigue, tension and stiffness (R > .500, p < .011). CONCLUSION: Higher CES elicited a more robust reduction in SB events and clinical muscle symptoms, in probable bruxers. Prior to selecting CES biofeedback as a management option for SB, it would be beneficial to assess the tolerance threshold of CES in each bruxer in order to predict the effectiveness of CES in probable sleep bruxers.
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Terapia por Estimulación Eléctrica , Electromiografía , Bruxismo del Sueño , Humanos , Bruxismo del Sueño/terapia , Bruxismo del Sueño/fisiopatología , Bruxismo del Sueño/complicaciones , Masculino , Femenino , Adulto , Terapia por Estimulación Eléctrica/métodos , Resultado del Tratamiento , Adulto Joven , Biorretroalimentación Psicológica/métodosRESUMEN
Objectives: Cardiac rehabilitation (CR) is a class I recommendation in the treatment guidelines for cardiovascular disease; however, its postoperative prognostic effects after surgery are not fully understood. Therefore, this study aimed to examine the effect of multidisciplinary outpatient CR on postdischarge all-cause mortality in patients who underwent cardiovascular surgery. Methods: This retrospective cohort study included consecutive patients who underwent elective cardiovascular surgery between April 2015 and March 2021. Patients were categorized into CR and non-CR groups. The primary outcome measure was all-cause mortality. Propensity score-matching analysis was performed to minimize selection bias and differences in clinical characteristics. The propensity score for each patient was produced using logistic regression analysis, with the CR group and the subsequent 27 variables as the dependent and independent variables, respectively. Results: In our cohort (n = 1095), 51 patients (4.7%) died during the follow-up period (mean, 1042 days). The CR group had a significantly lower mortality rate than the non-CR group (hazard ratio, 0.45; 95% CI, 0.21-0.95; P = .036). After propensity score matching adjusted for confounders, the association between CR and reduced risk of all-cause mortality remained (hazard ratio, 0.35; 95% CI, 0.14-0.85; P = .02). Conclusions: Postdischarge multidisciplinary outpatient CR in patients who underwent cardiovascular surgery was associated with a substantial survival benefit, which persisted after adjusting for variables, including age, operative factors, physical and cognitive functions, and nutritional status.
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Background: Orofacial pain conditions are complex disorders that involve biological, social, and psychological factors. Temporomandibular Disorders (TMDs) are one of the most common orofacial pain conditions, and our previous literature review indicated that exercise therapy has shown promise in reducing TMD-related pain. However, more evidence is needed to firmly establish its effectiveness. Objectives: This systematic review aims to investigate the effectiveness of exercise therapy on pain relief and jaw mobility in patients with pain-related TMDs. Methods: To include randomized controlled trials (RCTs) written in English, a literature search was performed using PubMed, Scopus, Web of Science, Cochrane Library, Ovid, EBM reviews, and Academic Search Complete initially from 4th November 2020 until March 2022. A PICOS for this review was as follows; P: Patients with TMD myalgia or arthralgia, I: Excursion exercise, Stretch exercises, Resistance exercise, or Coordination exercise, C: No treatment or education only. O: Pain intensity and Range of Motion (ROM), S: RCTs. After title screening, a full-text assessment was done to extract data. According to Risk of Bias (RoB) 2.0, risk of bias was assessed in each included paper by 2 reviewers independently. Results: A total of 3,388 titles were identified from the electronic database search. After the screening and full-text evaluation, only 5 studies (145 participants) were eligible to be included. Among the exercise modalities, coordination exercise showed a significant effect on pain relief and improvement of joint mobility. Discussion: Due to the heterogeneity and small sample size of the included studies, a meta-analysis was not feasible. However, this systematic review suggested that exercise therapy, especially coordinate exercise, can be effective in managing painful TMD conditions. Further research is needed to establish optimal parameters for this patient population, as well as standardization and consistency in terminology and treatment structure.
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In the treatment of head and neck cancer, cisplatin is often used as a therapeutic agent; however, its efficacy is limited and it can cause renal dysfunction as an adverse effect. For this reason, the use of cisplatin is limited in elderly patients with reduced renal function. Recently, artemisinin, which was developed as an antimalarial drug, was found to have antitumor effects and is effective in combination with other anticancer drugs. In the present study, the antitumor effects of artemisinin and its derivatives as well as their combination with cisplatin and iron on head and neck squamous cell carcinoma cell lines, were investigated. Cell viability was determined by a cell viability assay, the cell cycle was analyzed by flow cytometry, cell death was assessed with annexin V and propidium iodide staining, and western blotting was used to analyze retinoblastoma protein (Rb), phosphorylated (p)Rb, and other cell cycleassociated molecules. A total of four artemisinin compounds were examined and it was found that artesunate and dihydroartemisinin had a significant inhibitory effect on growth. It was also identified that the combination of artesunate, cisplatin, and iron inhibited cell proliferation and caused S/G2M cell cycle arrest. In addition, western blotting of Rb, a molecule involved in the cell cycle, showed that artesunate induced the loss of not only Rb but also pRb. These results suggested that artesunate is a useful drug in combination with cisplatin.
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Artemisininas , Neoplasias de Cabeza y Cuello , Humanos , Anciano , Cisplatino/farmacología , Artesunato/farmacología , Carcinoma de Células Escamosas de Cabeza y Cuello , Proliferación Celular , Artemisininas/farmacología , Ciclo Celular , Apoptosis , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , HierroRESUMEN
BACKGROUND: Treatment for malocclusion can cause discomfort and pain in the teeth and periodontium, which may impair masticatory efficiency. The glucose concentration method is widely used to assess masticatory efficiency for its convenience in the clinical situation, although its validity has not been shown. OBJECTIVES: The aims were to determine the validity of the glucose concentration method and investigate if this method can be applicable to orthodontic patients with braces. METHOD: Sixteen healthy individuals (7 men, 9 women, and 26 ± 5 years old) and 16 patients with malocclusions needing orthodontic treatment (5 men, 11 women, and 26 ± 4 years old) participated. Glucose concentration was measured after 5-, 10-, and 15-s mastication of gummy jelly and compared to Hue values obtained from the color-changing gum method (reference method). In addition, all participants were asked to fill out the Oral Health Impact Profile questionnaire (OHIP) to assess differences in perception related to the mouth before and after the placement of braces. RESULTS: Glucose concentrations were strongly correlated to measures of the two-color chewing gum methods (R2 = 0.965). Both the glucose extraction and chewing gum hue value were the smallest for 5 s chewing cycles and increased as the number of chewing strokes increased for the 15 s chewing cycles. (Hue: R² = 0.510, p < 0.001; glucose: R² = 0.711, p < 0.001) Masticatory efficiency assessed by both methods was significantly lower in orthodontic patients compared to controls (p < 0.05), even though it was not affected by bonding (p > 0.09). In addition, OHIP scores in physical pain dimension and psychological disability were higher in orthodontic patients than in the control group (p < 0.005). CONCLUSION: Measurement of glucose concentration was confirmed as a reliable and convenient method for assessing masticatory efficiency. Furthermore, it appears that this method is applicable to patients with braces whose perception in the oral cavity could change.
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Goma de Mascar , Dolor , Adulto , Color , Femenino , Glucosa , Humanos , Masculino , Masticación , Adulto JovenRESUMEN
BACKGROUND: Maintaining quality of life of elderly denture wearers is one of the most crucial tasks for dentists in the super-aged society. Although external mechanical load on removable dentures has been investigated to minimise a risk of soreness caused by dentures, sensory perception of the alveolar mucosa remains obscure. OBJECTIVES: This study aimed to investigate effect of ageing and tooth loss in sensory function on the alveolar mucosa for deep understanding of the characteristics of pain sensitivity in edentulous individuals. METHODS: Eighteen edentulous participants (ED), as well as 18 age-matched dentate participants (EC) and 18 young dentate participants (YC), participated in this study. Tactile detection threshold (TDT) and pain threshold (PT) were measured with von Frey filaments (0.125-512 mN). Mechanical pain sensitivity (MPS) after a 2-sec application of 1 kg palpation was assessed with a 0-50-100 Numerical Rating Scale (NRS) (0: no pain, 50: slight pain and 100: the worst pain imaginable). Furthermore, entropy scores of TDT, PT and NRS on MPS were calculated. RESULTS: In both maxilla and mandible, EC showed significantly higher TDT and PT, compared with YC, whereas ED showed significantly lower TDT and PT, compared with EC. NRS on MPS in ED was significantly higher than that in EC. The entropy scores of all the outcome parameters showed no significant difference between groups. CONCLUSION: Both ageing and tooth loss can alter tactile and pain perception in the oral mucosa. This suggests that it might be beneficial to assess sensory function of the alveolar mucosa in edentulous patients clinically in prior to denture fabrication.
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Pérdida de Diente , Anciano , Envejecimiento , Dentadura Completa , Humanos , Mucosa Bucal , Umbral del Dolor , Calidad de VidaRESUMEN
Nocifensive behavior induced by injection of glutamate or nerve growth factor (NGF) into rats masseter muscle is mediated, in part, through the activation of peripheral NMDA receptors. However, information is lacking about the mechanism that contributes to pain and sensitization induced by these substances in humans. Immunohistochemical analysis of microbiopsies obtained from human masseter muscle was used to investigate if injection of glutamate into the NGF-sensitized masseter muscle alters the density or expression of the NMDA receptor subtype 2B (NR2B) or NGF by putative sensory afferent (that express SP) fibers. The relationship between expression and pain characteristics was also examined. NGF and glutamate administration increased the density and expression of NR2B and NGF by muscle putative sensory afferent fibers (P < 0.050). This increase in expression was greater in women than in men (P < 0.050). Expression of NR2B receptors by putative sensory afferent fibers was positively correlated with pain characteristics. Results suggest that increased expression of peripheral NMDA receptors partly contributes to the increased pain and sensitivity induced by intramuscular injection of NGF and glutamate in healthy humans; a model of myofascial temporomandibular disorder (TMD) pain. Whether a similar increase in peripheral NMDA expression occurs in patients with painful TMDs warrants further investigation.
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Músculo Masetero , Sustancia P , Animales , Estimulación Eléctrica , Ácido Glutámico/metabolismo , Masculino , Factor de Crecimiento Nervioso , Nociceptores/metabolismo , Umbral del Dolor , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Sustancia P/metabolismoRESUMEN
Myasthenia Gravis (MG) is characterised by muscle weakness and increased fatigability. The aim of this pilot study was to investigate if patients with MG demonstrate different functional chewing patterns and report more complaints related to mastication as compared with healthy controls. Twelve patients (median 60 years Q1-Q3: 46-70) with generalised MG and nine healthy controls (median 57 years Q1-Q3: 55-63) participated. All participants underwent dental and oral examination and were asked to fill in a questionnaire concerning oral health. Static maximum bite force was measured with a bite force transducer, electromyography in the masseter, temporalis, and suprahyoid muscles were recorded, and jaw movement was tracked, during a 5-minute gum chewing test. The patients had more oral complaints (oral health impact profile total score 22.6 vs 7.5 P < 0.01) and had lower peak bite force than controls (18.8kgf (11.1;26.4) (95% CI) vs 29.5 kgf (21.6; 37.4) (P = 0.04)). In contrast, fatigability of the masticatory muscles, as defined by number of chewing cycles during the gum-chewing test, did not differ between patients and controls (P = 0.10). In conclusion, patients had more oral complaints and lower bite force than controls, but did not show significantly different functional chewing patterns. Future studies should aim at integrating measurement of peak force into functional tests. Attention should be given to oral complaints of patients with MG.
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The neurophysiological mechanisms underlying NGF-induced masseter muscle sensitization and sex-related differences in its effect are not well understood in humans. Therefore, this longitudinal cohort study aimed to investigate the effect of NGF injection on the density and expression of substance P, NMDA-receptors and NGF by the nerve fibers in the human masseter muscle, to correlate expression with pain characteristics, and to determine any possible sex-related differences in these effects of NGF. The magnitude of NGF-induced mechanical sensitization and pain during oral function was significantly greater in women than in men (P < 0.050). Significant positive correlations were found between nerve fiber expression of NMDA-receptors and peak pain intensity (rs = 0.620, P = 0.048), and expression of NMDA-receptors by putative nociceptors and change in temporal summation pain after glutamate injection (rs = 0.561, P = 0.003). In women, there was a significant inverse relationship between the degree of NGF-induced mechanical sensitization and the change in nerve fiber expression of NMDA-receptors alone (rs = - 0.659, P = 0.013), and in combination with NGF (rs = - 0.764, P = 0.001). In conclusion, women displayed a greater magnitude of NGF-induced mechanical sensitization that also was associated with nerve fibers expression of NMDA-receptors, when compared to men. The present findings suggest that, in women, increased peripheral NMDA-receptor expression could be associated with masseter muscle pain sensitivity.
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Ácido Glutámico/farmacología , Voluntarios Sanos , Inyecciones , Músculo Masetero/efectos de los fármacos , Factor de Crecimiento Nervioso/farmacología , Caracteres Sexuales , Adulto , Biomarcadores/metabolismo , Tejido Conectivo/metabolismo , Femenino , Humanos , Masculino , Masticación , Células Musculares/efectos de los fármacos , Células Musculares/metabolismo , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/metabolismo , Dolor/patología , Umbral del Dolor/efectos de los fármacos , Presión , Receptores de N-Metil-D-Aspartato/metabolismo , Sustancia P/metabolismo , Factores de TiempoRESUMEN
STUDY OBJECTIVES: This study aims to investigate whether the use of a mandibular advancement device (MAD) is associated with neuroplasticity in corticomotor control of tongue and jaw muscles. METHODS: Eighteen healthy individuals participated in a randomized crossover study with 3 conditions for 2 weeks each: baseline, wearing an oral appliance (sham MAD), or MAD during sleep. The custom-made MAD was constructed by positioning the mandible to 50% of its maximal protrusion limit. Transcranial magnetic stimulation was applied to elicit motor-evoked potentials (MEPs). The MEPs were assessed by constructing stimulus-response curves at 4 stimulus intensities: 90%, 100%, 120%, and 160% of the motor threshold from the right tongue and right masseter and the first dorsal interosseous muscles (control) at baseline, after the first and the second intervention. RESULTS: There was a significant effect of condition and stimulus intensity both on the tongue and on masseter MEPs (P < .01). Tongue and masseter MEPs were significantly higher at 120% and 160% after the MAD compared with the oral appliance (P < .05). There were no effects of condition on first dorsal interosseous muscle MEPs (P = .855). CONCLUSIONS: The finding suggests that MAD induces neuroplasticity in the corticomotor pathway of the tongue and jaw muscles associated with the new jaw position. Further investigations are required in patients with obstructive sleep apnea to see whether this cortical neuroplasticity may contribute or perhaps predict treatment effects with MADs in obstructive sleep apnea. CITATION: Matsuzaki S, Shimada A, Tanaka J, et al. Effect of mandibular advancement device on plasticity in corticomotor control of tongue and jaw muscles. J Clin Sleep Med. 2021;17(9):1805-1813.
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Avance Mandibular , Corteza Motora , Estudios Cruzados , Electromiografía , Humanos , Músculo Masetero , Ferulas Oclusales , LenguaRESUMEN
Pluripotent stem cells (PSCs), embryonic stem cells (ESCs), and induced PSCs (iPSCs) are excellent tools for studying embryonic development in organisms and classified into naïve and primed states. ESC-derived germline chimera individuals can be produced by injecting naïve ESCs/iPSCs into preimplantation embryos, and conversion of primed human ESCs/iPSCs into a naïve state provides insights into epiblast cell features. Non-human ESCs/iPSCs are alternatives to human naïve ESCs/iPSCs, which elicit ethical issues. In this study, we used the common marmoset (Callithrix jacchus) as an animal model. Since 1996, 16 marmoset ESC lines have been established. Because most of these ESC lines are female and were derived >10 years ago, new ESCs, particularly male marmoset ESC lines, are needed. Here, we successfully established 17 novel marmoset ESC lines, including six male ESC lines from in vitro-fertilized (IVF) embryos and 12 ESC lines under feeder-free conditions. This report is the first to establish ESC lines using feeder-free conditions and IVF preimplantation blastocysts in marmosets, and these novel ESC lines could potentially facilitate future non-human primate ESC studies.
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Callithrix , Técnicas de Cultivo de Célula , Animales , Diferenciación Celular , Línea Celular , Células Madre Embrionarias , Femenino , Masculino , EmbarazoRESUMEN
BACKGROUND: In skeletal muscle, free nerve endings are mostly located within the connective tissue. However, the distribution of sensory afferent fibres in healthy human masseter muscle tissues has not been studied. OBJECTIVES: Primarily to investigate human masseter muscle nerve fibre densities as well as expression of NR2B receptors, substance P (SP) and nerve growth factor (NGF), and secondarily to compare this between a) nerve fibres associated with myocytes and within connective tissue; b) sexes; and c) ages. METHODS: Microbiopsies of the masseter muscle were obtained from 60 sex- and age-matched healthy participants. Biopsy sections were analysed using immunohistochemistry and were visualised with a Leica TCS SPE confocal microscope. The Mann-Whitney U test was used for statistical analyses. RESULTS: The density of nerve fibres within connective tissue was significantly greater than in nerve fibres associated with myocytes (P < .001). Nerve fibres within connective tissue expressed SP alone or together with NR2B significantly more often than those associated with myocytes (P < .001). The frequency of nerve fibres, which expressed SP alone or in combination with NR2B or NGF, was significantly greater in women than in men (P < .050). Moreover, the co-expression of the three markers together was inversely correlated with age in women (P < .002). CONCLUSIONS: There is a higher density and greater expression of sensory nerve fibres within the connective tissue than associated with myocytes in healthy human masseter muscle. This suggests that nerve fibres within connective tissue are more involved in nociception than nerve fibres associated with myocytes.
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Músculo Masetero , Sustancia P , Femenino , Humanos , Masculino , Músculo Esquelético , Fibras Nerviosas , Factor de Crecimiento NerviosoRESUMEN
Dentists stand in an optimal position to prevent and manage patients suffering from chronic orofacial pain (OFP) disorders, such as temporomandibular disorders, burning mouth syndrome, trigeminal neuralgia, persistent idiopathic dentoalveolar pain, among others. However, there are consistent reports highlighting a lack of knowledge and confidence in diagnosing and treating OFP among dental students, recent graduates, and trained dentists, which leads to misdiagnosis, unnecessary costs, delay in appropriate care and possible harm to patients. Education in OFP is necessary to improve the quality of general dental care and reduce individual and societal burden of chronic pain through prevention and improved quality of life for OFP patients. Our aims are to emphasize the goals of OFP education, to identify barriers for its implementation, and to suggest possible avenues to improve OFP education in general, postgraduate, and continuing dental education levels, including proposed minimum OFP competencies for all dentists. Moreover, patient perspectives are also incorporated, including a testimony from a person with OFP. General dentists, OFP experts, educators, researchers, patients, and policy makers need to combine efforts in order to successfully address the urgent need for quality OFP education.
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Dolor Crónico , Dolor Crónico/terapia , Competencia Clínica , Dolor Facial/terapia , Humanos , Atención al Paciente , Calidad de VidaRESUMEN
Numerous studies have confirmed the effectiveness of cognitive behavioral therapy (CBT) for chronic pain, and it is generally regarded as an appropriate intervention. However, it may not be effective for some pain sites, and the duration of the effect may be limited. In addition, some studies of CBT lacked a comparison group. This review summarizes evidence for the effectiveness of CBT for orofacial pain and assists in the development of guidelines for orofacial pain management. A literature search in PubMed was performed for studies published from April 1990 through March 2020. The search keywords were "burning mouth syndrome," "temporomandibular disorders," "myofascial pain syndrome,""chronic orofacial pain conditions," "cognitive behavioral therapy," and "non-pharmacological therapy." The results indicate that CBT alone or in combination with other treatments, such as intraoral appliance, stress management, or biofeedback, is effective for the vast majority of orofacial pain cases. Therefore, dentists should consider using CBT to manage orofacial pain in their patients.
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Síndrome de Boca Ardiente , Terapia Cognitivo-Conductual , Trastornos de la Articulación Temporomandibular , Dolor Facial/terapia , Humanos , Manejo del DolorRESUMEN
This study investigated the effect of a repeated and standardized jaw protrusion training (JPT) task on corticomotor excitability as assessed by motor evoked potentials (MEPs) in masseter and tongue muscle with the use of transcranial magnetic stimulation (TMS). Sixteen healthy participants performed three series of a standardized JPT task on three consecutive days. Each day participants performed 41-min of JPT consisting of three series. In all series, participants were instructed to target 50% and 100% of the maximum jaw protrusion positions. In the first and third series without any feedback but during the second series, participants were provided a custom-made mandibular advancement device to help achieve the correct protruded position. Single pulse TMS was applied to elicit MEPs from right masseter, right tongue and right first dorsal interosseous muscles (FDI) (as control), pre and post-task on Day-1 and -3. Masseter MEPs and tongue MEPs were significantly dependent on stimulus intensity (P < 0.001) and on task session (P < 0.001). Amplitude of masseter and tongue MEPs at post-task Day-3 were significantly higher compared to baseline values (pre-task Day-1) (P < 0.005). FDI MEPs were dependent on stimulus intensity only (P < 0.001) but not on task session (P = 0.677). Our novel findings suggest that participants performing an active and repeated JPT task demonstrate neuroplasticity in terms of increased corticomotor excitability not only in masseter muscles but also in tongue muscles. This finding may have implications for patients with obstructive sleep apnea treated by a mandibular advancement device where the lower jaw is passively held in a protruded position.
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Potenciales Evocados Motores/fisiología , Músculo Masetero/fisiología , Corteza Motora/fisiología , Plasticidad Neuronal/fisiología , Apnea Obstructiva del Sueño/terapia , Lengua/fisiología , Adulto , Electromiografía , Femenino , Humanos , Masculino , Estimulación Magnética Transcraneal , Adulto JovenRESUMEN
Seasonal changes in the environment lead to depression-like behaviors in humans and animals. The underlying mechanisms, however, are unknown. We observed decreased sociability and increased anxiety-like behavior in medaka fish exposed to winter-like conditions. Whole brain metabolomic analysis revealed seasonal changes in 68 metabolites, including neurotransmitters and antioxidants associated with depression. Transcriptome analysis identified 3,306 differentially expressed transcripts, including inflammatory markers, melanopsins, and circadian clock genes. Further analyses revealed seasonal changes in multiple signaling pathways implicated in depression, including the nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway. A broad-spectrum chemical screen revealed that celastrol (a traditional Chinese medicine) uniquely reversed winter behavior. NRF2 is a celastrol target expressed in the habenula (HB), known to play a critical role in the pathophysiology of depression. Another NRF2 chemical activator phenocopied these effects, and an NRF2 mutant showed decreased sociability. Our study provides important insights into winter depression and offers potential therapeutic targets involving NRF2.
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Conducta Animal/fisiología , Depresión/metabolismo , Regulación de la Expresión Génica/fisiología , Factor 2 Relacionado con NF-E2/metabolismo , Oryzias/fisiología , Estaciones del Año , Animales , Dimetilsulfóxido/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Genoma , Mutación , Factor 2 Relacionado con NF-E2/genéticaRESUMEN
Background: Glutamate, as well as nerve growth factor (NGF), is involved in nociception from peripheral tissues, such as muscles. However, the potential interaction between glutamate and NGF still remains unclear. This study investigated the interaction between glutamate-induced masseter muscle pain and NGF-induced allodynia on pain perception and jaw function in healthy individuals, and any possible sex differences in the response. Materials and Methods: Thirty pain-free adult participants (15 men and 15 women, mean age ± SD: 24 ± 4 years) participated in this study consisting of three sessions (Day 0, Day 3, and Day 4). NGF (5 µg/mL, 1.0 mL) was injected into the masseter muscle on Day 0 to induce muscle allodynia. On Day 3, glutamate (1M, 0.2 mL) was injected into the same masseter muscle. Before and after injections on Day 0 and 3, and post-injection (Day 4), spontaneous pain, temporal summation pain, as well as functional pain and fatigue in response to chewing were assessed with validated scales, and the pressure pain threshold (PPT) was recorded. Results: Spontaneous pain intensity was significantly higher after glutamate than NGF (P < 0.001). PPTs, temporal summation pain and functional measures were all reduced 3 days after NGF injection (P's < 0.001). Injection of glutamate on Day 3 did not further affect PPTs or temporal summation pain and there were no sex differences in the effects (P > 0.189). Chewing pain (P = 0.022) and fatigue increased after glutamate injection to a higher degree in the women than men (P = 0.037). Conclusion: Taken together, while glutamate injected into the NGF-sensitized muscle was painful, it did not alter muscle tenderness in women vs. men. However, pain and fatigue evoked by jaw function were higher in women after glutamate injection. This suggest that sex differences reported for masseter myalgia, mimicked by glutamate and NGF mediated pain in this study, may be greater for measures of perceived jaw function, which should be considered in a clinical evaluation.
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PURPOSE: To investigate if sleep bruxism (SB) influences training-induced cortical plasticity and performance in terms of accuracy and precision of a tooth-clenching task (TCT). METHODS: Thirty-eight participants were allocated into SB group (N=19) and control group (N=19) according to presence of SB based on a 2-week screening. The participants were instructed to perform a standardized TCT for 58min at three different force levels (10%, 20% and 40% of maximum voluntary contraction; MVC) in three series (first and third without visual-feedback and second with visual-feedback). Accuracy and precision of the TCT were calculated from actual bite force values. Transcranial magnetic stimulation was applied to elicit motor evoked potentials (MEPs) from the masseter and first dorsal interosseous muscle (FDI) before the TCT (pre-TCT-session) and 5-min after the TCT (post-TCT-session). RESULTS: Accuracy was significantly dependent on the series and target force level (P<0.001), however, there was a significant decrease only in the control group at 10% MVC from first to third session (P<0.001). No significant differences between groups were observed for the precision of the TCT. Masseter MEPs in the SB group in the pre-TCT-session at 120% and 160% motor threshold were significantly lower than in the control group (P<0.05). Masseter MEPs of the control group in the post-TCT-session were significantly higher than the pre-TCT-session (P<0.05) but not SB. FDI MEPs were only dependent on stimulus intensity (P<0.001). CONCLUSIONS: SB is associated with significant changes not only in excitability of corticomotor control but also motor learning of jaw movements and force control.
Asunto(s)
Bruxismo del Sueño , Electromiografía , Potenciales Evocados Motores , Humanos , Músculo Masetero , Músculo Esquelético , Estimulación Magnética TranscranealRESUMEN
OBJECTIVES: Sleep bruxism (SB), characterized by repetitive jaw-muscle activity during sleep, is often suggested as a cause of temporomandibular disorders (TMD), orofacial pain, and headache. This study aimed to challenge the relationship between jaw-muscle electromyographic (EMG) activity during sleep and jaw muscle symptoms including pain by modulation of the levels of EMG activity. Contingent electrical stimulation (CES) using a portable single-channel EMG device was applied at different stimulus intensities to inhibit jaw muscle activity. MATERIALS AND METHODS: Sixty probable sleep-bruxers, screened and confirmed by a 2-week use of a portable EMG device, were randomly allocated into one of 3 groups (High/Low/Placebo CES). At baseline and after 2 weeks CES intervention, the participants were asked to score pain intensity, as well as unpleasantness, fatigue, tension, soreness and stiffness in their jaw muscles, on 0-10 numerical rating scales (NRS). RESULTS: Only in the High CES group, the number of EMG events/hour was significantly decreased (P = 0.024). Although the NRS scores of pain did not change, interestingly the NRS scores of unpleasantness (P = 0.037), tension (P < 0.001) and soreness (P = 0.004) in the High CES group and tiredness (P = 0.002) and soreness (P = 0.006) in the Low CES group were significantly decreased after the CES intervention compared to baseline. CONCLUSION: High intensity CES demonstrated inhibitory effect on masticatory muscle EMG activity during sleep and was associated with significant decreases in jaw muscle symptoms (unpleasantness/tiredness/soreness) but not pain responses. These findings challenge the traditional concept that probable sleep bruxism is directly related to pain but appears related to more unspecific muscle symptoms.