Elucidation of neuronal activity in mouse models of TMJ injury by in vivo GCaMP Ca 2+ imaging of intact trigeminal ganglion neurons.

Patients with temporomandibular disorders (TMD) typically experience facial pain and discomfort or tenderness in the temporomandibular joint (TMJ), causing disability in daily life. Unfortunately, existing treatments for TMD are not always effective, creating a need for more advanced, mechanism-based therapies. In this study, we used in vivo GCaMP3 Ca 2+ imaging of intact trigeminal ganglia (TG) to characterize functional activity of the TG neurons in vivo , specifically in TMJ animal models. This system allows us to observe neuronal activity in intact anatomical, physiological, and clinical conditions and to assess neuronal function and response to various stimuli. We observed a significant increase in spontaneously and transiently activated neurons responding to mechanical, thermal, and chemical stimuli in the TG of forced mouth open (FMO) mice. An inhibitor of the CGRP receptor significantly attenuated FMO-induced facial hypersensitivity. In addition, we confirmed the attenuating effect of CGRP antagonist on FMO-induced sensitization by in vivo GCaMP3 Ca 2+ imaging of intact TG. Our results contribute to unraveling the role and activity of TG neurons in the TMJ pain animal models of TMD, bringing us closer understanding the pathophysiological processes underlying TMD. Our study also illustrates the utility of in vivo GCaMP3 Ca 2+ imaging of intact TG for studies aimed at developing more targeted and effective treatments for TMD.

Dental Composite Performance Prediction Using Artificial Intelligence.

Objective: There is a need to increase the performance and longevity of dental composites and accelerate the translation of novel composites to the market. This study explores artificial intelligence (AI), specifically machine learning (ML), to predict the performance outcomes (POs) of dental composites from their composite attributes (CAs). Methods: An extensive dataset from over 200 publications was built and refined to 233 samples with 17 CAs and 7 POs. Nine ML models were evaluated for PO prediction performance using classified data, and Five ML models were evaluated for PO regression analysis. Results: The KNN model excelled in predicting flexural modulus (FlexMod), Decision Tree model in flexural strength (FlexStr) and volumetric shrinkage (ShrinkV), and Logistic Regression and SVM models in shrinkage stress (ShrinkStr). Receiver operating characteristic area under the curve (ROC AUC) analysis confirmed these results but found that Random Forest was more effective for FlexStr and ShrinkV, suggesting the possibility of Decision Tree overfitting the data. Regression analysis revealed that the Voting Regressor was superior for FlexMod and ShrinkV predictions, while Decision Tree Regression was optimal for FlexStr and ShrinkStr. Feature importance analysis indicated TEGDMA is a key contributor to FlexMod and ShrinkV, BisGMA and UDMA to FlexStr, and depth of cure, degree of monomer-to-polymer conversion, and filler loading to ShrinkStr. Significance: There is a need to conduct a full analysis using multiple ML models because different models predict different POs better, and for a large, comprehensive dataset to train robust AI models to facilitate the prediction and optimization of composite properties and support the development of new dental materials.

Forced mouth opening induces post-traumatic hyperalgesia and associated peripheral sensitization after temporomandibular joints injury in mice.

Temporomandibular disorder (TMD) is the most prevalent painful condition in the craniofacial area. The pathophysiology of TMD is not fully understood, and it is necessary to understand pathophysiology underlying painful TMD conditions to develop more effective treatment methods. Recent studies suggested that external or intrinsic trauma to TMJ is associated with chronic TMD in patients. Here, we investigated the effects of the TMJ trauma through forced-mouth opening (FMO) in mice to determine pain behaviors and peripheral sensitization of trigeminal nociceptors. FMO increased mechanical hyperalgesia assessed by von Frey test, spontaneous pain-like behaviors assessed by mouse grimace scale, and anxiety-like behaviors assessed by open-field test. In vivo GCaMP Ca 2+ imaging of intact trigeminal ganglia (TG) showed increased spontaneous Ca 2+ activity and mechanical hypersensitivity of TG neurons in the FMO compared to the sham group. Ca 2+ responses evoked by cold, heat, and capsaicin stimuli were also increased. FMO-induced hyperalgesia and neuronal hyperactivities were not sex dependent. TG neurons sensitized following FMO were primarily small to medium-sized nociceptive afferents. Consistently, most TMJ afferents in the TG were small-sized peptidergic neurons expressing calcitonin gene-related peptides, whereas nonpeptidergic TMJ afferents were relatively low. FMO-induced intraneural inflammation in the surrounding tissues of the TMJ indicates potentially novel mechanisms of peripheral sensitization following TMJ injury. These results suggest that the TMJ injury leads to persistent post-traumatic hyperalgesia associated with peripheral sensitization of trigeminal nociceptors.

Elucidation of neuronal activity in mouse models of temporomandibular joint injury and inflammation by in vivo GCaMP Ca2+ imaging of intact trigeminal ganglion neurons.

ABSTRACT: Patients with temporomandibular disorders (TMDs) typically experience facial pain and discomfort or tenderness in the temporomandibular joint (TMJ), causing disability in daily life. Unfortunately, existing treatments for TMD are not always effective, creating a need for more advanced, mechanism-based therapies. In this study, we used in vivo GCaMP3 Ca2+ imaging of intact trigeminal ganglia (TG) to characterize functional activity of the TG neurons in vivo, specifically in mouse models of TMJ injury and inflammation. This system allows us to observe neuronal activity in intact anatomical, physiological, and clinical conditions and to assess neuronal function and response to various stimuli. We observed a significant increase in spontaneously and transiently activated neurons responding to mechanical, thermal, and chemical stimuli in the TG of mice with TMJ injection of complete Freund adjuvant or with forced mouth opening (FMO). An inhibitor of the calcitonin gene-related peptide receptor significantly attenuated FMO-induced facial hypersensitivity. In addition, we confirmed the attenuating effect of calcitonin gene-related peptide antagonist on FMO-induced sensitization by in vivo GCaMP3 Ca2+ imaging of intact TG. Our results contribute to unraveling the role and activity of TG neurons in the TMJ pain, bringing us closer to understanding the pathophysiological processes underlying TMJ pain after TMJ injury. Our study also illustrates the utility of in vivo GCaMP3 Ca2+ imaging of intact TG for studies aimed at developing more targeted and effective treatments for TMJ pain.