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The study investigates Temporomandibular Joint Disorder (TMJD) through an interdisciplinary approach, focusing on its complex pathophysiology and neural mechanisms, emphasizing the role of pain perception and modulation. It highlights the importance of personalized treatment strategies due to the disorder's complexity, while recognizing advances in neuroscience that offer new therapeutic avenues such as neuromodulation and biofeedback. The study advocates for further research integrating neuroscience, dentistry, and psychology to improve patient care and quality of life for those affected by TMJD.

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0% found this document useful (0 votes)
5 views8 pages

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The study investigates Temporomandibular Joint Disorder (TMJD) through an interdisciplinary approach, focusing on its complex pathophysiology and neural mechanisms, emphasizing the role of pain perception and modulation. It highlights the importance of personalized treatment strategies due to the disorder's complexity, while recognizing advances in neuroscience that offer new therapeutic avenues such as neuromodulation and biofeedback. The study advocates for further research integrating neuroscience, dentistry, and psychology to improve patient care and quality of life for those affected by TMJD.

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Archives of Oral Biology 164 (2024) 106001

Contents lists available at ScienceDirect

Archives of Oral Biology


journal homepage: www.elsevier.com/locate/archoralbio

Temporomandibular Joint Disorder: An integrated study of the


pathophysiology, neural mechanisms, and therapeutic strategies
Guofang Lu a, Rui Du b, 1, *
a
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of
Digestive Diseases, Fourth Military Medical University, Xi’an 710032, China
b
Institute for Biomedical Sciences of Pain, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China

A R T I C L E I N F O A B S T R A C T

Keywords: Objective: The study aims to investigate Temporomandibular Joint Disorder (TMJD) through a interdisciplinary
Temporomandibular Joint Disorder (TMJD) lens, integrating insights from neuroscience, dentistry, and psychology to dissect its complex pathophysiology
Neurobiological mechanisms and neural mechanisms. It focuses on exploring the neurobiological underpinnings of TMJD, emphasizing the
Pain perception and modulation
role of pain perception, modulation, and the impact of neurophysiological changes on the disorder.
Neuromodulation and biofeedback
Interdisciplinary approach
Design: This is a comprehensive narrative review of the literature.
Results: Research findings pinpoint altered pain perception and modulation processes as central neural mecha­
nisms contributing to TMJD, highlighting the importance of personalized treatment approaches due to the dis­
order’s complexity and patient variability. The study recognizes advances in neuroscience offering new
treatment avenues, such as neuromodulation and biofeedback, which provide non-invasive and personalized
options. However, it also addresses the challenges in TMJD research, such as the multifaceted nature of the
disorder and the need for more comprehensive, interdisciplinary strategies in research and clinical practice.
Conclusions: TMJD is a multifaceted disorder requiring an interdisciplinary approach for effective management.
The study stresses the crucial role of neuroscience in understanding and treating TMJD, facilitating the devel­
opment of innovative treatment strategies. It emphasizes the need for further research, advocating an integrated
approach that combines neuroscience, dentistry, and psychology to address TMJD’s complexities comprehen­
sively and improve patient care, thereby enhancing the quality of life for affected individuals.

1. Introduction influencing the overall quality of life of the affected individuals.


Therefore, the diagnosis and treatment of TMJD are paramount for pa­
The Temporomandibular Joint Disorder (TMJD) refers collectively to tient care in clinical practice. A precise diagnosis of TMJD necessitates a
a complex array of conditions that affect the temporomandibular joint detailed medical history, a comprehensive clinical examination, and
(TMJ) and its surrounding muscles, skeletal structures, and soft tissues. auxiliary investigations such as imaging analyses. The treatment mo­
This disorder extends beyond oral health and is intertwined intricately dalities available for TMJD are diverse, ranging from pharmacotherapy,
with the overall well-being of an individual, as it induces a multitude of physical therapy, and behavioral interventions to surgical interventions,
symptoms such as headaches, facial pain, tinnitus, and neck pain. TMJD which are aimed at alleviating pain, ameliorating the functional im­
is characterized by manifestations of joint pain, functional impairments, pairments, and restoring the normal functioning of the jaw joint and the
and noises during jaw movement, which frequently originate from masticatory muscles to the extent possible (De Rossi et al., 2014).
discordant function between the jaw joint and masticatory muscles, However, the implications of TMJD extend beyond the local pain and
abnormal positioning of the articular disc, and joint inflammation or the functional impairments, as this condition could potentially induce or
degeneration (Scrivani et al., 2008). These symptoms, in addition to exacerbate psychological health issues such as anxiety and depression,
affecting the oral cavity, impact fundamental functions such as chewing, thereby further impacting the overall quality of life of the affected in­
speaking, swallowing, and facial expressions, thereby significantly dividuals (Liou et al., 2023). Frequent medical consultations, diagnostic

* Corresponding author.
E-mail address: [email protected] (R. Du).
1
ORCID: 0000-0001-7427-6622.

https://doi.org/10.1016/j.archoralbio.2024.106001
Received 8 February 2024; Received in revised form 5 May 2024; Accepted 8 May 2024
Available online 13 May 2024
0003-9969/© 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
G. Lu and R. Du Archives of Oral Biology 164 (2024) 106001

tests, and treatments place an additional burden on patients, causing activation, thereby sensitizing these neurons to respond to stimuli that
stress, while also leading to significant consumption of medical re­ ordinarily wouldn’t elicit pain sensations (Linley et al., 2008).
sources. Therefore, effective management of TMJD is of great signifi­ Furthermore, these inflammatory mediators facilitate the expression
cance from both social and economic perspectives and would contribute and modification of ion channel functions, such as those of sodium and
positively to enhancing the quality of life of patients and optimizing the potassium channels, thereby amplifying the excitability of nerve end­
utilization of available medical resources (Gauer & Semidey, 2015). ings. An example of this is the elevation of nerve growth factor (NGF),
Neuroscience plays an indispensable role in understanding and which stimulates the expression of particular sodium channel subtypes
treating TMJD by offering a pivotal perspective in unraveling the com­ within pain-conducting fibers, thereby bolstering their ability to relay
plex pathological mechanisms of TMJD and formulating effective ther­ pain sensations (Mamet et al., 2003). Another crucial aspect of periph­
apeutic strategies accordingly. Advances in neuroscience research have eral sensitization is its interaction with central sensitization. The sus­
deepened the comprehension of the neurobiological mechanisms un­ tained and enhanced pain signal input, resulting from this interaction,
derlying TMJD by elaborating on every aspect of this condition, ranging can promote neuroplastic changes at the level of the spinal cord’s dorsal
from pain perception and conduction to modulation (Tashiro & Bereiter, horn, a process known as central sensitization. This further amplifies
2020). TMJD patients exhibit enhanced pain perception, altered con­ pain perception, creating a complex pain amplification circuit that ex­
duction mechanisms, and dysregulation, which underscore the central acerbates the impact of TMJD on patients (Woolf, 2011). Pain conduc­
role of the nervous system in TMJD and highlight the importance of tion is the process of nociceptive signals traveling from the receptors via
intensive research into the neurobiological mechanisms underlying this the neural fibers to the central nervous system (Janevic et al., 2022).
condition. The emergence of novel therapeutic approaches in the field of Pain modulation involves the brain and the central nervous system
neuroscience, such as neuromodulation and biofeedback, have sub­ mitigating the sensation of pain through the release of inhibitory neu­
stantially improved the potential of treating TMJD through a precise rotransmitters, which have implications for multiple brain regions
regulation of neural activities (Criado et al., 2016; Festa et al., 2021). (Marks et al., 2009). In patients with TMJD, these pain-related mecha­
Such advanced technologies offer non-invasive, personalized treatment nisms are significantly altered or abnormal, which leads to heightened
options for achieving significant enhancement in the therapeutic out­ pain perception. A lowered pain threshold has been reported in patients
comes and the quality of life of patients with TMJD. However, several with TMJD, leading to greater sensitivity to pain among these patients
aspects of the neural mechanisms underlying TMJD remain elusive, and (Kothari et al., 2015). This might occur due to alterations in the noci­
the existing research is constrained by limitations and challenges that ceptive conduction pathways, anomalies in the central nervous system’s
demand innovative solutions and novel directions. Future research has processing of pain signals, or dysfunctions in the pain regulatory
to leverage the knowledge and techniques of neuroscience to better mechanisms (List & Jensen, 2017).
understand TMJD, from the aspects of functional alterations in the pain The pathomechanisms underlying TMJD are complex, with inflam­
networks to the potential of stem cell therapies, and accordingly develop mation playing a pivotal role. Inflammation not only directly contrib­
effective treatments for TMJD. Therefore, focusing on neuroscience is utes to pain and functional impairment in TMJD but also serves as a
crucial for unveiling the neurobiological foundations of TMJD and also critical mediator in the damage and repair processes of connective tis­
for propelling the research and treatment of TMJD in a new direction. sues. The onset of inflammation is typically triggered by several factors,
including mechanical stress, trauma, functional disturbances, and sys­
2. Neurobiological basis of TMJD temic diseases. Mechanical stress is among the most common causes.
Poor occlusal habits, such as bruxism (grinding of teeth) and clenching,
The incorporation of neurophysiological techniques in the research jaw tension, or inappropriate dental contacts, can lead to overuse of the
on TMJD has provided a pivotal perspective for comprehending the joint and surrounding muscles (Acharya et al., 2018). This overuse in­
neural mechanisms underlying this complex disorder, revealing intricate creases the intra-articular pressure, leading to displacement or wear of
dynamics in the multifaceted interplay of pain perception, conduction, the articular disc (a soft cushion located within the joint), thereby
and modulation. TMJD affects the sophisticated structure of TMJ and triggering a local inflammatory response. The inflammatory response
the surrounding muscular tissues, and its pathogenesis involves a exacerbates pain and functional impairment by promoting nociceptive
diverse array of biological, environmental, social, emotional, and sensitization and the activation of local immune cells. Trauma, such as
cognitive factors, leading to the manifestation of symptoms such as joint direct impacts to the chin or head, can inflict damage on the structures of
pain, limited functionality, and chewing difficulties (Gauer & Semidey, the TMJ, encompassing soft tissue injuries and fractures (Akkemik et al.,
2015). In a normal physiological state, pain perception involves the 2022). The inflammatory response induced by these injuries, intended to
recognition of noxious stimuli by the nociceptors, followed by the initiate the healing process, can concurrently lead to pain and swelling,
transmission of these recognitions as signals within the nervous system and potentially long-term joint dysfunction. Functional anomalies, like
and the eventual perception of the signals in the brain (McCarberg & the displacement or dislocation of the articular disc and joint instability,
Peppin, 2019). Peripheral sensitization represents a fundamental elevate friction and stress within the joint, thereby exacerbating
concept within pain research, denoting the heightened sensitivity of the inflammation (Kellenberger et al., 2019). The misalignment of the
peripheral nervous system in response to tissue injury or inflammation. articular disc holds particular importance as it not only precipitates
This heightened sensitivity leads to a reduction in the pain threshold and immediate joint pain but also potentially accelerates joint degeneration.
the ability of non-painful stimuli, like gentle touch, to elicit pain sen­ Systemic conditions, including rheumatoid arthritis and systemic lupus
sations. This mechanism has been documented in a range of pain con­ erythematosus, may impact the TMJ via inflammation mediated by the
ditions, with particular prominence in contexts of inflammatory and immune system (Shoohanizad et al., 2019). In such cases, the inflam­
neuropathic pain (Woolf, 2018). The process is chiefly driven by mod­ mation extends beyond the TMJ, manifesting as a component of the
ifications in pain-conducting fibers, especially C fibers and Aδ fibers, broader systemic disease pathology. At the cellular and molecular level,
which are pivotal in relaying pain signals to the central nervous system. inflammation enhances pain perception by liberating inflammatory
The phenomenon is rooted in a variety of biochemical processes. mediators, including cytokines, prostaglandins, and interleukins,
Initially, tissue injury or inflammation triggers cellular damage and alongside activating pain-sensitive receptors. These biochemical pro­
necrosis, culminating in the release of numerous inflammatory media­ cesses intensify the inflammation within the TMJ, creating a pernicious
tors, including prostaglandins, interleukins, tumor necrosis factor alpha, cycle that amplifies pain and disrupts function.
and nerve growth factor. These substances target peripheral nerve ter­ A profound understanding of these neurophysiological mechanisms
minals, notably nociceptors, inducing alterations in membrane poten­ could improve the diagnostic approaches and treatment strategies for
tial. Such alterations result in a lowered threshold for neuronal TMJD. However, the complexity of TMJD and the variability of the

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G. Lu and R. Du Archives of Oral Biology 164 (2024) 106001

condition among patients necessitate the use of personalized treatment processes. In addition, elastin-derived peptides (EDPs) play a significant
strategies, particularly to identify the specific pain mechanisms involved role in the pathology of TMJD. The activated elastin-binding protein
and accordingly develop targeted therapeutic approaches (Silva & Gal­ (EBP) signaling pathway induces inflammatory responses, leading to
dino, 2017). Recent years have witnessed an increase in the research chronic inflammation in the TMJ (Kobayashi et al., 2017). The roles of
exploring the neurophysiology of TMJD, particularly aimed at under­ glutamate receptors and transient receptor potential (TRP) channels are
standing the mechanisms of central sensitization in pain (Ferrillo et al., also paramount, particularly in the genesis and persistence of pain in the
2022). Study has demonstrated differences in the temporal summation craniofacial muscle. These receptors and channels interact during the
of second pain and the subsequent sensations between the patients with sensitization process of trigeminal nociceptors, collaboratively regu­
TMJD and those without joint pain, emphasizing that the central lating pain perception in the muscles of the TMJ (Chung & Ro, 2020).
sensitization mechanisms could vary due to joint and muscular pain Another aspect that should not be ignored is the association between
(Santiago et al., 2022). The recent technological advancements have led joint effusion and TMJ pain. An increase in intra-articular pressure or
to the emergence of biomaterial-assisted drug delivery, which is being mechanical trauma could activate or sensitize the nociceptive neurons
considered for the treatment of patients with TMJD involving inflam­ within the joint. One study has reported a significant statistical corre­
mation and abnormal neural modulation to prevent cartilage degrada­ lation between the presence of joint effusion and self-reported TMJ pain
tion and protect the bone underneath the TMJ (Dashnyam et al., 2018). (Crow et al., 2017). In summary, the specific mechanisms underlying the
Moreover, the molecular and cellular mechanisms underlying the pain pain signals in TMJD reportedly comprise the amplification of noci­
symptom in TMJD, such as the roles of inflammatory mediators, neu­ ceptive signals in the trigeminal nerve system and the influences of
rotrophic factors, and intercellular signaling, are being explored. The various hormones, inflammatory responses, alterations in the neural
findings from such studies would lead to a deeper understanding of the conduction pathways, and changes in joint fluid dynamics.
neurophysiological mechanisms of TMJD while providing robust evi­ Advanced research on the processing of TMJD-related pain signals in
dence to support the clinical diagnosis and treatment of this condition, the brain has revealed that this processing is quite complex and involves
indicating potential directions for future investigations in this area of multiple brain regions, each of which plays a distinct role in the process.
research. Research has indicated changes in spontaneous brain activity in the
anterior insula (AI) and its functional connectivity with the left mid-
3. Association between TMJD and the central nervous system cingulate cortex (MCC) in individuals with temporomandibular joint
disorder (TMJD). These findings suggest that the AI and MCC may play a
3.1. Pain in TMJD and the underlying mechanisms significant role in the perception and processing of pain associated with
TMJD (Zhang et al., 2018). In addition, TMJD pain could be closely
The pain signal mechanisms in TMJD are diverse and complex, associated with the thalamus, primary sensory cortex, insula, anterior
although the amplification of nociceptive signals in the trigeminal nerve cingulate cortex, and MCC, which are critical regions in the processing
system is considered to play a key role. A chronic pain state in TMJD of pain signals, regulation of emotional responses, and integration of
could be maintained through adaptive changes, both peripherally and sensory input (Suenaga et al., 2016). The increased activity in the cen­
centrally, which lead to significant amplification of the pain signals in tral amygdala and ventrolateral periaqueductal gray during persistent
the trigeminal nerve system (Chichorro et al., 2017). Moreover, it is pain in TMJD highlights the role of these regions in persistent pain
important to consider the influence of estrogen on TMJD pain. Fluctu­ perception and emotional responses in this condition (Nascimento et al.,
ations in hormone levels are recognized for their crucial influence on the 2021). Research on the choroid plexus in the brain has revealed the role
development and progression of TMJD. Key hormones, including es­ of this region in TMJD pain processing, particularly in relation to the
trogen, cortisol, thyroid hormones, and growth hormone, are instru­ neuroinflammatory activity in the central nervous system, which could
mental in managing aspects such as inflammation, pain perception, lead to increased permeability of the blood-brain barrier, thereby
tissue regeneration, and bone metabolism. These functions collectively affecting the processing of pain signals in this condition (Barkhordarian
contribute to their indirect or direct impact on TMJD’s trajectory. Es­ et al., 2018). Interestingly, a study reported changes in the functional
trogen, notably, modulates TMJD symptoms by its role in controlling connectivity between the hypothalamus and the anterior cingulate
inflammatory mechanisms, modifying pain sensitivity, and affecting the cortex in the brain of a patient with TMJD, thereby providing a novel
behaviors of chondrocytes and osteocytes within the TMJ. For instance, perspective indicating a complex link between chronic pain mainte­
elevated levels of estrogen may promote inflammation and increase pain nance and emotional regulation (Smith et al., 2022). These research
sensitivity, while fluctuations in estrogen levels are associated with the findings, in addition to enhancing the understanding of the mechanisms
exacerbation of TMJD symptoms (Hogrefe et al., 2022). This sheds light underlying pain signal processing in the brain of patients with TMJD,
on why the incidence of TMJD is higher in women, particularly during offer novel insights for pain management and treatment in these
their reproductive years, compared to men. Cortisol, known as the stress patients.
hormone, can rise abnormally under conditions of prolonged stress or
chronic fatigue, impacting the function of the immune system and 3.2. TMJD and neurophysiological activity
heightening the body’s sensitivity to inflammation. In the context of
TMJD, persistent stress and elevated cortisol levels can exacerbate pain When investigating the mechanisms underlying the processing of
and inflammation, worsening the condition (Raison & Miller, 2003; TMJD-related pain signals in the brain, the key neurophysiological ac­
Somvanshi et al., 2020). Thyroid hormones, involved in regulating the tivities involved could reveal the complexity and multidimensionality of
metabolism of bones and soft tissues, can also impact the health of the pain signal processing. The role of the prefrontal cortex (PFC) in this
TMJ. Abnormalities in thyroid function may affect TMJD by altering the pain processing is the most significant. In addition to being crucial for
elasticity of soft tissues and the remodeling processes of bone tissue, executive functions, PFC plays a role in pain processing, particularly
indirectly influencing the development of TMJD (Grenga et al., 2004). through its connections with the other regions of the brain. Changes in
Growth hormone is essential for the health of both cartilage and bone, the levels of neurotransmitters, gene expression, glial cells, and neuro­
and changes in its levels can significantly impact the structural and inflammation in these other brain regions could lead to alterations in the
functional integrity of the TMJ. Such changes may influence the severity structure, activity, and connectivity of the PFC (Ong et al., 2018).
of TMJD and the patient’s ability to recover (Ok et al., 2020). In Further research into the anterior cingulate cortex (ACC) identified a
conclusion, the effects of hormonal fluctuations on TMJD are compre­ novel form of synaptic, time-dependent long-term depression (tLTD) and
hensive, affecting a range of factors from the regulation of inflammation indicated that impairment in tLTD could persist even after the me­
and pain sensitivity to tissue healing capabilities and bone metabolism chanical sensitivity has been restored. Therefore, it is implied that

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G. Lu and R. Du Archives of Oral Biology 164 (2024) 106001

transient neuralgia might leave a permanent mark in specific incoming quality also plays a crucial role, possibly affecting TMJD by influencing
pathways of the brain, manifesting as a synaptic plasticity disorder the hormone levels and altering the activities related to emotion and
(Hogrefe et al., 2022). In addition, conditioned pain modulation (CPM), pain processing regions in the brain, including changes in the cortisol
a potent endogenous analgesic mechanism, is influenced by the brain­ and melatonin levels and alterations in the sleep-regulating neural
stem circuits as well as by cortical regions such as the anterior, pathways, thereby further contributing to the complexity of TMJD (Gaş
mid-cingulate, and dorsolateral prefrontal cortex, which may exhibit et al., 2021). However, these factors do not exist in isolation and exhibit
reduced responses during CPM analgesia, thereby causing further CPM significant interactions and synergistic influences. For instance, stress
(Youssef et al., 2016). Lastly, the studies on brain circuits in nociception and emotional issues could cause a decline in sleep quality, and poor
and emotional processing have emphasized the existence of central sleep could then exacerbate the stress and emotional issues, forming a
nervous system changes during emotional and motivational pain signal vicious cycle that collectively promotes the development of TMJD.
processing in chronic pain. These changes could be related to the Staniszewski et al. indicated that HPA axis activity could be upregulated
interaction between nociception and emotion and are, therefore, crucial in patients with TMJD, and this could be related to the interactions of
for understanding these mechanisms and their mutual influences in the above-stated factors (Staniszewski et al., 2018). Numerous studies
chronic pain (Becker et al., 2018). In summary, these findings regarding have corroborated this multidimensional interplay and influence of
neurophysiological activity demonstrate that the processing of different pathways, ranging from biochemical analyses to neuroimaging
TMJD-related pain signals in the brain is complex and involves various research, all of which have offered profound insights into how these
biological processes, including changes in the levels of neurotransmit­ factors affect TMJD by impacting the nervous system and the endocrine
ters and receptors and modulation of neuronal activity, in addition to system. In summary, stress, emotion, and sleep significantly affect TMJD
the involvement of different brain regions with emotional and cognitive through both individual neurobiological mechanisms and mutual
functions. interaction mechanisms. These complex mechanisms include changes in
the neurotransmitter balance, fluctuations in the levels of hormones,
and changes in the activity of specific brain regions.
3.3. TMJD, stress, emotion, and sleep

4. Neuroscience-based treatment strategies for TMJD


Stress, emotion, and sleep are important phenomena to be investi­
gated when exploring the complexities of TMJD, and each of the three
4.1. Current treatment approaches for TMJD: pharmacological
exerts its impact through its unique and specific neurobiological path­
intervention, interdisciplinary therapy, and cognitive behavioral therapy
ways (Fig. 1). The impact of stress is significant, as it activates the
hypothalamus-pituitary-adrenal (HPA) axis, which then releases hor­
In the field of TMJD treatment, pharmacological intervention,
mones such as cortisol that induce changes in the nervous system. This
interdisciplinary therapy, and cognitive-behavioral therapy (CBT) offer
ultimately affects muscle tension and pain perception, establishing a
unique advantages, and together, they form a multifaceted treatment
network involving the chewing system, the TMJ, and the orofacial or­
paradigm. Pharmacological intervention primarily focuses on allevi­
gans in interaction with the "stress neural matrix," "pain neural matrix,"
ating pain and inflammation and improving joint function using non-
"limbic system," and "neuroimmune-endocrine system". Such in­
steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, antide­
teractions cause changes in neural connectivity, leading to the diversi­
pressants, and anticonvulsants to directly target the symptoms (Oua­
fied symptoms of TMJD (Dutra Dias et al., 2021). On the emotional
nounou et al., 2017). This approach offers the advantages of immediate
dimension, the states of anxiety and depression disbalance the levels of
relief effects, although the long-term application of this method could
neurotransmitters such as serotonin and catecholamines and alter the
cause side effects such as indigestion, drowsiness, or dependence, while
neurophysiological activities in the brain, thereby increasing muscle
the therapeutic efficacy of certain drugs used in this approach might be
tension and pain perception, potentially leading to functional disorders
limited (Andre et al., 2021; Ouanounou et al., 2017). The selection and
and increased pain in the TMJ (Zuszek et al., 2019). A decline in sleep

Fig. 1. Stress, emotion, and sleep may affect each other mutually in TMJD. Pattern graph of Stress, emotion, and sleep affect TMJD through both individual
neurobiological mechanisms and mutual interaction mechanisms.

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G. Lu and R. Du Archives of Oral Biology 164 (2024) 106001

dosage adjustment of pharmacological treatments should be based on (Wieckiewicz et al., 2015; Breton-Torres et al., 2016; Silant’Eva, 2010).
the specific symptoms of the patient, the medical history, and the drug CBT, on the other hand, undertakes a psychological perspective and
response if optimal therapeutic outcomes have to be achieved. More­ aims to reduce pain and improve the quality of life of patients by
over, the study suggests that for prolonged therapeutic outcomes, changing their thought patterns and behaviors. This treatment approach
pharmacological treatment should be combined with physical therapy comprises the elements of education, relaxation training, coping strat­
or cognitive-behavioral therapy (CBT) (Gauer & Semidey, 2015). egy training, and emotional regulation skills, and might be particularly
Interdisciplinary therapy including physical therapy, acupuncture and suitable when emotional and behavioral factors play significant roles in
rehabilitation medicine. Physical therapy involves methods such as the pain perception of patients. While CBT is considered effective, it
thermotherapy, cryotherapy, ultrasound treatment, and manual therapy relies on guidance from professional mental health experts and requires
to reduce pain, increase the range of joint motion, and improve muscle active participation from the patient. The content and duration of CBT
function. This treatment approach is applied widely as it is safe and might have to be adjusted based on specific patient requirements and
efficient, although long-term adherence by patients is necessary, and treatment responses, and certain patients could require additional sup­
responses could vary among individuals. Physical therapy plans have to port and extra therapy sessions. According to the literature, CBT
be customized for each patient based on the specific symptoms and significantly reduces pain and improves the quality of life of patients
treatment responses, and at certain times, a combination with other with TMJD, although it is suggested that for long-term therapeutic ef­
treatments is required to achieve optimal results. However, studies fects, CBT should be combined with either pharmacological treatment or
reporting the long-term effects of physical therapy are relatively scarce physical therapy (Matheson et al., 2023). In summary, TMJD treatment
(Dolwick & Freburg-Hoffmeister, 2019). Moreover, physical therapists requires a comprehensive approach integrating pharmacological treat­
also utilise the concepts of neuromuscular function and motor control of ment, physical therapy, and cognitive-behavioral therapy, tailored to
the muscles of mastication in their approach to assessing and managing specific patient requirements to achieve the best therapeutic outcomes
TMJD (National Academies of Sciences, E. A. M., Medicine, H. A., Di­ (Fig. 2).
vision, Services, B. O. H. C., Policy, B. O. H. S., to, C. O. T. D., &
Treatment, C, 2020). Acupuncture is an effective and enduring treat­ 4.2. Neuromodulation and biofeedback: the emerging neuroscience-based
ment for TMJD, involving the insertion of needles at specific acupoints treatment strategies for TMJD
to alleviate pain and enhance joint functionality. It proves beneficial for
both acute and chronic patients without associated side effects(Sousa Neuromodulation and biofeedback are emerging strategies for TMJD
et al., 2014; Jung et al., 2011; Noiman et al., 2010). Concurrently, treatment that have demonstrated innovative breakthroughs in the
rehabilitation medicine employs a spectrum of non-invasive therapeutic application of neuroscience to the clinical field. Neuromodulation uti­
interventions to aid in the recovery of joint function and pain alleviation lizes precise electrical or magnetic stimulation to fine-tune the neural
in TMJD patients. These interventions include postural correction activity of specific brain regions. This approach, particularly the appli­
techniques, therapeutic exercises, and mobility enhancement regimens cation of transcranial direct current stimulation (tDCS), has

Fig. 2. Four treatments for TMJD. The specific treatments of Pharmacological intervention, Interdisciplinary therapy, Cognitive behavioral therapy and Elec­
tromyography biofeedback.

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G. Lu and R. Du Archives of Oral Biology 164 (2024) 106001

demonstrated great potential in chronic pain reduction and functional of TMJD, future research should focus on identifying the optimal
improvement in the treatment of TMJD (Silva & Galdino, 2017). treatment parameters, assessing the long-term treatment effects, and
Concurrently, biofeedback serves as a non-invasive treatment approach exploring the synergistic effects of different treatment methods when
that enables patients to become aware of and control their physiological used in combination with the traditional treatment approaches.
functions, such as muscle electrical activity. This approach has been Further, interdisciplinary collaboration among neuroscience,
particularly effective in reducing pain and tension in the masticatory dentistry, and psychology is crucial in TMJD research and treatment.
muscles through electromyography biofeedback (EMG-BF), with sig­ The integration of these fields would provide a comprehensive
nificant results achieved in terms of reducing muscular electrical activity perspective for understanding and addressing this complex disorder.
and alleviating pain (Criado et al., 2016). Neuroscience would delve into aspects such as pain perception,
The above-described three emerging treatment methods (Neuro­ emotional regulation, and neurotransmitters, contributing significantly
modulation, biofeedback and EMG-BF) for TMJD have been applied to the identification of the neurobiological basis of TMJD. Dentistry
clinically, with the studies on using biofeedback and coordinated exer­ would focus on the structure and function of the oral and maxillofacial
cises of the tongue and palatal arch as part of TMJD treatment reporting regions, thereby laying a foundation for direct intervention measures for
noticeable significant pain relief and functional changes in the pain- TMJD, such as dental orthopedics and oral maxillofacial surgery. Psy­
related networks within the brain (Festa et al., 2021). The advantages chology would consider and explore the crucial role of psychosocial
of neuromodulation and biofeedback in TMJD treatment include their factors in the development of TMJD, contributing significantly to the
non-invasive and generally low-risk characteristics and the ability to treatment of this condition by assessing and addressing the psycholog­
provide personalized treatment by adjusting the treatment parameters ical states and behavioral patterns of patients. However, challenges
based on specific patient requirements. However, certain challenges would nonetheless be encountered in this interdisciplinary collaboration
related to the requirement of specialized equipment and professional as well, such as communication and coordination between the different
personnel for the treatment remain, and the therapeutic effects of these disciplines, resource allocation, and the difficulty of implementing in­
approaches could also vary among individuals. Therefore, future tegrated treatment plans in clinical practice. The communication and
research on the treatment of TMJD using neuromodulation and collaboration between these fields could be promoted through several
biofeedback should focus on identifying the best treatment parameters, future initiatives, such as establishing interdisciplinary training and
assessing the long-term treatment effects, and exploring the synergistic education programs, encouraging research collaboration between the
effects of these treatments when used in combination with the tradi­ different disciplines, and forming interdisciplinary teams in clinical
tional treatment methods. In addition, broader clinical trials and practice. These measures would facilitate the future research and
multicenter studies would facilitate the evaluation of the applicability development of treatment strategies designed specifically for the holistic
and effectiveness of these and other emerging treatment methods in requirements of patients by leveraging the knowledge and techniques
different patient populations (Criado et al., 2016; Festa et al., 2021). from these fields to develop further effective and personalized treatment
plans for TMJD. Ultimately, this interdisciplinary approach would lead
5. Future research directions and challenges to a comprehensive understanding of TMJD and the development of
effective treatments for this complex disorder.
The research on TMJD encounters significant limitations and chal­
lenges owing to the complexity of this condition, warranting advanced 6. Conclusion
research for improving patient treatment outcomes. The pathophysi­
ology of TMJD is inherently multidimensional, involving various factors TMJD is a complex disorder that affects oral health and the overall
ranging from biological to psychological to social aspects. This diversity health status of an individual. The pathophysiological mechanisms of
renders it challenging to identify a single factor responsible for the TMJD are linked intricately to multiple disciplines, including neurosci­
development of TMJD, adding to the layers of complexity of this con­ ence, dentistry, and psychology. Neuroscience enables the exploration
dition and rendering the relevant research further challenging (Kapos of the transmission, perception, and modulation mechanisms of pain
et al., 2020). Moreover, despite extensive efforts to explore the epide­ signals, thereby providing a crucial perspective for understanding the
miology of TMJD pain, numerous challenges are encountered, for complexity of TMJD. Advances in neuroscience have led to the emer­
instance, due to the common use of stimulant injections into the TMJ gence of novel therapeutic approaches such as neuromodulation and
space in acute pain studies, which might not entirely simulate the actual biofeedback, which have demonstrated great potential in TMJD treat­
manifestation of chronic pain in humans (Almarza, 2018). Therefore, ment by offering the advantages of non-invasive and personalized
future research has to adopt novel approaches and techniques, such as treatment approaches to patients with TMJD. However, TMJD research
focusing more on the functional changes in the pain network and the and treatment continue to encounter several challenges to this day,
default mode network, to obtain deeper insights into the neurobiological necessitating interdisciplinary collaboration and innovative research
basis of TMJD (Festa et al., 2021). In addition, mechanical perturbation approaches for addressing the concerns. Future research should, there­
models that are closer to the actual manifestation of TMJD in humans, fore, further intensively explore the neurophysiological mechanisms of
such as a sustained mouth-opening study to determine the risk factors TMJD to develop further effective treatment strategies and provide
for TMJD development, could provide further accurate disease simula­ comprehensive, integrated diagnostic and treatment plans to patients
tion and therapeutic efficacy assessment (Almarza, 2018). Innovative with TMJD through the cooperation of interdisciplinary teams. In
explorations and novel research directions should be considered, and in summary, neuroscience plays an indispensable role in understanding
this regard, stem cell therapy and tissue engineering could offer fresh TMJD and, consequently, treating the condition. The findings attained
hope for the treatment of refractory patients. On the other hand, precise through this field, therefore, have the potential to advance the treatment
measurement and analysis of the masticatory function using surface of TMJD while also contributing to enhancing the quality of life of pa­
electromyography could provide a fresh perspective in the assessment of tients and effectively utilizing the available medical resources.
the masticatory dysfunction associated with TMJD and a deeper un­
derstanding of the impact of TMJD (Da Silva et al., 2023). In order to CRediT authorship contribution statement
ensure that patients with TMJD benefit from future research on this
condition, a broader range of clinical trials and multicenter studies have Guofang Lu: Writing – original draft, Funding acquisition. Rui Du:
to be conducted to assess the applicability and effectiveness of various Writing – review & editing.
treatment methods across different patient populations. Moreover, to
promote comprehensive development in the treatment and management

6
G. Lu and R. Du Archives of Oral Biology 164 (2024) 106001

Declaration of Competing Interest Craniomandibular Practice, 41(6), 550–555. https://doi.org/10.1080/


08869634.2021.1883364
Gauer, R. L., & Semidey, M. J. (2015). Diagnosis and treatment of temporomandibular
None. disorders. American Family Physician, 91(6), 378–386.
Grenga, V., Schiavoni, R., & Lubrano, C. (2004). Osteoarthritis of the temporomandibular
joint in an adult patient with Hashimoto thyroiditis: case report [Case Reports;
Acknowledgments
Journal Article]. World Journal of Orthodontics, 5(3), 254–259.
Hogrefe, N., Blom, S. M., Valentinova, K., Ntamati, N. R., Jonker, L., Nevian, N. E., &
This work was supported by grants from the National Natural Science Nevian, T. (2022). Long-lasting, pathway-specific impairment of a novel form of
Foundation of China (82303426). spike-timing-dependent long-term depression by neuropathic pain in the anterior
cingulate cortex. The Journal of Neuroscience, 42, 2166–2179. https://doi.org/
10.1523/JNEUROSCI.0326-21.2022
Author contributions Janevic, M. R., Mathur, V. A., Booker, S. Q., Morais, C., Meints, S. M., Yeager, K. A., &
Meghani, S. H. (2022). Making pain research more inclusive: Why and how. The
Journal of pain, 23(5), 707–728. https://doi.org/10.1016/j.jpain.2021.10.004
Guofang Lu designed and wrote the manuscript. Rui Du revised the Jung, A., Shin, B. C., Lee, M. S., Sim, H., & Ernst, E. (2011). Acupuncture for treating
manuscript and managed the whole procedure. All authors participated temporomandibular joint disorders: a systematic review and meta-analysis of
randomized, sham-controlled trials [Journal Article; Meta-Analysis; Research
in the discussion of the results and the final revision of the manuscript. Support, Non-U.S. Gov’t; Review; Systematic Review]. Journal of Dentistry, 39(5),
341–350. https://doi.org/10.1016/j.jdent.2011.02.006
References Kapos, F. P., Exposto, F. G., Oyarzo, J. F., & Durham, J. (2020). Temporomandibular
disorders: A review of current concepts in aetiology, diagnosis and management.
Oral Surgery, 13(4), 321–334. https://doi.org/10.1111/ors.12473
Acharya, S., Pradhan, A., Chaulagain, R., & Shah, A. G. (2018). Temporomandibular joint
Kellenberger, C. J., Bucheli, J., Schroeder-Kohler, S., Saurenmann, R. K., Colombo, V., &
disorders and its relationship with parafunctional habits among undergraduate
Ettlin, D. A. (2019). Temporomandibular joint magnetic resonance imaging findings
medical and dental students. Journal of College of Medical Sciences-Nepal, 14(3).
in adolescents with anterior disk displacement compared to those with juvenile
https://doi.org/10.3126/jcmsn.v14i3.20289
idiopathic arthritis. Journal of Oral Rehabilitation, 46(1), 14–22. https://doi.org/
Akkemik, Ö., Kugel, H., & Fischbach, R. (2022). Acute soft tissue injury to the
10.1111/joor.12720
temporomandibular joint and posttraumatic assessment after mandibular condyle
Kobayashi, K., Jokaji, R., Miyazawa-Hira, M., Takatsuka, S., Tanaka, A., Ooi, K.,
fractures: A longitudinal prospective MRI study. Dento Maxillo Facial Radiology, 51
Nakamura, H., & Kawashiri, S. (2017). Elastin-derived peptides are involved in the
(3), Article 20210148. https://doi.org/10.1259/dmfr.20210148
processes of human temporomandibular disorder by inducing inflammatory
Almarza, A. J. (2018). Mechanical perturbation model of temporomandibular joint
responses in synovial cells. Molecular Medicine Reports, 16, 3147–3154. https://doi.
disorders and assessment of musculature. Pain, 159(7), 1181–1182. https://doi.org/
org/10.3892/mmr.2017.7012
10.1097/j.pain.0000000000001228
Kothari, S. F., Baad Hansen, L., Oono, Y., & Svensson, P. (2015). Somatosensory
Andre, A., Kang, J., & Dym, H. (2021). Pharmacologic treatment for temporomandibular
assessment and conditioned pain modulation in temporomandibular disorders pain
and temporomandibular joint disorders. Oral and Maxillofacial Surgery Clinics of
patients. Pain, 156, 2545–2555. https://doi.org/10.1097/j.pain.0000000000000325
North America.
Linley, J. E., Rose, K., Patil, M., Robertson, B., Akopian, A. N., & Gamper, N. (2008).
Barkhordarian, A., Chiappelli, F., & Demerjian, G.G. (2018). Neuroimmune and Systemic
Inhibition of M current in sensory neurons by exogenous proteases: A signaling
Manifestations of Neuroinflammation in the Temporomandibular Joint and Related
pathway mediating inflammatory nociception. The Journal of Neuroscience, 28(44),
Disorders http://doi.org/10.1007/978–3-319–76367-5_3.
11240–11249. https://doi.org/10.1523/JNEUROSCI.2297-08.2008
Becker, S., Navratilova, E., Nees, F., & Van Damme, S. (2018). Emotional and
Liou, Y. J., Bai, Y. M., Tsai, S. J., Chen, T. J., Chen, M. H., & Lo, W. L. (2023).
motivational pain processing: Current state of knowledge and perspectives in
Bidirectional Associations of Temporomandibular Joint Disorders with Major
translational research. Pain Research & Management, 2018. https://doi.org/10.1155/
Depressive and Anxiety Disorders. The Journal of Evidence-Based dental Practice, 23
2018/5457870
(2), Article 101860. https://doi.org/10.1016/j.jebdp.2023.101860
Breton-Torres, I., Trichot, S., Yachouh, J., & Jammet, P. (2016). Temporomandibular
List, T., & Jensen, R. H. (2017). Temporomandibular disorders: Old ideas and new
joint disorders: Physiotherapy and postural approaches] [Journal Article; Review.
concepts. Cephalalgia, 37, 692–704. https://doi.org/10.1177/0333102416686302
Revue Délelő tt stomatologie, Délelő tt Chirurgie maxillo-faciale et Délelő tt Chirurgie Orale,
Mamet, J., Lazdunski, M., & Voilley, N. (2003). How nerve growth factor drives
117(4), 217–222. https://doi.org/10.1016/j.revsto.2016.07.012
physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory
Chichorro, J. G., Porreca, F., & Sessle, B. J. (2017). Mechanisms of craniofacial pain.
neurons. The Journal of Biological Chemistry, 278(49), 48907–48913. https://doi.org/
Cephalalgia, 37, 613–626. https://doi.org/10.1177/0333102417704187
10.1074/jbc.M309468200
Chung, M., & Ro, J. Y. (2020). Peripheral glutamate receptor and transient receptor
Marks, D. M., Shah, M. J., Patkar, A. A., Masand, P. S., Park, G. Y., & Pae, C. U. (2009).
potential channel mechanisms of craniofacial muscle pain. Molecular Pain, 16.
Serotonin-norepinephrine reuptake inhibitors for pain control: Premise and promise.
https://doi.org/10.1177/1744806920914204
Current Neuropharmacology, 7(4), 331–336. https://doi.org/10.2174/
Criado, L. F., de la Fuente, A., Heredia, M., Montero, J., Albaladejo, A., & Criado, J. M.
157015909790031201
(2016). Electromyographic biofeedback training for reducing muscle pain and
Matheson, E. M., Fermo, J. D., & Blackwelder, R. S. (2023). Temporomandibular
tension on masseter and temporal muscles: A pilot study. Journal of Clinical and
disorders: Rapid evidence review. American Family Physician, 107(1), 52–58. https://
Experimental Dentistry, 8, e571–e576.
doi.org/10.1177/0333102417704187
Crow, H.C., Khawaja, S.N., Mahmoud, R.F. G., Kartha, K., Mccall, W.D., & Gonzalez, Y.M.
McCarberg, B., & Peppin, J. (2019). Pain pathways and nervous system plasticity:
(2017). Association between arthralgia and imaging findings of effusion in the
Learning and memory in pain. Pain Medicine (Malden, Mass ), 20(12), 2421–2437.
temporomandibular joints.
https://doi.org/10.1093/pm/pnz017
Da Silva, Z. A., Melo, W. W. P., Ferreira, H. H. N., Lima, R. R., & Souza-Rodrigues, R. D.
Nascimento, G. C., de Paula, B. B., Gerlach, R. F., & Leite-Panissi, C. R. A. (2021).
(2023). Global trends and future research directions for temporomandibular
Temporomandibular inflammation regulates the matrix metalloproteinases MMP-2
disorders and stem cells. Journal of Functional Biomaterials, 14(2), 103. https://doi.
and MMP-9 in limbic structures. Journal of Cellular Physiology, 236, 6571–6580.
org/10.3390/jfb14020103
https://doi.org/10.1002/jcp.30341
Dashnyam, K., Lee, J., Mandakhbayar, N., Jin, G., Lee, H., & Kim, H. W. (2018). Intra-
Noiman, M., Garty, A., Maimon, Y., Miller, U., & Lev-Ari, S. (2010). Acupuncture for
articular biomaterials-assisted delivery to treat temporomandibular joint disorders.
treating temporomandibular disorder: Retrospective study on safety and efficacy
Journal of Tissue Engineering, 9. https://doi.org/10.1177/2041731418776514
[Journal Article]. Journal of Acupuncture and Meridian Studies, 3(4), 260–266.
De Rossi, S. S., Greenberg, M. S., Liu, F., & Steinkeler, A. (2014). Temporomandibular
https://doi.org/10.1016/S2005-2901(10)60046-5
disorders: Evaluation and management. The Medical Clinics of North America, 98(6),
Ok, S. M., Kim, J. H., Kim, J. S., Jeong, E. G., Park, Y. M., Jeon, H. M., Heo, J. Y.,
1353–1384. https://doi.org/10.1016/j.mcna.2014.08.009
Ahn, Y. W., Yu, S. N., Park, H. R., Kim, K. H., Ahn, S. C., & Jeong, S. H. (2020). Local
Dolwick, M. F., & Freburg-Hoffmeister, D. L. (2019). Disturbances of the
injection of growth hormone for temporomandibular joint osteoarthritis [Journal
temporomandibular joint apparatus. Evidence-Based Oral Surgery, 399–421.
Article]. Yonsei Medical Journal, 61(4), 331–340. https://doi.org/10.3349/
Dutra Dias, H., Botelho, A. L., Bortoloti, R., & Dos Reis, A. C. (2021). Neuroscience
ymj.2020.61.4.331
contributes to the understanding of the neurobiology of temporomandibular
Ong, W., Stohler, C. S., & Herr, D. R. (2018). Role of the Prefrontal Cortex in Pain
disorders associated with stress and anxiety. Cranio: the Journal of Craniomandibular
Processing. Molecular Neurobiology, 56, 1137–1166. https://doi.org/10.1007/
Practice, 1–6. https://doi.org/10.1080/08869634.2021.1977901
s12035-018-1130-9
Ferrillo, M., Giudice, A., Marotta, N., Fortunato, F., Di Venere, D., Ammendolia, A.,
Ouanounou, A., Goldberg, M. B., & Haas, D. A. (2017). Pharmacotherapy in
Fiore, P., & de Sire, A. (2022). Pain management and rehabilitation for central
Temporomandibular Disorders: A Review Journal (Canadian Dental Association), 83, h7.
sensitization in temporomandibular disorders: A comprehensive review. International
Raison, C. L., & Miller, A. H. (2003). When not enough is too much: the role of
Journal of Molecular Sciences, 23(20). https://doi.org/10.3390/ijms232012164
insufficient glucocorticoid signaling in the pathophysiology of stress-related
Festa, F., Rotelli, C., Scarano, A., Navarra, R., Caulo, M., & Macrì, M. (2021). Functional
disorders. The American Journal of Psychiatry, 160(9), 1554–1565. https://doi.org/
magnetic resonance connectivity in patients with temporomadibular joint disorders.
10.1176/appi.ajp.160.9.1554
Frontiers in Neurology, 12, Article 629211. https://doi.org/10.3389/
Santiago, V., Janal, M. N., Cook, D. B., & Raphael, K. G. (2022). Temporal Summation
fneur.2021.629211
and Aftersensations of Second Pain in Women with Myofascial Temporomandibular
Gaş, S., Ekşi Özsoy, H., & Cesur Aydın, K. (2021). The association between sleep quality,
Disorder Differ by Presence of Temporomandibular Joint Pain. Journal of Pain
depression, anxiety and stress levels, and temporomandibular joint disorders among
Research, 15, 3275–3286. https://doi.org/10.2147/JPR.S381640
Turkish dental students during the COVID-19 pandemic. Cranio: the Journal of

7
G. Lu and R. Du Archives of Oral Biology 164 (2024) 106001

Scrivani, S. J., Keith, D. A., & Kaban, L. B. (2008). Temporomandibular disorders. The temporomandibular disorders. The Japanese Dental Science Review, 52, 93–106.
New England Journal of Medicine, 359(25), 2693–2705. https://doi.org/10.1056/ https://doi.org/10.1016/j.jdsr.2016.04.004
NEJMra0802472 Tashiro, A., & Bereiter, D. A. (2020). The effects of estrogen on temporomandibular joint
Shoohanizad, E., Garajei, A., Enamzadeh, A., & Yari, A. (2019). Nonsurgical management pain as influenced by trigeminal caudalis neurons. Journal of Oral Science, 62(2),
of temporomandibular joint autoimmune disorders. AIMS Public Health, 6(4), 150–155. https://doi.org/10.2334/josnusd.19-0405
554–567. https://doi.org/10.3934/publichealth.2019.4.554 Wieckiewicz, M., Boening, K., Wiland, P., Shiau, Y. Y., & Paradowska-Stolarz, A. (2015).
Silant’Eva, E. N. (2010). The role of therapeutic exercises in the combined treatment and Reported concepts for the treatment modalities and pain management of
rehabilitation of patients with pain syndrome associated with the dysfunction of temporomandibular disorders [Journal Article; Review]. The Journal of Headache
temporomandibular joint [English Abstract; Journal Article]. Voprosy kurortologii, and pain, 16, 106. https://doi.org/10.1186/s10194-015-0586-5
fizioterapii, i lechebnoi fizicheskoi kultury, (3), 22–26. Woolf, C. J. (2011). Central sensitization: Implications for the diagnosis and treatment of
Silva, T. D. S. F., & Galdino, M. K. C. (2017). The use of noninvasive neuromodulation in pain. Pain, 152(3 Suppl), S2–S15. https://doi.org/10.1016/j.pain.2010.09.030
the treatment of chronic pain in individuals with temporomandibular dysfunction. National Academies of Sciences, E. A. M., Medicine, H. A., Division, Services, B. O. H. C.,
Revista Dor, 18, 350–354. https://doi.org/10.5935/1806-0013.20170128 Policy, B. O. H. S., to, C. O. T. D., & Treatment, C.. (2020). Temporomandibular
Smith, J. L., Allen, J. W., Fleischer, C. C., & Harper, D. E. (2022). Topology of pain Disorders: Priorities for Research and Care. US: National Academies Press.
networks in patients with temporomandibular disorder and pain-free controls with Woolf, C. J. (2018). Pain amplification—A perspective on the how, why, when, and
and without concurrent experimental pain: A pilot study. Frontiers in Pain Research, where of central sensitization. Journal of Applied Biobehavioral Research, 23(2),
3, Article 966398. https://doi.org/10.3389/fpain.2022.966398 Article e12124. https://doi.org/10.1111/jabr.12124
Somvanshi, P. R., Mellon, S. H., Yehuda, R., Flory, J. D., Makotkine, I., Bierer, L., Youssef, A. M., Macefield, V. G., & Henderson, L. A. (2016). Cortical influences on
Marmar, C., Jett, M., & Doyle, F. R. (2020). Role of enhanced glucocorticoid receptor brainstem circuitry responsible for conditioned pain modulation in humans. Human
sensitivity in inflammation in PTSD: insights from computational model for Brain Mapping, 37(7), 2630–2644. https://doi.org/10.1002/hbm.23199
circadian-neuroendocrine-immune interactions. American Journal of Physiology Zhang, J., Li, X., Jin, Z., Liang, M., & Ma, X. (2018). Spontaneous brain activity and
Endocrinology and Metabolism, 319(1), E48–E66. https://doi.org/10.1152/ connectivity in female patients with temporomandibular joint synovitis pain: a pilot
ajpendo.00398.2019 functional magnetic resonance imaging study. Oral surgery, oral medicine, oral
Sousa, M. D. L. R., Mashuda, C. S., Sato, J. E., & Siqueira, J. T. T. (2014). Effects of pathology and oral radiology, 126(4), 363–374. http://doi.org/Spontaneous brain
acupuncture in adults with temporomandibular disorders. Revista Dor, 15, 87–90. activity and connectivity in female patients with temporomandibular joint synovitis
Staniszewski, K., Lygre, H., Bifulco, E., Kvinnsland, S., Willassen, L., Helgeland, E., pain: a pilot functional magnetic resonance imaging study.
Berge, T., & Rosén, A. (2018). Temporomandibular disorders related to stress and Zuszek, A., Borek, J. M., Malak, R. E., & Samborski, W. (2019). Temporomandibular joint
HPA-axis regulation. Pain Research & Management, 2018. https://doi.org/10.1155/ dysfunctions in the context of psychological disorders among pediatric patients.
2018/7020751 Journal of Education, Health and Sport, 9(12), 82–86. https://doi.org/10.12775/
Suenaga, S., Nagayama, K., Nagasawa, T., Indo, H. P., & Majima, H. J. (2016). The JEHS.2019.09.12.009
usefulness of diagnostic imaging for the assessment of pain symptoms in

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