Mechanisms of peripheral and central sensitization. (a) In the normal status, signals induced by noxious stimuli and non-noxious (e.g. tactile) stimuli are transduced via the pathway of nociceptive and tactile processing, respectively. (b) In peripheral sensitization, neurons would show increased responsiveness to noxious stimuli. For example, the inflammation at the peripheral site (i.e. the light red area) may reduce the threshold to evoke a response. The signals for subsequent nociceptive processing are amplified. Therefore, peripheral sensitization may be associated with hyperalgesia. (c) In secondary hyperalgesia (in contrast to primary hyperalgesia (b)), noxious stimulation to the area surrounding the site of injury or inflammation (i.e. the black arrow) elicits an amplified pain. The amplification is mediated by the central neurons (i.e. the red circle), which have been sensitized by constantly receiving nociceptive inputs from the primary lesion (i.e. the circled light grey area). (d) In allodynia, non-noxious tactile stimuli are conveyed by the Aβ fibre elicit pain. Note that at the central level, both the nociceptive and tactile pathways converge on central nociceptive neurons. The central neurons (the red square) have been sensitized by constantly receiving nociceptive inputs from the primary lesion.
6.4
Brain features associated with chronic orofacial pain. (a) Brain activation associated with chronic orofacial pain. Meta-analytical findings reveal a consistent pattern of higher brain activation in the left medial and posterior thalamus and lower brain activation in the left posterior insula in patients with chronic orofacial pain (COFP) compared to healthy controls. Source: Ayoub et al. (2018). Reproduced with permission of Elsevier. (b) Functional connectivity of patients with temporomandibular disorder (TMD)-related pain. The left panel reveals that TMD patients showed enhanced functional connectivity (FC) between the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC)/precuneus (PCu)/retrosplenial cortex (RSC) compared to healthy controls. The right panel reveals that functional connectivity between the mPFC and medial thalamus/PAG was positively correlated with pain rumination in TMD patients. Source (insets): Kucyi et al. (2014), p.3969–3975 with permission of the Society for Neuroscience under the terms of the Creative Commons Attribution 4.0 International License.
7.1
Conceptual links between oral health and cognitive functions. (a) The framework of the brain–stomatognathic axis (BSA). The framework highlights that the brain plays a key role in behavioural adaptation in feeding and oral care behaviour, which further relates to oral health. (b) The potential role of the brain in behavioural adaptation. Poor oral health may be attributed to increasing difficulty in conducting health-related behaviour (e.g. being unable to brush teeth), which is derived from neurodegenerative disorders. (c) The potential role of oral factors in brain pathologies. The ‘oral-on-brain effect’ may be associated with multiple factors, such as reduced sensory feedback from the loss of occlusal contact or increased periodontal inflammation/infection. Notably, when the brain is affected by poor oral health, it may be followed by worse adaptation of feeding and oral care behaviour, which furthers exacerbates one’s oral health. (d) The potential role of a common factor that affects both cognitive and oral functions. For example, aging is associated with structural and functional alterations of the cerebellum, which relates to not only oral sensorimotor functions but also cognition. The arrow filled with a slash pattern denotes the potential causal links of the framework.
8.1
The concept of neuroplasticity and functional adaptation. (a) With a ‘preprogrammed’ nervous system, our behaviours responding to environmental stimuli are determined by a fixed set of stimulus–response links. For example, a great danger will elicit a stronger emotional response compared to a mild danger (the upper panel). However, our nervous system is modifiable and can be tuned according to environmental changes. Long-term experience may sculpt the brain at the structural and functional levels, leading to different behaviours responding to environmental stimuli. For example, past experience may predispose the brain to be more sensitive to danger and make a stronger emotional response (the lower panel). (b) Functional adaptation is associated with the improvement of one’s functional performance under environmental challenges. For example, individuals learn to run faster (i.e. increased performance) when they are threatened by a greater danger (the upper panel). Compensation, in contrast, highlights the restoration of performance from a worse status back to a normal status. For example, individuals with a disability can run as quickly as normal individuals when facing danger by compensating their mobility with the help from tools and rehabilitative therapy (the lower panel).
8.2
Experimental design of neuroimaging research on brain plasticity. (a) A cross-sectional study reveals a significant difference in structural brain features between subjects with and without a professional skill (e.g. driving). Individual variations in brain features further relate to the duration of skill training (the left panel). Results from the cross-sectional design only suggest, but not confirm, the causal direction of a plastic effect. The difference in brain features (as observed by neuroimaging) may be attributed to prior experience of training (the middle panel). However, it is also possible that the individual differences in the brain features predispose their performance of a skill (the right panel). (b) To better elucidate the plastic effect of training, a longitudinal design is used to assess the performance and brain features at different stages of training. Importantly, one can assess whether the plastic effect, i.e. changes in brain features during the training session, can last for a period or vanish right after the termination of training. (c) The same longitudinal design also helps to elucidate individual differences in their performance. For example, the variation in brain features may account for the difference in learning speed.
9.1
Major aims of brain–stomatognathic integrative assessment (BSIA). (a) Prediction of long-term changes in oral functions. Individual differences in brain reserve and cognitive reserve may play a key role in their susceptibility to diseases. The BSIA, which includes the assessment of cognitive functions of older people, would help to predict the future condition of individual oral health. (b) Classification of patients with different risks of oral diseases. The BSIA helps to classify the patients for their risk of oral diseases and the prognosis of treatment, based on a full-scale assessment of general physical and mental status.
9.2
Key elements for implementing the brain–stomatognathic integrative assessment. (a) The multidisciplinary investigation can be undertaken in a hospital, where different departments are in charge of different assessments. Critically, the results of an assessment from one discipline (e.g. the score of cognitive tests from neurologists) are distributed for the use of other disciplines (e.g. dentistry). For example, the cognitive performance of older patients, as assessed by neurologists, is available for prosthodontists to evaluate if patients can adapt well to their new dentures. (b) In contrast to the hospital setting, a home-based assessment can be facilitated by the use of teledentistry approaches and digital technology. For example, in long-term care institutes or at home, patients can record their own oral status by photographing (via a smartphone). The image record may include a photo about their intraoral conditions (e.g. bleeding gum) or performance of oral functions (e.g. the food bolus after chewing). The images are sent to the cloud storage service for further analysis. A preliminary assessment is performed automatically by machine-learning-based algorithms, and critical problems (e.g. a poor oral mixing ability) are screened and forwarded to dental professionals for further evaluation.
9.3
An example of neuroimaging investigation combined with animal research. Using structural MRI, Avivi-Arber et al. (2017) compared the post-mortem brain volume between the mice that received molar extraction and those who received sham operation. Tooth extraction was associated with a widespread reduction in volumes of brain regions of sensorimotor and cognitive–affective processing. Source:
