Baseline resting-state functional connectivity determines subsequent pain ratings to a tonic ecologically valid experimental model of orofacial pain.

ABSTRACT: Pain is a subjective experience with significant individual differences. Laboratory studies investigating pain thresholds and experimental acute pain have identified structural and functional neural correlates. However, these types of pain stimuli have limited ecological validity to real-life pain experiences. Here, we use an orthodontic procedure-the insertion of an elastomeric separator between teeth-which typically induces mild to moderate pain that peaks within 2 days and lasts several days. We aimed to determine whether the baseline structure and resting-state functional connectivity of key regions along the trigeminal nociceptive and pain modulatory pathways correlate with subsequent peak pain ratings. Twenty-six healthy individuals underwent structural and resting-state functional MRI scanning before the placement of a separator between the first molar and second premolar, which was kept in place for 5 days. Participants recorded pain ratings 3 times daily on a 100-mm visual analogue scale. Peak pain was not significantly correlated with diffusion metrics of the trigeminal nerve or gray matter volume of any brain region. Peak pain did, however, positively correlate with baseline resting-state functional connectivity between the thalamus contralateral to the separator and bilateral insula, and negatively correlated with connectivity between the periaqueductal gray (PAG) and core nodes of the default mode network (medial prefrontal and posterior cingulate cortices). The ascending (thalamic) nociceptive and the descending (PAG) pain modulatory pathways at baseline each explained unique variation in peak pain intensity ratings. In sum, preinterventional functional neural architecture of both systems determined the individual pain experience to a subsequent ecologically valid pain stimulus.

Increased somatosensory amplification is associated with decreased pressure pain thresholds at both trigeminal and extra-trigeminal locations in healthy individuals.

BACKGROUND: The diagnosis of temporomandibular disorders (TMD) is based on patient history and physical examination, and may require medical imaging. Masticatory muscle palpation is essential to make a diagnosis of TMD. However, the response of masticatory muscles to mechanical pressure stimuli depends on many physical and psychological factors. OBJECTIVE: This study aimed at determining the impact of somatosensory amplification (SSA)-an estimate of somatic awareness and bodily hypervigilance-on pressure pain thresholds (PPTs) measured at both trigeminal and extra-trigeminal locations in healthy individuals. METHODS: PPTs were measured at the right anterior temporalis and superficial masseter, and the thenar eminence of the right hand in one hundred healhty individuals (69F, 31M), divided in three groups based on their SSA scores: low (N = 32), intermediate (N = 34) and high (N = 34). General linear models were used to test between-group differences in PPTs including sex as a covariate. The level of significance was set at P < .05. RESULTS: Individuals with high SSA had lower PPTs at the anterior temporalis than individuals with low (P = .006) and intermediate (P = .001) SSA. No significant between-group differences were found in PPTs measured at the masseter (P = .372). PPTs measured at the thenar eminence were significantly lower in the high than the low SSA group (P = .009). Females had lower PPTs at the masseter than males (P = .021) but not at other muscle locations (all P > .05). CONCLUSION: Increased somatosensory amplification is associated with decreased pressure pain thresholds at both trigeminal and extra-trigeminal locations in healthy individuals. SSA could be a potential confounder while diagnosing TMD and evaluating treatment outcomes.

Impact of post-orthodontic dental occlusion on masticatory performance and chewing efficiency.

BACKGROUND: Whether precise orthodontic detailing of occlusion impacts masticatory function is unknown. In this study, we aimed to assess the impact of post-orthodontic dental occlusion on masticatory performance and chewing efficiency. MATERIALS AND METHODS: Fifty-four adults who completed orthodontic treatment were categorized into two groups using the American Board of Orthodontics (ABO) model grading system: one meeting ABO standards (ABO, N = 29), the other failing to meet them (non-ABO, N = 25). The electromyographic (EMG) signals of the anterior temporalis (AT) and superficial masseter muscles were recorded bilaterally during static (clenching) and dynamic (gum chewing) tests. Chewing efficiency was measured by calculating the median particle size (MPS) and broadness of particle distribution (BPD) after five chewing trials of experimental silicone food at a standardized chewing rate. RESULTS: Participants of the ABO group had a slightly more symmetric activation of the AT muscles during clenching (P = 0.016) and chewed a gum at a slower rate (P = 0.030). During the standardized chewing test with silicone food, ABO subjects had slightly greater EMG potentials at all muscle locations than non-ABO individuals (all P < 0.05). MPS and BDP did not differ significantly between groups (all P > 0.05). LIMITATIONS: The severity of the initial malocclusion of the study participants was not in the statistical model as a potential confounder on the outcome measures. CONCLUSIONS: Meeting ABO standards contributes to a slightly more balanced activation of the temporalis muscles during clenching and more efficient muscle recruitment during chewing but does not improve chewing efficiency.

Combinatorial Coarse-Graining of Molecular Dynamics Simulations for Detecting Relationships between Local Configurations and Overall Conformations.

An automatic, multiscale, and three-dimensional (3D) summary of local configurations of the dynamics of proteins can help to discover and describe the relationships between different parts of proteins across spatial scales, including the overall conformation and 3D configurations of side chains and domains. These discoveries can improve our understanding of the function and allosteric mechanism of proteins and could potentially provide an avenue to test and improve the molecular mechanics force fields at different spatial resolutions. Many of the current methods are unable to effectively summarize shapes of 3D local configurations across all spatial scales. Here, we propose frequent substructure clustering (FSC) to fill this gap. Frequent substructure clustering of the Cß atoms of the GB3 protein identifies six clusters of co-occurring local configurations. The clusters that are localized at different regions contribute to the overall conformation, and form two anticorrelating groups. The results suggest that FSC could describe dynamical relationships between different parts of proteins by providing a 3D description of the frequently occurring local configurations at different spatial resolutions. FSC could augment the use of other methods, such as Markov state models, to study the function of subcellular processes and highlight the role of local configurations in biomolecular systems.

Oscillatory Diffusion and Second-Order Cyclostationarity in Alanine Tripeptide from Molecular Dynamics Simulation.

Molecular dynamics (MD) simulation distinctly describes motions of biomolecules at high resolution and can potentially be used to explain allosteric mechanism in subcellular processes. Statistical methods are necessary to realize this potential because MD simulations generate a large volume of data and because the analysis is never efficient, objective, or thorough without using appropriate statistical approaches. Tracing the flow of information within a biomolecule requires not only a description of an overall mechanism but also a multiscale statistical description from atomic interactions to the overall mechanism. The foundation of this multiscale description, in general, is a measure of correlation between motions of atoms or residues, as reflected by dynamic cross-correlation, Pearson correlation, or mutual information. However, these correlations can be inadequate because they assume wide sense stationarity, which means that the instantaneous average and correlation of a particular property are time-independent. Consequently, these measures of correlation cannot account for correlation between motions of different frequencies, since frequency implies oscillation and variation over time. Here, we characterize the nonstationarity in the form of pure oscillatory instantaneous variance in the signed dihedral angular accelerations (SDAA) along the main chain of alanine tripeptide in MD simulations by power spectrum, corrected squared envelope spectrum (CSES), and cross-CSES. This oscillation has a physical interpretation of an oscillatory diffusion. The fraction of this oscillation in all motions is as high as about 40% at some frequencies. This shows that oscillatory instantaneous variance exists in the SDAA and that significant correlation may not be accounted for in current correlation analysis. This oscillation is also found to transmit between dihedral angles. These results could have implications in the understanding of the dynamics of biomolecules.