Mana Hasegawa

Background/Objectives: Regular physical exercise conditioning attenuates nociceptive responses. However, it remains unclear whether physical exercise performed before local inflammation exerts prolonged preventive effects. This study determined whether treadmill run (TR) preconditioning produces sustained preventive effects on craniofacial nociception and associated brain responses following persistent craniofacial inflammation. Methods: Male C57BL/6J mice were assigned to sedentary or TR groups. Daily TR conditioning was performed for 10 days before masseter muscle injection of complete Freund’s adjuvant (CFA) on Day 0. Craniofacial-pain- and related anxiety-like behaviors were determined by the orofacial formalin, elevated plus maze, and open-field tests before and 3 (CFA3) or 7 (CFA7) days after CFA injection. Brain responses in the amygdala, insular cortex, hippocampal CA1, and primary motor cortex were assessed using multiple epigenetic- and neural-activity-related markers. Results: Under sedentary conditions, both CFA3 and CFA7 groups showed increased pain- and anxiety-like behaviors and elevated expression of epigenetic- and neural-activity-related markers in most brain regions. TR preconditioning attenuated these behavioral responses even three and seven days after TR cessation and altered the expression of epigenetic markers in several brain regions, although the direction of change varied by region and time point. TR preconditioning consistently reduced the expression of neural activity markers in most brain areas in both the CFA3 and CFA7 groups, with a few exceptions. Conclusions: TR preconditioning exerted prolonged preventive effects on craniofacial-pain-like behaviors and associated brain responses following craniofacial inflammation.

Aims: Dental clinical skills include subtle techniques, such as applying an appropriate amount of force depending on the procedure. This study investigated the training effects of using pressure sensors on force magnitude control during the dental procedure. Methods: Forty-two dental trainees participated in this study. The experimental task was a fit test, assessing the pressure contact of a denture against the mandible. The force applied by each participant was measured using a modified mannequin equipped with a digital force gauge. Fit test training was performed under conditions specifying the presence or absence of fit test material and various degrees of force, with 50 N set as the standard. After training, the ability to control force magnitude was statistically evaluated by examining the error between the specified and actual values. Results: The presence of the fit test material did not affect the force magnitude, and the time required decreased in proportion to the number of trials. Initially, not all participants were able to apply 50 N without special instructions. However, after training, the measured values exceeded 50 N. The error from the target value was significantly larger when 70 N was designated compared to 50 N. Errors between the specified and actual values obtained at 30–60 N exhibited a decreasing trend in each successive cycle. Conclusion: Visualized numerical data are effective for developing practical force control. This form of experiential learning may contribute to the early retention of basic dental skills.

Background/Objectives: Chronic craniofacial inflammation is recognized as a factor in anxiety-like behaviors, yet effective therapeutic options remain limited. Agmatine, a dietary bioactive compound found in fermented foods such as sake lees, exhibits modulatory effects on neural functions, alleviating psychological distress like anxiety associated with local inflammation. Methods: We investigated both the therapeutic and preventive effects of agmatine on anxiety-like behaviors and the related neural basis in a mouse model of persistent craniofacial inflammation induced by complete Freund’s adjuvant (CFA). Results: Comprehensive behavioral assessments, including the elevated plus maze, open field, dark–light box, social interaction, and novel object recognition tests, revealed that therapeutic agmatine administration (1.0 and 30 mg/kg) significantly reduced CFA-induced anxiety-like behaviors, with the higher dose showing more robust and sustained effects across multiple time points. These behavioral improvements were paralleled by reductions in acetylated histone H3, FosB, and c-Fos expression in key anxiety-related brain regions, suggesting a reversal of craniofacial inflammation-associated neural changes. In contrast, preventive agmatine treatment exerted modest and time-dependent behavioral benefits with minimal molecular normalization. Notably, preventive agmatine did not affect general locomotor activity (indicated by total movement distance), indicating that its anxiolytic effects were not confounded by altered locomotor activity. Metabolomic analysis confirmed the presence of agmatine in sake lees (~0.37 mM), supporting the hypothesis that fermented food products might offer dietary routes to emotional resilience. Conclusions: These findings underscore agmatine’s promise as a context-specific epigenetic modulator capable of mitigating anxiety-like behaviors by normalizing inflammation-driven molecular dysregulation in the brain.

Aims: Dental procedures involve intricate techniques that can be challenging to visualize, often hindering imitation and assessment. In this study, the impression-taking performance of abutment teeth was quantitatively analyzed to create objective indexes for dental skill education. Methods: Participants were divided into two groups of different clinical experience levels: 10 dentists and 10 dental students. An aluminum model of abutment teeth was employed to simplify the experiment. An optical motion capture system (VICON, Oxford, UK) measured participants’ movements. The impression accuracy, time length on the analyzed section, impression material pouring speed, total amount of impression material used, and syringe tip trajectory were evaluated. Fisher’s exact test and Mann–Whitney U test were used to compare the two groups’ results (?=0.05). Results: In the dentist group, there were few apparent failures and a high impression accuracy. The amount of impression material dispensed tended to be larger in the dentist group, with longer practice time and slower syringe movement speed. This suggested that the inexperienced participants were sufficiently unable to pour out the impression material. The syringe tip trajectories were not significantly different between the groups. An instructor’s advice is often limited to abstract feedback; therefore, specific suggestions might assist in effective skill education. Conclusion: It is possible to quantitatively analyze impression-taking performance and provide helpful information for dental skill education by using this system.

This narrative review provides an overview of current knowledge on the impact of nutritional strategies on chronic craniofacial pain associated with temporomandibular disorders (TMDs). Individuals experiencing painful TMDs alter their dietary habits, avoiding certain foods, possibly due to chewing difficulties, which might lead to nutrient deficiencies. Our literature investigation revealed that the causal links between nutritional changes and craniofacial pain remain unclear. However, clinical and preclinical studies suggest that nutraceuticals, including vitamins, minerals, polyphenols, omega-3 fatty acids, isoprenoids, carotenoids, lectins, polysaccharides, glucosamines, and palmitoylethanolamides, could have beneficial effects on managing TMDs. This is described in 12 clinical and 38 preclinical articles since 2000. Clinical articles discussed the roles of vitamins, minerals, glucosamine, and palmitoylethanolamides. The other nutraceuticals were assessed solely in preclinical studies, using TMD models, mostly craniofacial inflammatory rodents, with 36 of the 38 articles published since 2013. Our investigation indicates that current evidence is insufficient to assess the efficacy of these nutraceuticals. However, the existing data suggest potential for therapeutic intervention in TMDs. Further support from longitudinal and randomized controlled studies and well-designed preclinical investigations is necessary to evaluate the efficacy of each nutraceutical intervention and understand their underlying mechanisms in TMDs.

This study determined the effect of daily administration of Rice-koji on anxiety and nociception in mice subjected to repeated forced swim stress (FST). In a parallel experiment, it was determined whether ergothioneine (EGT) contained in Rice-koji displayed similar effects. Anxiety and nociception were assessed behaviorally using multiple procedures. c-Fos and FosB immunoreactivities were quantified to assess the effect of both treatments on neural responses in the paraventricular nucleus of the hypothalamus (PVN), nucleus raphe magnus (NRM), and lumbar spinal dorsal horn (DH). FST increased anxiety- and pain-like behaviors in the hindpaw. Rice-koji or EGT significantly prevented these behaviors after FST. In the absence of formalin, both treatments prevented decreased FosB expressions in the PVN after FST, while no effect was seen in the NRM and DH. In the presence of formalin, both treatments prevented changes in c-Fos and FosB expressions in all areas in FST mice. Further, in vitro experiments using SH-SY5Y cells were conducted. Rice-koji and EGT did not affect cell viability but changed the level of brain-derived neurotrophic factor. In conclusion, Rice-koji could reduce anxiety and pain associated with psychophysical stress, possibly mediated by the modulatory effects of EGT on neural functions in the brain.

The conditions of stress contagion are induced in bystanders without direct experiences of stressful events. This study determined the effects of stress contagion on masseter muscle nociception in mice. Stress contagion was developed in the bystanders after cohabitating with a conspecific mouse subjected to social defeat stress for 10 days. On Day 11, stress contagion increased anxiety‐ and orofacial inflammatory pain‐like behaviors. The c‐Fos and FosB immunoreactivities evoked by masseter muscle stimulation were increased in the upper cervical spinal cord, while c‐Fos expressions were increased in the rostral ventromedial medulla, including the lateral paragigantocellular reticular nucleus and nucleus raphe magnus in stress contagion mice. The level of serotonin in the rostral ventromedial medulla was increased under stress contagion, while the number of serotonin positive cells was increased in the lateral paragigantocellular reticular nucleus. Stress contagion increased c‐Fos and FosB expressions in the anterior cingulate cortex and insular cortex, both of which were positively correlated with orofacial inflammatory pain‐like behaviors. The level of brain‐derived neurotrophic factor was increased in the insular cortex under stress contagion. These results indicate that stress contagion can cause neural changes in the brain, resulting in increased masseter muscle nociception, as seen in social defeat stress mice.

We investigated the effects of social defeat stress (SDS) and treadmill running on masseter muscle nociception, which was quantified by the orofacial formalin test and c‐Fos and FosB immunoreactivities in the upper cervical spinal cord (C1/C2) region in male mice. After daily SDS or non‐SDS conditioning for 10 days, SDS‐conditioned mice were categorized into SDS‐susceptible versus resilient mice. Several mice, including non‐SDS‐conditioned, SDS‐susceptible, and resilient mice, were selected to assess masseter muscle nociception on Day 11. SDS conditioning for 10 days increased masseter muscle‐evoked nocifensive behaviors and c‐Fos and FosB expression in SDS‐susceptible compared to non‐SDS and resilient mice. The remaining SDS‐susceptible and non‐SDS mice were subjected to an additional 10 days of SDS plus treadmill running or sedentary sessions before assessing masseter muscle nociception on Day 21. Daily treadmill running sessions reduced enhanced masseter muscle nociception in SDS‐susceptible mice but not in non‐SDS mice. The preventive effects of daily treadmill running immediately after each SDS conditioning for 10 days on orofacial nocifensive behaviors were assessed on Day 11. Treadmill running conducted immediately after daily SDS inhibited enhanced orofacial nocifensive behaviors. These findings indicate that repeated SDS increases masseter muscle nociception, which could be prevented by daily treadmill running exercise.