Review

Cephalalgia
2017, Vol. 37(7) 692–704
Temporomandibular disorders: Old ideas ! International Headache Society 2017
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DOI: 10.1177/0333102416686302
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Thomas List1,2,3 and Rigmor Højland Jensen4

Abstract
Background: Temporomandibular disorders (TMD) is an umbrella term for pain and dysfunction involving the masti-
catory muscles and the temporomandibular joints (TMJs). TMD is the most common orofacial pain condition.
Its prominent features include regional pain in the face and preauricular area, limitations in jaw movement, and noise
from the TMJs during jaw movements. TMD affects up to 15% of adults and 7% of adolescents. Chronic pain is the
overwhelming reason that patients with TMD seek treatment. TMD can associate with impaired general health, depres-
sion, and other psychological disabilities, and may affect the quality of life of the patient.
Assessment: Evaluations indicate that the recently published Diagnostic Criteria for TMD (DC/TMD) are reliable and
valid. These criteria cover the most common types of TMD, which include pain-related disorders (e.g., myalgia, headache
attributable to TMD, and arthralgia) as well as disorders associated with the TMJ (primarily disc displacements and
degenerative disease). As peripheral mechanisms most likely play a role in the onset of TMD, a detailed muscle exam-
ination is recommended. The persistence of pain involves more central factors, such as sensitization of the supraspinal
neurons and second-order neurons at the level of the spinal dorsal horn/trigeminal nucleus, imbalanced antinociceptive
activity, and strong genetic predisposition, which also is included in DC/TMD.
Conclusion: The etiology is complex and still not clearly understood, but several biological and psychosocial risk factors
for TMD have been identified. Several studies indicate that patients with TMD improve with a combination of noninvasive
therapies, including behavior therapy, pharmacotherapy, physical therapy, and occlusal appliances. More stringently
designed studies, however, are needed to assess treatment efficacy and how to tailor treatment to the individual patient.

Keywords
Headache, orofacial pain, temporomandibular disorders, risk factors, management
Date received: 4 October 2016; revised: 22 November 2016; accepted: 30 November 2016

Introduction other chronic pain conditions  such as chronic

Temporomandibular disorders (TMD) is a collective
term for pain and dysfunction of the masticatory
muscles and temporomandibular joints (TMJs). Its
most common features are regional pain in the face
and preauricular area, limitations in jaw movements,
and noises from the TMJs during jaw movements (1).
The most common types of TMD include pain-related
disorders (e.g., myalgia, headache attributed to TMD,
and arthralgia) and disorders associated with the
TMJ (primarily disc displacements and degenerative
diseases) (2).
Chronic pain is the overwhelming reason for seeking
TMD treatment, while TMD may also be associated
with impaired general health, depression, or other psy-
chological disabilities that affect the patient’s wellbeing
and quality of life (3). TMD shares similarities with
tension-type headache or migraine, low back pain,
and fibromyalgia  and causes much suffering for the
individual (4). The economic burden on society of
1
Department of Orofacial Pain and Jaw Function, Faculty of Odontology,
Malmö University, Malmö, Sweden
2
Scandinavian Center for Orofacial Neurosciences (SCON), Malmö,
Sweden
3
Department of Rehabilitation Medicine, Skåne University Hospital, Lund,
Sweden
4
Danish Headache Center, Department of Neurology, Rigshospitalet-
Glostrup, Faculty of Health and Medical Sciences, University of
Copenhagen, Copenhagen, Denmark
Corresponding author:
Thomas List, Department of Orofacial Pain and Jaw Function, Faculty of
Odontology, Malmö University, SE-205 06 Malmö, Sweden.
Email: Thomas.list@mah.se
List and Jensen
diagnosis and treatment of orofacial pain and TMD is
high, with conservative estimates of around $100 billion
a year in the US alone (5).
Definition
There are several diagnostic systems for orofacial pain/
TMD (2,3,6–8).
The recently published Diagnostic Criteria for TMD
(DC/TMD) is the revised version of the RDC/TMD,
and its development is well-described in the literature
(9). The DC/TMD is based on extensive multicenter
clinical studies  including studies funded by the
National Institutes of Health in the US  and on inter-
national consensus conferences (2). The DC/TMD
comprises two domains, a physical Axis I (diagnosis)
and a psychosocial Axis II (psychosocial assessment;
Tables 1–3).
The strength of the DC/TMD Axis I protocol
includes its reliable and valid diagnostic criteria for
common pain-related disorders and intra-articular dis-
orders (Table 2). The Axis I protocol provides standar-
dized evaluation of subjective symptoms, contains
clearly defined examination methods, and utilizes
specific diagnostic criteria to interpret the clinical find-
ings (Table 1). The Axis II protocol, a psychosocial
assessment, has two options: A brief assessment and a
comprehensive set of instruments for expanded assess-
ment (Table 3). The American Academy of Orofacial
Pain (AAOP) has now incorporated the DC/TMD in
its Guidelines, as has the WHO in the International
Classification of Diseases (ICD-11), classification of
pain (6,10).
Clinical examination (Axis I) diagnostics require a
patient history, including questionnaires and a struc-
tured clinical examination. A questionnaire, together
with these clinical findings, provides enough informa-
tion to diagnose the most common TMD conditions.
Ascertaining that the pain experienced in the clinical
examination is familiar to the patient has proved to
be very important for excluding irrelevant pain.
Likewise, the questionnaire’s timeframe ‘‘in the last
30 days’’ emphasizes a more clinically relevant pain
that is both important to the individual and a reason
why the patient is seeking care. Including these con-
cepts in the provocation of pain – for example, through
jaw movements and palpation – provides criteria to
minimize false-positive findings.
Clinical assessments evaluate pain localization, jaw
movement limitations (lateral, protruding, and mouth
opening), movement pain, TMJ noises, and pain upon
palpation of the masticatory muscles and TMJ.
Written, illustrated instructions for the examination
and an instructional video are available at http://
www.rdc-tmdinternational.org.
693
Chronic pain affects cognitive, emotional, sensory,
and behavioral reactions. These can, in turn, aggravate
and maintain pain. Thus, it is important to assess the
psychosocial situation of patients experiencing chronic
pain and consider it during treatment planning and
prognosis evaluation. The DC/TMD Axis II assessment
of the patient’s psychosocial situation and pain conse-
quences are based on validated instruments (question-
naires) and interpretation guidelines. It includes
instruments for assessing pain behavior, jaw function,
and psychosocial functioning and distress (2). Table 3
shows the instruments recommended for the general
practitioner (brief), and for the orofacial pain specialist
(comprehensive). Studies suggest that use of these
instruments in treatment planning and prognosis
assessment may benefit patients (11,12).
DC/TMD diagnosis: Table 1 presents criteria for
diagnosing three subgroups of TMD-pain.
Muscle pain: Myalgia is the most common TMD
diagnosis and occurs in about 80% of patients with
TMD (13,14). During provocation, patients must also
indicate that they recognize the pain, that the pain is
familiar to them. Myofascial pain with referral is
defined as myalgia plus referred pain beyond the
boundary of the masticatory muscles being palpated,
such as in the ear, teeth, or eye.
Joint pain: Arthralgia often occurs together with a
diagnosis of myalgia; only in rare cases (about 2%) is
arthralgia the only diagnosis (14).
Headache attributed to TMD: Headache attributed
to TMD is headache that occurs in the temple region
secondary to a pain-related TMD, and that is affected
by jaw movement, jaw function, or parafunction. The
headache should be reproducible upon provocation
of the masticatory system. A prerequisite for this diag-
nosis is eliminating other possible headache diagnoses.
Sensitivity and specificity are high for this diagnosis
(Table 2), which simplifies communication between den-
tists, neurologists, and headache specialists. The primary
utility of this diagnosis, in contrast to a primary diagno-
sis (commonly tension-type headache, migraine without
aura, or both), is that it indicates TMD treatment as
the therapeutic approach.
Joint disorders: Disc displacement is a biomechanical
disorder involving the condyle-disc complex. Clinical
studies report its prevalence at 10% for healthy adoles-
cents and around 30% for healthy adults, while in clin-
ical patients approximately 20% of adolescents and
40% of adults have disc displacement with reduction
(13,15,16). For the majority of individuals who experi-
ence joint sounds, the sounds are harmless as long as
there is no pain or functional limitation due to a catch
in jaw movement. The sensitivity and specificity of a
diagnosis of disc displacement without reduction and
with limited mouth opening are good, while they are
694 Cephalalgia 37(7)

Table 1. Diagnostic criteria for the most common pain-related temporomandibular disorders.

Myalgia (ICD-9 729.1; ICD-10 M79.1)*

Decription Pain of muscle origin that is affected by jaw movement, function, or parafunction, and replication of
this pain occurs with provocation testing of the masticatory muscles.
Criteria History Positive for both of the following:
1. Pain**in the jaw, temple, in the ear, or in front of ear; AND
2. Pain modified with jaw movement, function or parafunction.
Exam Positive for both of the following:
1. Confirmationy of pain location(s) in the temporalis or masseter muscle(s); AND
2. Report of familiar painz in the temporalis or masseter muscle(s) with at least one of these
provocation tests:
a. Palpation of the temporalis or masseter muscle(s); OR
b. Maximum unassisted or assisted opening movement(s).
Comments The pain is not better accounted for by another pain diagnosis. Other masticatory muscles may be
examined as dictated by clinical circumstances, but the sensitivity and specificity for this diagnosis
based on these findings have not been established.

Arthralgia (ICD-9 524.62; ICD-10 M26.62)

Decription Pain of joint origin that is affected by jaw movement, function, or parafunction, and replication of
this pain occurs with provocation testing of the TMJ.
Criteria History Positive for both of the following:
1. Pain**in the jaw, temple, in the ear, or in front of ear; AND
2. Pain modified with jaw movement, function or parafunction.
Exam Positive for both of the following:
1. Confirmationy of pain location(s) in the area of the TMJ(s); AND
2. Report of familiar painz in the TMJ with at least one of the following provocation tests:
a. Palpation of the lateral pole or around the lateral pole; OR
b. Maximum unassisted or assisted opening, right or left lateral, or protrusive movement(s).
Comments The headache is not better accounted for by another headache diagnosis.

Headache attributed to TMD (ICD-9 339.89 and 748.0; ICD-10 G44.89)ô

Decription Headache in the temple area secondary to pain-related TMD (see Note) that is affected by jaw
movement, function, or parafunction, and replication of this headache occurs with provocation
testing of the masticatory system.
Criteria History Positive for both of the following:
1. Headache** of any type in the temple; AND
2. Headache, modified with jaw movement, function or parafunction.
Exam Positive for both of the following:
1. Confirmationy of headache in the area of the temporalis muscle(s); AND
2. Report of familiar headachez in the temple area with at least one of the following provocation
tests:
a. Palpation of the temporalis muscle(s); OR
b. Maximum unassisted or assisted opening, right or left lateral, or protrusive movement(s).
Comments The headache is not better accounted for by another headache diagnosis.
Note: A diagnosis of pain-related TMD (e.g. myalgia or TMJ arthralgia) must be present and established using valid diagnostic criteria.
*ICD-9: International Classification of Diseases 9th Revision; ICD-10: International Classification of Diseases 10th Revision
**The time frame for assessing pain including headache is in’’ the last 30 days’’ since the stated sensitivity and specificity of these criteria were
established using this time frame. Although the specific time frame can be dependent on the context in which the pain complaint is being assessed, the
validity of this diagnosis based on different time frames has not been established.
y
The examiner must identify with the patient all anatomical locations where they have experienced pain in the last 30 days. For a given diagnosis, the
location of pain induced by specific provocation test(s) must be in an anatomical structure onsistent with that diagnosis.
z
‘‘Familiar pain’’ or ‘‘familiar headache’’ is based on patient report that the pain induced by specific provocation test(s) has replicated the pain that the
patient has experienced in the time frame of interest, which is usually last 30 days. ‘‘Familiar pain’’ is pain that is similar to or like the patient’s pain
complaint. ‘‘Familiar headache’’ is pain that is similar or like the atient’s headache complaint.
ô
The ICD-9 and ICD-10 have not established a specific code for headache attributed to TMD as a secondary headache; ICD-9 and ICD-10 G44.89 are
for ‘‘other headache syndrome’’ and ICD-9 784.0 is for ‘‘Headache, Facial Pain, Pain in Head’’.
Reproduced with permission from Schiffman et al. 2014 (2).
List and Jensen 695

Table 2. Validity statistics of the DC/TMD by diagnosis. clinical diagnosis of DJD. Computed tomography
(CT) scans of the TMJ may confirm the clinical diag-
DC/TMD
nosis (17).
Diagnosis Sensitivity Specificity

Myalgia 0.90 0.99 Historical background

Myofascial pain with referral 0.86 0.98 The first report of TMD was by a British surgeon in
Headache attributed to TMD 0.89 0.87 1887, who published an article describing surgical man-
Arthralgia 0.89 0.98 agement of disc displacements in the TMJ. An early
Disk displacement and influential publication by Costen emphasized that
With reduction 0.34 0.92 dental malocclusions caused pain around the ear and
With reduction, with intermittent 0.38 0.98 the TMJs, but also related to other ear symptoms such
locking as tinnitus, impaired hearing, and dizziness. In the dec-
Without reduction, with limitation 0.80 0.97 ades following this, TMD research focused on single-
Without reduction, without limitation 0.54 0.79 factor explanations of TMD – such as the TMJ, muscle,
Degenerative joint disease 0.55 0.61 or dental occlusion – but found little supporting evi-
Subluxation 0.98 1.00
dence (9).
More recent research recognizes that TMD is not
Reproduced with permission from Schiffman et al. 2014 (2). caused by a single factor but is a complex disorder
with overlapping comorbidities of physical signs and
symptoms, as well as changes in behaviors, emotional
Table 3. Recommended Axis II assessment protocol for the status, and social interactions as manifestations of gen-
DC/TMD. eral central nervous system dysregulation (18). This has
led to acceptance of a multifactorial etiology and the
Domain Instrument Brief Comprehensive
widespread use of the biopsychosocial model of TMD
Pain location Pain drawing ˇ ˇ pain (3). The RDC/TMD was the first classification
Physical Graded chronic pain ˇ ˇ that incorporated the biopsychosocial pain model,
function scale, GCPS and it has been translated into 22 languages and has
Limitation Jaw function limitation ˇ ˇ an overwhelming number of literature citations (9).
scale, JFLS-8
JFLS-20
Distress Patient health ques- ˇ
Symptomatology
tionnaire, PHQ-4 The signs and symptoms associated with TMDs vary in
Depression Patient health ques- ˇ their presentation and will often involve more than one
tionnaire, PHQ-9 component of the masticatory system. The three major
Anxiety Generalized anxiety ˇ signs and symptoms are pain, limited range of motion,
disorder, GAD-7 and TMJ sounds. Pain is usually the main complaint,
Physical Patient health ques- ˇ originating in the temporal area and the cheek, but also
symptoms tionnaire, PHQ-15 affecting the peri-auricular area. This pain is aggravated
Parafunctions Oral Behaviors ˇ ˇ by provocation, such as chewing, yawning, or talking.
Checklist, OBC The pain can be intermittent or persistent and is of mod-
Reproduced with permission from Schiffman et al. 2014 (2).
erate intensity, on average, but there are cases with
severe pain intensity. Pain and tenderness upon palpa-
tion of the pericranial muscles and TMJ are the most
common clinical signs and they do often coexist (14).
poor for disc displacement without reduction and with- Other symptoms also reported include i) comorbid
out limited mouth opening. For a definitive diagnosis, pain conditions such as tension-type headache (TTH),
MRI is required (2). ii) neck and back pain, and iii) psychosocial distress,
Joint diseases: Arthrosis/osteoarthrosis is a degen- such as depression and anxiety (19).
erative joint disease (DJD) characterized by loss of
cartilage and bone with concurrent remodeling of
Epidemiology
underlying bone tissue. Diagnostic criteria include
patient reports of crepitation from the TMJ during Reports indicate the prevalence of TMD in the popu-
jaw movements and clinical findings that confirm this. lation to be about 10–15% for adults and 4–7% for
Sensitivity and specificity are reasonably high for the adolescents (20–22). Incidence reports for adults
696
meeting a TMD-pain diagnosis were 3.9% and for self-
reported TMD-pain in adolescents, 4.6% (23,24). The
condition affects women more frequently than men and
is most common in the child-bearing years (20–40
years), with a decrease in distribution with age (20).
In adults, the sex ratio is approximately 2:1
(women:men) in population-based studies and 4:1 or
more among clinical cases of TMD pain (1). There
are no gender differences in children, but with increas-
ing age during adolescence to young adulthood, the sex
ratio increases to approximately 2:1 (girls:boys) (21,25).
In a longitudinal study in adults, 49% of the incident
cases reported persistent pain when re-examined six
months later (26). Similarly, in a longitudinal study of
adolescents, 45% reported TMD pain once a week or
more when re-examined 10–12 years later (27).
Risk factors
The etiology of TMD-pain is considered multifactorial,
and several risk factors appear to predispose, precipi-
tate, or prolong TMD-pain (22). These can include bio-
logical factors (e.g., sex hormones), endogenous opioid
function, differences in anatomical genotypes, trauma,
occlusal changes, parafunctions, and psychosocial
factors (e.g., stress exposure, pain coping, stress, cata-
strophizing, and emotions). Maixner et al. proposed a
model for how risk factors interact and contribute to
the onset of TMD pain (28). An extensive National
Institute of Dental and Craniofacial Research
(NIDCR)-funded prospective study (the Orofacial Pain
Prospective Evaluation and Risk Assessment, OPPERA)
investigated several of these factors, assessing genetic
and phenotypic measures of biological, psychosocial,
clinical, and health-status characteristics (28). A decade
later, many of these risk factors have been confirmed,
but there are also new findings regarding risk factors,
which we discuss in the following text (26).
Genetics
The case-control component of the OPPERA study
explored genetic risk factors for TMD pain. It assessed
over 350 candidate pain genes using a candidate gene
panel. The study indicated an association between
TMD and two genes: HTR2A and COMT (29).
Smith et al. proposed the biological pathways through
which genetic variations could causally interact to influ-
ence development of TMD pain (30). A systematic
review supported these findings, showing evidence for
an association between TMD pain and genes. However,
the genes involved seem to account only for small asso-
ciations with TMD pain, and they interact with other
genes and environmental influences (31). The main con-
tribution seems to be from candidate genes that encode
Cephalalgia 37(7)
proteins involved in the processing of painful stimuli
from the serotonergic and catecholaminergic systems
(31).
Hormonal factors
Since TMD pain is more frequent in females, some have
suggested that female sex hormones, such as estrogen,
are involved in pain modulation (32). Estrogen seems to
be involved in modulating TMJ inflammation and reg-
ulating nociceptive responses in both the peripheral and
central nervous systems (33). LeResche et al. reported
that the periods of highest TMD-pain may be corre-
lated with rapid periods of change in estrogen levels,
whereas other studies have found a correlation between
low estrogen levels and TMD pain (32). Overall, how-
ever, a systematic review found the evidence supporting
the hypothesis that estrogen levels are associated with
TMD to be weak (34).
Pain comorbidity
In one large population-based cross-sectional study,
83% of subjects suffering from TMD pain reported
one comorbid pain condition and 59% reported at
least two (35). The most commonly reported comorbid
painful conditions in persons with TMD-pain are head-
ache, neck pain, and back pain (36).
In cases with TMD pain, the majority of adults and
adolescents report headache [21,37,38]. Subjects with
TMD-pain were up to 8.8 times more likely to have
headache compared to individuals without TMD-pain
(38), and in most cases, the headache could be charac-
terized as TTH. Likewise, headache seems to precede
TMD pain in many adolescents with pain (39).
A case-control study found that adults with
headache at least once a week had an increased risk
of orofacial pain (OR ¼ 3.7) (40). A cohort study for
adolescents found that, for those with headache, the
chance of developing TMD pain was 2.7 times higher
than for adolescents without headaches (25). Another
study found that adults who frequently experienced
headache were more likely to present with aggravated
TMD signs and symptoms than individuals with a
lower headache frequency (41).
Adults and adolescents with TMD commonly report
neck and back pain (39,42). Studies showed that sub-
jects with TMD pain are 2.6–5 times more likely to
have low-back pain compared to individuals without
TMD pain (39,42).
Widespread pain is common among persons with
TMD pain (43, 44). Most patients with Fibromyalgia
Syndrome (FMS) seem to exhibit TMD pain (45). The
OPPERA study also confirmed that comorbid pain
conditions were an important predictor for onset of
List and Jensen
TMD pain (26). More information regarding painful
and non-painful comorbidities in orofacial pain
appears in Velly et al. 2014 (19).
Trauma and parafunctions
Trauma, both macro- and microtrauma, is another pos-
sible cause of TMD pain (22). Macrotrauma may occur
following injuries or after prolonged mouth opening,
such as during dental treatment or intubation. The
OPPERA study found that trauma after prolonged
mouth opening may predict onset of TMD-pain (46),
but the cause-effect relationship here is still unclear.
Microtrauma may occur after parafunctional habits
such as bruxism (tooth clenching and or grinding), bra-
cing the jaw, tongue thrusting, fingernail biting, or
pencil/pen chewing. Bruxism has two distinct circadian
manifestations: It can occur during sleep (sleep brux-
ism) or during wakefulness (awake bruxism) (47).
Lobbezoo et al. proposed a grading system that
defines possible, probable, and definite sleep and
awake bruxism (47). A large population-based cross-
sectional survey found that more than 8% of respond-
ents self-reported sleep bruxism at least weekly, while
another study using objective measures (electromyog-
raphy, EMG) reported a prevalence of 7% (48,49). A
systematic review concluded that when self-reported
bruxism determined the diagnosis of bruxism there
was a positive association with TMD pain, but when
stricter diagnostic criteria for bruxism were used, the
association with TMD symptoms was much lower
(50). The OPPERA study found that self-report of par-
afunction was a strong predictor of the onset of TMD
(26). However, findings on the strength of the associ-
ation between awake bruxism, sleep bruxism, and
TMDs are inconsistent (50).
Occlusal factors
The relationship between dental occlusion and TMD
has been a controversial topic in the dental community.
A systematic review of population-based studies found
only few and inconsistent associations between mal-
occlusions and TMD symptoms (51). A large epidemio-
logical cross-sectional survey of adults found similar
results, with detected associations between malocclu-
sions and clinical signs of TMD also being few and
inconsistent, with no associations with functional
occlusion factors (52).
Orthodontic treatment alters occlusion, which sug-
gested considering it a risk factor for developing TMD
(53,54). But a systematic review investigating TMD in
relation to orthodontic treatment concluded that there
was no support for the belief that orthodontic treat-
ment may cause TMD (55). Similar results appeared
697
in a longitudinal study investigating the relationship
between orthodontic treatment and TMD, which
found that orthodontic treatment neither causes nor
prevents TMD (56).
Psychosocial
Individuals with TMD-related pain show higher
levels of stress, anxiety, depression, somatic awareness,
pain catastrophizing, and kinesiophobia compared
with controls [40, 57–61]. A case-control study demon-
strated that patients with TMD-pain were more likely
to have higher levels of anxiety (OR ¼ 5.1), soma-
tization (OR ¼ 2.7), and depression (OR ¼ 3.5) than
controls [40].
One three-year cohort study demonstrated that
depression (incidence density ratio [IDR] ¼ 3.2), per-
ceived stress (IDR ¼ 2.6), and mood (IDR ¼ 3.7)
increased the risk of TMD [62]. Another three-year
cohort study showed that adolescents who experienced
somatization (OR ¼ 1.8,) and life dissatisfaction
(OR ¼ 4.1) had an increased risk of TMD-pain, regard-
less of gender and the presence of other pain complaints
[25]. Studies have also demonstrated that psychological
comorbidities contribute to the persistence of TMD-
pain, regardless of the presence of painful comorbid-
ities. For example, in another cohort study, depression
and catastrophizing contributed to the onset and per-
sistence of dysfunctional TMD-pain [44, 63].
In summary, several psychosocial factors can predis-
pose a person to TMD-pain, precipitate it, or prolong
it (25). The OPPERA study found several psychological
variables to predict onset of TMD pain, but the most
strongly associated were perceived stress, previous
stressful life events, and negative affect at a three-year
follow-up (64). In the individual, however, the inter-
action of factors may play a more significant role
than one factor alone. Svensson and Kumar have pro-
posed a stochastic model to better understand this
interplay between risk factors and the development of
TMD pain (65).
Pathophysiology
The exact pathophysiology of TMD is not yet clear des-
pite multiple experimental studies, but several multifac-
torial models have been suggested [for comprehensive
reviews please see (66–69)). There are relevant clinical
overlaps between TMD and some headache conditions,
especially TTH. Therefore, it is likely they have similar
pathophysiological mechanisms. Peripheral and central
sensitization may be important mechanisms contribut-
ing to the close association and complex relationship
between TMD and TTH, as both disorders occur in
similar anatomical areas and may reflect a possible
698
impairment of descending modulatory pain pathways
and the processes of referred pain. In addition, the
clinical examination does not provide enough informa-
tion to differentiate between TTH and TMD, as myo-
fascial tenderness and pain are prominent symptoms of
both disorders. Due to the similarities in the patho-
physiology and clinical presentation of TTH and myo-
fascial TMD, their comorbidity may arise from a lack
of distinction between the disorders. These overlaps are
also reflected in the current classification systems of
both TMD and headache, and appear in the thera-
peutic strategies used to manage myofascial TMD
and TTH.
The origin of pain in TMD has traditionally been
attributed to increased contraction and ischemia of the
masticatory muscles. However, numerous laboratory-
based EMG studies have reported normal or only
slightly increased muscle activity, while it seems that
ischemia alone cannot induce TMD pain but can only
provoke stronger TMD pain in combination with
prolonged contraction and repetitive muscle work.
Many human studies have consistently shown that the
pericranial myofascial tissues are considerably more
tender in patients with TMD than in healthy subjects,
and that this tenderness positively associates with both
the intensity and the frequency of TMD, just as in TTH
(70–74). Moreover, infusion of hypertonic saline into
the masseter muscles in healthy subjects elicits a pain
that is perceived as TMD pain (75), and several studies
report an increased number of active trigger points
in the pericranial muscles of patients with TMD (73),
supporting the presence of an important muscular com-
ponent in TMD pain.
While theory originally attributed increased myofas-
cial pain sensitivity to release of inflammatory
mediators, resulting in excitement and sensitization of
peripheral sensory afferents, animal and human experi-
mental models have challenged this hypothesis, as only
injections of Nerve Growth Factor (NGF) and hyper-
tonic saline can provoke pain by themselves. Otherwise,
various combinations of algesic substances, such as
bradykinin, serotonin, glutamate, or calcitonin gene-
related peptide (CGRP), are necessary to elicit clinically
relevant pain. Concomitant psychophysical measures
indicate that peripheral sensitization of myofascial
sensory afferents was responsible for hypersensitivity.
Nevertheless, it also seems that a clinically relevant
TMD model must include several other factors. The
issue of gender is also highly relevant due to the
female preponderance in TMD cases. A Spanish
study of 20 female patients with TMD and 20 healthy
controls noted the presence of bilateral and widespread
pressure-pain hypersensitivity in women with myofas-
cial TMD, suggesting that widespread central sensitiza-
tion is involved in myofascial TMD. This finding also
Cephalalgia 37(7)
has implications for the development of management
strategies (76).
A recent German study demonstrated that sleep-
associated disturbances increased muscle activity as
measured by EMG, and facial pain in the morning
occurred in 71% of patients with TMD compared to
13.6% in healthy controls (77). In fact, the OPPERA
study found that deteriorating sleep quality predicted
TMD incidence (26). Research has sought reliable diag-
nostic biomarkers for TMD, and interestingly, recent
studies report dopamine to be markedly elevated in
plasma from TMD patients (77,78), with a close correl-
ation to pain intensity and perceived stress.
Like TTH, TMDs generally seem to occur in relation
to emotional conflict and psychosocial stress, but the
cause-effect relationship is not clear. As in other
chronic pain disorders, psychological abnormalities in
TMD can be viewed as secondary rather than primary,
and depression and maladaptive coping strategies (e.g.,
catastrophizing and avoidance) are also secondary to
the pain. In addition, depression may aggravate an
existing central sensitization in both TMD and frequent
headaches. Thus, there may be a bidirectional relation-
ship between depression and TMD.
Maixner et al. have proposed a model that aims to
include risk factors for the onset and persistence of
TMD (28), illustrated in Figure 1.
To summarize, pericranial myofascial pain sensitiv-
ity is higher in patients with TMD. Peripheral mechan-
isms most likely play a role in the onset of TMD,
whereas more central factors such as sensitization of
second-order neurons at the level of the spinal dorsal
horn/trigeminal nucleus and supraspinal neurons,
imbalanced antinociceptive activity, as well as genetic
predisposition, drive the persistence of pain (Figure 1).
Longitudinal studies will be necessary to provide final
evidence for the cause-effect relationship between TMD
and central sensitization.
Treatment
The treatment need for TMD in the general adult popu-
lation is substantial and varies according to definition,
criteria, and age. Some authors suggest that the treat-
ment need is approximately 15% of the population
(79), whereas available data indicate that only a minor-
ity of patients with TMD pain receives treatment (21).
There is no single approach for treating patients with
TMD. The following discusses some of the more
common treatment approaches.
Reports show behavioral therapies to be effective
in treating TMD (80). These therapies include counsel-
ling, education, biofeedback, cognitive behavioral
therapy (CBT), habit reversal, self-treatment at home
after instruction, and relaxation techniques (81,82).
List and Jensen 699

Persistent TMD

Painful First-onset TMD

ENVIRONMENTAL
TMD
CONTRIBUTIONS
Subclinical signs & symptoms
Physical environment
eg. trauma, infection

Social environment
eg. life stressors
High
Culture High State of Pain
eg. health Psychological
Amplification
beliefs Distress
Demographics

Mood Neuro-
endocrine Impaired Pro-
Stress pain inflammatory
Anxiety finction
response Autonomic regulation state
Somatization finction
Depression

GAD65 Cannablnold Dopamine Serotonnin Na+, K+-

receptors transporter CACNA1A NET ATPase IKK COMT
Serotonin receptors Opioid
MAO Adrenergic
receptor NMDA GR DREAM POMC receptors BDNF NGF Prodynorphin Interleukins
CREB1 receptors

Xp11.23 12q11.2 9q34.3 11q23 5q31-q32 5q31-32 6q24-q25 1p13.1 22q11.21

Figure 1. Risk factors that contribute to the onset and persistence of TMD.
This model displays two principal intermediate phenotypes (psychological distress and pain amplification) that contribute to the onset
and persistence of temporomandibular disorder (TMD). Each intermediate phenotype represents a constellation of more specific risk
factors, all of which are subject to genetic regulation. Interactions between these intermediate phenotypes occur in the presence of
environmental factors that further contribute to the onset and persistence of painful TMD. The model does not show time, because
its effects occur implicitly in a third dimension that is not readily shown in the diagram. Reproduced with the permission of Maixner
et al. (28).

Systematic reviews have indicated low to moderate evi-
dence for treatment effects, depending on which studies
the review evaluated (80,82). Behavioral therapies are
often an essential part of self-management programs,
and the Swedish national guidelines suggest their use as
a first-line therapy for TMD (83). However, further
controlled trials are necessary to determine the effect-
iveness of these programs.
Therapeutic jaw exercises can provide coordination
training, relaxation, and strengthening of the muscles.
Passive stretching may improve muscle mobility and
range of movement of the TMJ and, in addition, may
also help patients overcome fear of moving their jaws.
Jaw exercises are often part of self-care programs for
patients with TMD pain (81). Evidence suggests low to
moderate effects for these treatments, but more rigor-
ously designed clinical trials are necessary (84,85).
Sensory stimulation treatment (e.g., transcutaneous
electrical nerve stimulation (TENS) and acupuncture)
aims to activate the afferent nervous system and
thereby modulate endogenous pain control systems
to promote pain relief. Acupuncture demonstrated
superior pain relief in TMD and myalgia compared
with no treatment, and efficacy equal to other therapies.
However, compared with a placebo, results are contra-
dictory (86). No evidence supports TENS or low-level
laser in the treatment of TMD pain (82).
Occlusal appliance therapy is one of the most
commonly used treatments for TMD pain, with stabil-
ization appliances being the type most often recom-
mended. The treatment is reversible, atraumatic, and
may induce relaxation of the jaw muscles, unload the
TMJ, and protect the teeth from wear due to bruxism.
But the mechanisms of action have not been well stu-
died. Studies show that wearing an occlusal appliance
while asleep is likely to lead to short-term improve-
ment, but the outcome is inconclusive compared with
a placebo (non-occluding palatinal splints). Overall,
700
there is good evidence for modest efficacy of various
oral appliances in the treatment of TMD-pain (87).
Patients with headache attributed to TMD reported
that headache frequency and intensity decreased after
treatment with stabilization appliances, but that the
effect was similar to other interventions (88,89).
Studies found no evidence that occlusal adjustments
(grinding on teeth) are more or less effective than a
placebo in the treatment of TMD pain. All studies
were restrictive in recommending the use of occlusal
adjustments for treatment of TMD pain, especially
since this therapy is non-reversible (90).
Systematic reviews found that non-steroidal anti-
inflammatory drugs (NSAIDs), acetaminophen, diaze-
pam, hyaluronate, glucocorticoid, tricyclic antidepressants
(TCAs), and antiepileptic drugs may be effective in treat-
ing TMD pain. But few primary studies were well
designed with a relevant follow-up time, so results were
heterogeneous and no firm conclusions can be drawn
(82,91). Because of current limitations in the knowledge
of pharmacologic effects on TMD pain, it is only pos-
sible to make comparisons between similar pain condi-
tions such as backache or TTH. In several chronic pain
conditions, acute drugs (e.g., analgesics and opioids)
and preventive drugs (e.g., antidepressants and anti-
epileptics) seem effective in relieving pain (92); thus,
these drugs would probably be effective for TMD pain.
A recent study tested a stepped pharmacotherapeutic
protocol and demonstrated a good response in persist-
ent myofascial pain, even in more severe cases. Patients
who did not respond to TCAs may represent a distinct
subgroup for whom gabapentin, at a lower dose than
previously reported, may be a good alternative (93).
Preventive drugs are always preferable for persistent
TMD pain, as the benefits of acute drugs must be
weighed against possible adverse and toxic effects and
the risk of dependency. The potential risk of medication
overuse is particularly significant for headache, as these
patients have a very high incidence of comorbid pri-
mary headaches, so it is important to limit the use of
all types of acute analgesics to a short period of time
and to a maximum of two to three days a week.
A systematic review of surgical treatment of the
TMJ concluded that arthroscopic surgery, arthrocent-
esis, and physical therapy all had similar effects on
reduction of mandibular pain intensity and functioning
(82,94). Success rates were often high, independent of
Article highlights
. Chronic TMD is a complex musculoskeletal disorder with multifactorial etiology.
. A biopsychosocial illness model is recommended in the diagnosis and treatment of TMD pain.
Cephalalgia 37(7)
treatment mode, but long-term follow-up studies are
lacking. Many of the RCTs included in the systematic
reviews had low quality scores and outcome measures
were often coarse, which made data difficult to inter-
pret. A majority of patients with painful disc displace-
ments have been found to respond favorably to
conservative treatment modalities. Therefore, surgical
TMJ approaches are only appropriate in select patients
who have been refractory to conservative treatment for
at least six months and suffer from severe disability
related to conditions in the TMJ (83).
Expert opinion: Open questions and burning desires:
. Clarify the clinical and pathophysiological overlap
with myofascial pain and TTH.
. Produce a uniform set of diagnostic criteria for
TMD to be used by all professionals.
. Are there sensitive and specific diagnostic markers
for TMD?
. What are effective treatment strategies to prevent
chronification?
Expert opinion: Future paths:
. Develop and implement aligned diagnostic criteria
for TMD and headache.
. Develop and implement aligned diagnostic instru-
ments for Axis 1 and 2 for both TMD and headache.
. Tailor and test better treatment strategies for TMD
and headache.
. Adopt a multidisciplinary approach with a team of
orofacial pain specialists and a neurologist (head-
ache specialist) for the most precise differential diag-
nosis possible and initiation of the best and most
efficient multimodal treatment.
. Build closer collaborations between animal and
human experimental pain models.
Conclusions
Chronic TMD is a complex musculoskeletal disorder
with multifactorial etiology. Physical, behavioral and
emotional factors overlap and interact in TMD.
Therefore, an approach based upon a biopsychosocial
illness model is recommended in the diagnosis and
treatment of TMD pain.
List and Jensen
Author contributions
Both authors contributed to the analysis, draft, and revision
of the manuscript.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The authors received no financial support for the research,
authorship, and/or publication of this article.
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