Intramuscular injection of nerve growth factor as a model of temporomandibular disorder: nature, time-course, and sex differences characterising the pain experience.

Background: Temporomandibular disorder (TMD) is a common condition that frequently transitions to chronic symptoms. Experimental pain models that mimic the symptoms of clinical TMD may be useful in understanding the mechanisms, and sex differences, present in this disorder. Here we aimed to comprehensively characterise the nature and time-course of pain, functional impairment and hyperalgesia induced by repeated intramuscular injection of nerve growth factor (NGF) into the masseter muscle, and to investigate sex differences in the NGF-induced pain experience. Methods: 94 healthy individuals participated in a longitudinal study with 30-day follow-up. NGF was injected into the right masseter muscle on Day 0 and Day 2. Participants attended laboratory sessions to assess pain (Numerical Rating Scale; NRS), functional limitation (mouth opening distance, Jaw Functional Limitation Scale; JFLS) and mechanical sensitization (pressure pain thresholds; PPTs) on Days 0, 2 and 5 and completed twice daily electronic pain dairies from Day 0 to day 30. Results: Peak pain averaged 2.0/10 (95 % CI: 1.6-2.4) at rest and 4.3/10 (95 % CI: 3.9-4.8) on chewing. Pain-free mouth opening distance reduced from 5.0 cm (95 % CI: 4.8-5.1 cm) on Day 0 to 3.7 cm (95 % CI: 3.5-3.9 cm) on Day 5. The greatest reduction in PPTs was observed over the masseter muscle. Females experienced higher pain, greater functional impairment, and greater sensitivity to mechanical stimuli than males. Conclusion: Intramuscular injection of NGF is a useful model with which to explore the mechanisms, and sex differences, present in clinical TMD.

Physiological responses and perceived comfort to high-flow nasal cannula therapy in awake adults: effects of flow magnitude and temperature.

Clinical use of heated, high-flow nasal cannula (HFNC) for noninvasive respiratory support is increasing and may have a therapeutic role in stabilizing the upper airway in obstructive sleep apnea (OSA). However, physiological mechanisms by which HFNC therapy may improve upper airway function and effects of different temperature modes are unclear. Accordingly, this study aimed to determine effects of incremental flows and temperature modes (heated and nonheated) of HFNC on upper airway muscle activity (genioglossus), pharyngeal airway pressure, breathing parameters, and perceived comfort. Six participants (2 females, aged 35 ± 14 yr) were studied during wakefulness in the supine position and received HFNC at variable flows (0-60 L/min) during heated (37°C) and nonheated (21°C) modes. Breathing parameters via calibrated Respitrace inductance bands (chest and abdomen), upper airway pressures via airway transducers, and genioglossus muscle activity via intramuscular bipolar fine wire electrodes were measured. Comfort levels during HFNC were quantified using a visual analog scale. Increasing HFNC flows did not increase genioglossus muscle activation despite increased negative epiglottic pressure swings (P = 0.009). HFNC provided ∼7 cmH2O positive airway pressure at 60 L/min in nonheated and heated modes. In addition, increasing the magnitude of HFNC flow reduced breathing frequency (P = 0.045), increased expiratory time (P = 0.040), increased peak inspiratory flow (P = 0.002), and increased discomfort (P = 0.004). Greater discomfort occurred at higher flows in the nonheated versus the heated mode (P = 0.034). These findings provide novel insight into key physiological changes that occur with HFNC for respiratory support and indicate that the primary mechanism for improved upper airway stability is positive airway pressure, not increased pharyngeal muscle activity.NEW & NOTEWORTHY This study evaluated upper airway muscle function, breathing, and comfort across different HFNC flows and temperatures. There were no increases in genioglossus muscle activity at higher flows despite greater negative epiglottic pressure swings. Increasing negative pressure swings was associated with increasing discomfort in the nonheated mode. HFNC was associated with ∼7 cmH2O increase in positive airway pressure, which may be the primary mechanism for upper airway stability with HFNC rather than increases in pharyngeal muscle activity.

Age trends and sex differences of alpha rhythms including split alpha peaks.

OBJECTIVE: To investigate age trends, sex differences, and splitting of alpha peaks of the EEG spectrum in the healthy population. METHODS: An automated multi-site algorithm was used to parametrize the alpha rhythm in 1498 healthy subjects aged 6-86 years. Alpha peaks identified from multiple electrode sites were organized into clusters of similar frequencies whose sex differences and age trends were investigated. RESULTS: Significant age-related trends were observed for frequency, position, and amplitude of dominant alpha peaks. Occipital sites had alpha clusters of higher average frequency, higher power, and greater presence across the scalp. Frequency and power differences were found between the sexes. CONCLUSION: Observed increases in alpha frequency in children and decreases in the elderly were consistent with those from earlier studies. A large fraction of participants (≈ 44%) showed multiple distinct alpha rhythm thus investigations which only examine the alpha frequency with the highest peak power can produce misleading results. The strong dependence of alpha frequency on age and anterior-posterior position indicates use of a fixed alpha frequency band is insufficient to capture the full characteristics of the alpha rhythm. SIGNIFICANCE: This study establishes alpha rhythm parameter ranges (including power and frequency) in the healthy population, and quantifies the variation in alpha frequency across the scalp. The automated characterization enables objective evaluations of alpha band activities over large samples. These findings are potentially useful in testing theories of alpha generation, where splitting of the alpha rhythm has been theoretically predicted to occur in individuals with large differences in axon length between anterior and posterior corticothalamic loops.

Neurophysiological changes with age probed by inverse modeling of EEG spectra.

OBJECTIVE: To investigate age-associated changes in physiologically-based EEG spectral parameters in the healthy population. METHODS: Eyes-closed EEG spectra of 1498 healthy subjects aged 6-86 years were fitted to a mean-field model of thalamocortical dynamics in a cross-sectional study. Parameters were synaptodendritic rates, cortical wave decay rates, connection strengths (gains), axonal delays for thalamocortical loops, and power normalizations. Age trends were approximated using smooth asymptotically linear functions with a single turning point. We also considered sex differences and relationships between model parameters and traditional quantitative EEG measures. RESULTS: The cross-sectional data suggest that changes tend to be most rapid in childhood, generally leveling off at age 15-20 years. Most gains decrease in magnitude with age, as does power normalization. Axonal and dendritic delays decrease in childhood and then increase. Axonal delays and gains show small but significant sex differences. CONCLUSIONS: Mean-field brain modeling allows interpretation of age-associated EEG trends in terms of physiological processes, including the growth and regression of white matter, influencing axonal delays, and the establishment and pruning of synaptic connections, influencing gains. SIGNIFICANCE: This study demonstrates the feasibility of inverse modeling of EEG spectra as a noninvasive method for investigating large-scale corticothalamic dynamics, and provides a basis for future comparisons.

Automated characterization of multiple alpha peaks in multi-site electroencephalograms.

The identification of alpha rhythm in the human electroencephalogram (EEG) is generally a laborious task involving visual inspection of the spectrum. Moreover the occurrence of multiple alpha rhythms is often overlooked. This paper seeks to automate the process of identifying alpha peaks and quantifying their frequency, amplitude and width as a function of position on the scalp. Experimental EEG was fitted with parameterized spectra spanning the alpha range, with results categorized by multi-site criteria into three distinct classes: no distinguishable alpha peak, a single alpha peak, and two alpha peaks. The technique avoids visual bias, integrates spatial information, and is automated. We show that multiple alpha peaks are a common feature of many spectra.

Wave-number spectrum of electroencephalographic signals.

A recently developed, physiologically based continuum model of corticothalamic electrodynamics is used to derive the theoretical form of the electroencephalographic wave-number spectrum and its projection onto a one-dimensional recording array. The projected spectrum is found to consist of a plateau followed by regions of power-law decrease with various exponents, which are dependent on both model parameters and temporal frequency. The theoretical spectrum is compared with experimental results obtained in other studies, showing good agreement. The model provides a framework for understanding the nature of the spatial power spectrum by linking the underlying physiology with the large-scale dynamics of the brain.