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mini-review

J. Stomat. Occ. Med. (2008) 1: 5157


DOI 10.1007/s12548-008-0010-8
Printed in Austria
Springer-Verlag 2008

The masticatory organ and stress management


S. Sato1 , R. Slavicek2

1
Department of Craniofacial Growth and Development Dentistry, Division of Orthodontics,
Kanagawa Dental College, Yokosuka, Japan
2
Danube University Krems, Austria

Received September 20, 2008; Accepted October 1, 2008

In humans, the strong grinding and clenching function of the oral structures. In addition to mastication, the masticatory
masticatory muscles known as bruxism has been thought organ plays essential roles in speech, respiration, swallowing,
to play an important role in mitigating stress-induced psy- maintaining posture, and stress management through the
chosomatic disorders by down-regulating the limbic system, clenching and grinding of bruxism. Therefore, dentists must
the autonomic nervous system, and the hypothalamic-pitui- observe more than just the static t of upper and lower teeth as
tary-adrenal axis. Experimental research results showed that they diagnose and treat stomatognathic disorders, and they
bruxism-like activity has benecial effects on stress-induced must recognize that they are custom-tailoring treatments to
reactions such as increasing expression of Fos protein, neu- the complex physiological system of each individual.
ronal nitric oxide synthase, phosphorylated extracellular sig- The masticatory organ is closely related to the brains
nal-regulated kinase 1/2, corticotropin-releasing factor, and limbic system and to express emotions as a functional unit.
free radicals in the paraventricular nucleus of hypothalamus, Therefore, we look forward to the day when dental practi-
alterations in the blood neutrophil/lymphocyte ratio and tioners view stress medicine and dental occlusion as two parts
adrenocorticotropic hormone level, and stomach ulcer for- of an integrated whole a eld of study in which two concepts
mation in animal studies, as well as increasing amygdala play central roles: the concept of a centrally regulated feed-
neuronal activity and salivary chromogranin A level in human back control system and the concept of the stress bruxism
studies. All of these ndings strongly suggest that bruxism-like axis. The role of the masticatory organ as a stress release valve
activity of the masticatory organ has the ability to decrease must be recognized as the most important component of
stress-induced allostatic overload. The health of the mastica- occlusion dentistry [13].
tory organ depends critically on occlusion, which must be of
sufcient quality to successfully carry out its important role in
managing stress. Occlusion and the brain must function in Aggression and the masticatory organ
harmony. For these reasons, we must integrate the study of The limbic system has been described in reference to emo-
occlusion into the broader scope of medical science; in so tionally related areas of the brain and the pathway that
doing, we will meaningfully advance the state of the art of interconnects them. These areas are generally composed of
dental care and general health care. sites that function to alter emotions. Therefore, the mastica-
Keywords: Bruxism, stress, masticatory organ, brain, tory organ is considered to be directly or indirectly related to
allostasis the limbic system. Modern humans retain this connection;
however, this organ is more frequently used for the expression
of aggression in the form of sleep bruxism, because the newly
Introduction developed brain cortex suppresses aggressive behavior in
modern humans.
The human body is a set of parts so related and interconnected
Interestingly, according to phylogenesis, many animal
as to form an organic whole. It is considered a functioning
species grind their teeth as a component of their response to a
organism with a number of bodily organs acting together to
threatening or stressful situation. Every [4, 5] proposed that
perform all of the functions necessary for life and health. The
animals use their teeth and jaws as weapons to bite and kill,
masticatory organ is a unique system in the body from
and as tools to divide, hold, and snarl. The primitive hominoid,
physiological and psychosomatic points of view. The normal
particularly in the pre-tool era, would have immediately
process of mastication consists of a series of highly coordinat-
extruded his mandible laterally when facing an appropriate
ed movements of the lower and upper jaws, lips, cheeks,
stress situation. Although this action in civilized Homo sapiens
tongue, temporomandibular joints, and other oral and peri-
has been apparently eliminated as instinctual, it nevertheless
occurs during sleep.
Correspondence: Sadao Sato, Research Center of Brain and Oral Science,
Kanagawa Dental College, 82 Inaoka-Cho, Yokosuka 238-8580, Japan. The human masticatory organ has evolved over a long
E-mail: satos@kdcnet.ac.jp period into an organ for emotional management, having

J. Stomat. Occ. Med. The masticatory organ and stress management 1/2008 51
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passed through stages in which the organ was used predomi- concepts of occlusion slowly shifted to concepts based on the
nantly as a tool or as a weapon for expressing aggression. It parafunctions of masticatory organ, grinding and clenching
was suggested that modern humans still use the masticatory [30]. Therefore, it must be considered that these loads con-
organ when they are psychologically stressed to express tribute to many oral diseases [31, 32]; that is, excessive loads
aggression, but it has evolved from a direct expression of cause periodontal breakdown in some cases, and hard tissue
aggression to an indirect expression such as clenching or breakdown or temporomandibular disorders in other cases.
grinding the teeth. In this context, it is necessary to investigate the inuences
Extensive research has shown that psychic stress and of bruxism with excessive masticatory muscle activity on the
occlusal disharmony are related to bruxism [611]. From a following three components: tooth structure (non-carious
psychosomatic point of view, unresolved psychic problems cervical lesions, hypersensitivity, wear, and cracks); periodon-
are transferred to the level of organs. Utilizing the masticatory tal tissue (attachment level, mobility, bleeding on probing,
organ as a stress outlet organ is an efcient and risk-free and exostosis); and craniomandibular structure (muscle and
solution to the problem of stress management. TMJ). It is also crucial to determine the conditions that cause
From this point of view, the functions of the masticatory damage to specic structures or tissues.
organ are intimately connected with functions of the brain, Mehta et al. [33] documented the inter-relationship
both somatically and psychically. The masticatory organ ap- among indices of periodontal breakdown (Russell Periodontal
pears to be basic and necessary to the entire organism and its Index) [34], temporomandibular dysfunction (Helkimo Dys-
role within its environment. function Index) [35], tooth wear assessment, and parafunc-
tional activity based on the reports of sleep bruxism. About
90% of subjects with moderate and severe bruxism scores had
Bruxism and oral disease
a high index in only one of the three parameters, suggesting
Bruxism is dened as a diurnal or nocturnal parafunctional that the weakest component of the oral system is selectively
activity including clenching, grinding, and gnashing of the affected by strong parafunctional activity. They called it the
teeth. Because sleep bruxism occurs in most humans, sleep Weak Link Theory. Current results [36, 37] also suggested
bruxism is a physiological activity that may be a necessary that bruxism with molar contacts was responsible not only
function or behavior of the human body [1215]. Lavigne et al. for the diseases affecting the teeth and periodontal structures,
[16] reported that the rhythmic masticatory muscle activity but also for TMJ dysfunction, which partly supports the Weak
during sleep was related to certain sleep-related physiological Link Theory.
functions, including autonomic activation. Results clearly
showed that rhythmic masticatory muscle activity was not
associated with the disruption of nocturnal sleep, further Effects of bruxism-like activity in animal studies
suggesting that this motor activity is a natural activity occur- During the process of evolution, animals have long used the
ring during sleep. Because sleep bruxism with excessive masticatory organ as an emotional outlet besides its use as a
muscle activity may damage the oral tissues and cranioman- simple tool for chewing food [4, 5]. In evolution to primates,
dibular system, it has become an important research subject there is found a dramatic change in Quantitative comparison
in clinical dentistry. of the amygdala in insectivores and primates [38]. The aggres-
Tremendous occlusal forces from bruxism activity, sive zentromedian parts are strongly reduced in comparison
which may be signicantly greater than those of conscious with the Centro-basic-lateral parts of N. amygdale (pleasure
efforts by an individual during waking hours, are applied oriented). Therefore, the conscious life-defensive aggres-
to teeth and periodontal tissues during sleep bruxism. Con- sive patterns are more and more reduced to unconscious
sequently, signicant loads are distributed to the dentition, movements like clenching and bruxing.
the periodontal supporting structures, and the temporo- Many animal species grind their teeth as a component
mandibular joint (TMJ). of their response to a threatening or stressful situation. It
A new classication of dental hard tissue lesions was has been suggested that modern humans still use the
introduced as abfraction, which is used to designate stress- masticatory organ to express aggression if they are over-
induced lesions that result from hyperfunction and parafunc- whelmed psychologically. Utilizing the masticatory organ
tion [1723]. Both tensile and shearing forces contribute to as a stress outlet is an efcient, risk-free solution to the
the loss of hydroxyapatite crystals in the cervical region during problem of stress management [13]. Several pieces of evid-
active lesion formation. The location and distribution of ence using animal models were proposed in recent years,
abfractive lesions support this tensile stress-induced bio- in which an activity of the masticatory organ showed an
mechanical theory. Drum [24] reported that traumatizing attenuating effect on stress-induced neurophysiological
parafunction played a dominant role in the development of events as described below.
periodontal diseases. Bruxism activity is also considered to be
a signicant contributing factor to repetitive overloading of
Stress-induced tissue reactions
the structures of the TMJ [25]. In the eld of dental research,
however, there have long been controversial discussions It has been found that experimental rats grind their teeth
regarding the relationships between occlusion and oral dis- spontaneously as a component of their response to a re-
eases such as TMJ disorders and periodontal diseases. strained stress condition [38], and many research results
Because it was clear that tremendous occlusal forces were showed that bruxism-like activity (BLA) prevented stress-
exerted by parafunctional bruxism activity, which very much induced stomach ulcer formation [3944], suggesting the use
depends upon the occlusion schemes [2629], contemporary of the masticatory organ to relieve stress (Fig. 1).

52 1/2008 The masticatory organ and stress management J. Stomat. Occ. Med.
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Fig. 1: Hypothetical model of stress management using the masticatory


organ. The masticatory organ can be used as a tool for emotional outlet,
by whose transferences the unresolved psychic problems to the somatic
system are prevented. Utilizing the masticatory organ for stress man-
agement is relatively free of risk

In rats, the plasma adrenocorticotropic hormone level


was increased 30 min after undergoing restraint stress, while
BLA attenuated the adrenocorticotropic hormone level.
The neutrophil/lymphocyte ratio was reversed only 240 min
after restraint stress application, which might be caused by a
damage to the internal organs such as the stomach, thymus,
Fig. 2: The effects of BLA on core temperature rise caused by restraint
and spleen [4547]. All these stress-induced alterations of
stress. Thermal infrared images were compared to visualize the changes
physiological parameters were attenuated by BLA in a dura- in the surface temperature in stressed and stress-BLA rats. BLA attenu-
tion-dependent manner. The results suggested that the reac- ates stress-induced increasing body temperature
tions of the hypothalamus-pituitary-adrenal (HPA) axis and
the sympathetic nervous system to the stress were regulated
by BLA of the masticatory organ. activity, such as biting a wooden stick (simulated BLA), might
Another animal study with rats to investigate the effects affect restraint-induced Fos protein expression in the rat brain
of BLA on high blood pressure, increasing core temperature, stem.
and chemical mediator accumulation in the serum induced Using immunohistochemical methods to detect Fos pro-
by restraint stress showed that BLA during restraint sig- tein, the effects of acute restraint stress and BLA on the
nicantly reduced these parameters compared with those neuronal circuits in the rat central nervous system were shown
of rats that did not perform BLA [48]. Differences in body [55]. Results showed that the restraining rats in the supine
temperature were visible in infrared thermal images of the position for 1060 min invariably induced rapid expression of
restraint-only and restraint-with-BLA rats (Fig. 2). Biochem- Fos protein in subsets of neurons in the somatosensory and
ical analysis revealed that biting signicantly suppressed motor cortices, paraventricular hypothalamic nucleus (PVN),
plasma interleukin-1b, interleukin-6, and leptin and that it locus coeruleus (LC), medial amygdaloid nucleus, and ante-
signicantly increased thyroid-stimulating hormone. These rior portion of the paraventricular thalamic nucleus. The
data suggest that BLA is a possible behavioral coping skill suppression of Fos immunoreactivity by BLA during restraint
that enables an organism to reduce allostatic load. provides further support for the assumption that parafunc-
tional masticatory activity attenuates adverse effects of psy-
chological stress on the central nervous system.
Fos expression in brain
Animal experiments have shown that BLA signicantly at-
Corticotropin-releasing factor
tenuates stress-induced increases in noradrenaline (norepi-
nephrine) turnover in the hypothalamus, limbic areas, and Stress-induced activation of the HPA axis is characterized by
amygdala [4953]. Moreover, nonfunctional masticatory ac- enhanced expression of corticotropin-releasing factor (CRF)
tivity attenuates the increase in striatal dopaminergic activity in the PVN and the consequent increases in adrenocortico-
caused by stressors [8, 11]. It has been shown that psycho- tropic hormone and adrenal glucocorticoid in the plasma.
logical stress such as restraint or immobilization of the Thus, the CRF expressed in the hypothalamus plays an
animals induces the activation of c-fos and the expression important role in mediating behavioral responses to stres-
of the Fos protein in subsets of neurons in the central nervous sors. The number of CRF-expressing neurons in the PVN
system [54]. It was of particular interest whether masticatory increased signicantly after a short-time restraint (30 or 60

J. Stomat. Occ. Med. The masticatory organ and stress management 1/2008 53
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min) followed by a 180-min postrestraint period. BLA during and ESR-computed tomography (ESR-CT) imaging were
the restraint stress signicantly suppressed the restraint- used to show that the decay rate of MC-PROXYL in the
induced enhancement of CRF expression in the PVN [56]. hypothalamus of isolated brain after 30 min of restraint
Therefore, it is speculated that the suppression of central stress was more rapid than in unrestrained control rats, which
noradrenergic transmission, including the afferent pathway would suggest that restraint was associated with oxidative
mediated by LC, might be the mechanism by which CRF is stress [59]. BLA suppresses oxidative stress induced by
suppressed by BLA. restraint stress and the anti-stress effect of BLA is important
for reducing the adverse effects associated with exposure to
psychological stressors.
Neuronal nitric oxide synthase
The effect of BLA during restraint stress on nitric oxide
Nitric oxide modulates the activity of the endocrine system in levels in the hypothalamus was examined using a nitric oxide
the behavioral response to stress. The effect of restraining the selective electrode [60]. The levels of nitric oxide were in-
body of an animal on the expression of neuronal nitric oxide creased by restraint stress and this increase was prevented by
synthase (nNOS) in the PVN of the hypothalamus and the BLA for 30 min, suggesting that there is an anti-stress effect of
inhibitory effect of BLA on restraint-induced nNOS expres- BLA.
sion were investigated [57]. An increase in nNOS mRNA
expression and nNOS-positive neurons in the rat hypothala-
mus was observed after 30 or 60 min of restraint stress. BLA Brain-derived neurotrophic factor (BDNF)
during bodily restraint decreased nNOS mRNA expression in Brain-derived neurotrophic factor (BDNF) is the most abun-
the hypothalamus. In addition, the number of nNOS-positive dant neurotrophin in the central nervous system, and it is
neurons was signicantly reduced in the PVN of the hypo- closely involved in survival, maintenance, and neural trans-
thalamus. These observations clearly suggest a possible anti- mission in neural cells. Acute restraint stress for 60 min
stress effect of BLA and how this mechanism might be signicantly increased the level of plasma BDNF [61], and it
unconsciously operating during exposure to psychological was suggested that the salivary gland is a primary source of
stressors.
plasma BDNF in the condition of acute stress [62]. The BLA
also increased BDNF mRNA and plasma BDNF, suggesting
Phosphorylation of extracellular signal-regulated protein that BDNF derived from the salivary gland provides protective
kinase 1/2 effects against damage from acute stress [63]. It was also
reported that BLA inuences the alterations in BDNF levels
As described above, acute immobilization stress induces Fos induced by acute stress in rat hippocampus [64].
expression, which is generally used as a marker for neuronal Table 1 illustrates the results from animal studies that
activity. It has been suggested that Fos expression may be have used rats as a stress model.
linked to the phosphorylation of extracellular signal-regulated
protein kinase 1/2 (pERK1/2) in the hypothalamic PVN. An
immunohistochemical study was designed to determine
whether acute immobilization stress induces pERK1/2 in the Effects of bruxism-like activity in human studies
PVN and if the stress-induced pERK1/2 is attenuated by
Functional magnetic resonance imaging
simultaneous BLA behavior [58]. Acute immobilization stress
in up to 15-min increments produced detectable amounts of A close relationship between the masticatory function and the
pERK1/2 that were proportional to the duration of the stress. brain hippocampus activity and stress events has been de-
BLA during the acute immobilization stress signicantly re- scribed [6568]. The amygdala is reported to trigger physio-
duced the amount of detectable pERK1/2. These results logical changes in response to a stressful situation [51, 55]. If
suggest that BLA during acute stress inhibits pERK1/2 in this this is true, when the subject encounters a stressful situation,
region of the brain. It is feasible that the neuronal cellular the amygdala should be activated. To test this hypothesis, an
response to acute stress is regulated, in some part, by pERK1/2 auditory stimulus (a warning sound) was delivered to the
inhibition due to biting. subject through an earphone and blood oxygenation level
dependent (BOLD) signals were measured using functional
magnetic resonance imaging (fMRI) [69]. Because a stressor
Free radicals in the brain
may be perceived differently by different individuals, it was
Free radical reactions are involved in oxidative stress mediat- conrmed that the warning sound was, in fact, stressful to the
ed alterations in various physiological conditions. Because subjects. When the BOLD signals were statistically analyzed at
electron spin resonance (ESR) has been recognized as P 0.01, the amygdala was markedly activated and reactive
one of the most powerful techniques for detecting free radicals by this stimulus. However, when the subject chewed gum or
in biological tissues and cells, an ESR-based technique was clenched the teeth (BLA) under the same stress condition,
developed to detect free radical reactions in vivo. In vivo stress-induced activation was mostly avoided. Because the
ESR spectroscopy and ESR imaging can be used to major efferents of the amygdala include projections to the
investigate redox status in living organisms noninvasively and septum and hypothalamus, providing not only a subcortical
in real time. link for integrating limbic evaluative functions but also the
A bloodbrain barrier-permeable nitroxyl spin probe, switched HPA axis. Chewing is also associated with a similar
3-methoxycarbonyl-2,2,5,5,-tetramethylpyrrolidine-1-oxyl (MC- response but reduced to stress in the amygdala, thereby
PROXYL), was administered to rats, after which L-band ESR decreasing stress-stimulated hormonal activity.

54 1/2008 The masticatory organ and stress management J. Stomat. Occ. Med.
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Tab. 1. Summary the effects of BLA studies have identied selective localization of CgA in sympa-
on the stress-induced alterations thetic nerves and radioimmunoassays measuring the secre-
of Allostatic parameters tion of CgA in saliva have been used to evaluate stress
conditions [70, 71]. Strong immunoreactivity of CgA in human
Parameters Change Effect Refs. salivary glands has been observed in the saliva matrix of ductal
by stress of BLA cavities and CgA has been shown to be produced predomi-
Brain nantly by serous cells and secreted into saliva [72].
In a study using 44 healthy adult volunteers, salivary CgA
Fos (PVN)1 increase attenuation [55] was measured by an enzyme-linked immunosorbent assay
(LC)2 increase attenuation [55] (ELISA) using antibody against synthetic human CgA [73]. The
results demonstrated the possibility of evaluating stress levels
(Thalamus) increase attenuation [55]
of individuals by measuring salivary CgA. Salivary CgA re-
(Amygdala) increase attenuation [55] sponds to psychosomatic stress. Bruxism-like grinding activity
3
CRF (PVN) increase attenuation [56] prevented a stress-induced increase in salivary CgA, suggest-
4
ing that the reaction of the parasympatheticadrenomedullary
nNOS (PVN) increase attenuation [57]
system is regulated by the BLA of the masticatory organ.
Free radicals increase attenuation [59]
ERK1/25 increase attenuation [60]
Allostasis and the masticatory organ
6
NO (Hippocampus) increase increase [58]
Allostasis refers to the adaptive processes that protect the body
BDN F7 increase increase [64] by responding to internal and external stress through systems
(Hippocampus)
such as the autonomic nervous system, the hypothalamic-
Blood pituitary-adrenal (HPA) axis, and immune systems [74, 75]. In
Lymphocyte decrease increase [4244] these allostatic processes, epinephrine, cortisol, and other
chemical messengers not only promote adaptation during the
Neutrophiles increase attenuation [4244] aftermath of acute stress, but also contribute to allostatic
ACTH8 increase attenuation overload the wear-and-tear on the body and brain that
results from being stressed. This conceptual framework has
Leptin increase attenuation [48]
created the need to know how to improve the efciency of the
IL1-b increase attenuation [48] adaptive response to stressors while minimizing overactivity
IL-6 increase attenuation [48] of the same systems, because such overactivity results in many
of the common diseases of modern life.
TSH9 increase attenuation [48]
The terms allostasis and allostatic overload allow a
10
ADR increase attenuation [4244, 52] more restricted, precise description instead of the overused
Cortisol increase attenuation [4244]
word stress and provide a view of how the essential protec-
tive and adaptive effects of physiological mediators that main-
Organ tain homeostasis are involved in the cumulative effects of daily
Spleen atrophy prevention [4244] life when they are overloaded. Inactivation of challenge nor-
mally returns the systems to baseline levels; however, if there
Thymus atrophy prevention [4244]
is over-exposure to stress, cumulative changes that lead to
Stomach ulcer formation prevention [3944, 52] potential overloading of the body and brain occur and may
Salivary Cg A 11
increase attenuation [73] result in different patho-physiological consequences.
The experimental results presented here suggest that the
Salivary BDNF increase increase [63] masticatory activity plays a major role in affecting the stress-
Body temperature increase attenuation [48] induced psychosomatic disorders by down-regulating the
limbic system, the HPA axis, the autonomic nervous system,
Blood pressure increase attenuation [48]
and the immune system. Therefore, the occlusion of the
Blood glucose increase attenuation [4244] masticatory organ contributes signicantly to the individuals
ability to manage allostasis. Bruxism in proper dentition can be
1
PVN Paraventricular nucleus, 2LC locus coeruus, 3CRF corticotropin releasing
factor, 4nNOS neuronal nitric oxiide synthese, 5ERK1/2 extracellular signal- recognized as a prophylactic system for stress-related diseases
regulated protein kinase 1/2, 6NO nitric oxide, 7BDNF brain-derived neuro- (allostatic overload). At the same time, we should keep in mind
trophic factor,8 ACTH adrenocorticotrophic hormone, 9TSH thyroid stimulating that the masticatory organ has long been directly related to the
hormone, 10ADR adrenaline,11chromogranine A limbic system and is used to express aggression; thus, this
organ is strongly related to the emotional state of human life.

Salivary chromogranin A
Conclusion
Chromogranin A (CgA) is a 48-kDa acidic, hydrophilic protein
that was originally isolated from chromafn granules of the This overview and the research ndings presented here em-
bovine adrenal medulla. Later, CgA was found ubiquitously phasize that the masticatory organ integrates a broad range of
in the secretory vesicles of neuroendocrine cells. Previous biological functions. The health of the masticatory organ

J. Stomat. Occ. Med. The masticatory organ and stress management 1/2008 55
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