DR.

GALIT ALMOZNINO (Orcid ID : 0000-0001-9671-0047)

Accepted Article
Article type : Original Article

Muscle Tenderness Score in Temporomandibular Disorders Patients:

A Case-Control Study

Galit Almoznino DMD, MSc, MHA 1,2*; Avraham Zini DMD, Ph.D., MPH3; Avraham

Zakuto DMD4; Hulio Zlutzky DMD5; Stav Bekker DMD5; Boaz Shay DMD, PhD6,Yaron

Haviv DMD, PhD7; Yair Sharav DMD, MS8; Rafael Benoliel, BDS, LDS, RCS9

1
Lecturer, Director, Orofacial Sensory Clinic, Department of Oral Medicine, Sedation &
Maxillofacial Imaging, Hebrew University-Hadassah School of Dental Medicine, Jerusalem,
Israel;
2
Head, division of big data Research, Department of Community Dentistry, Hebrew
University-Hadassah School of Dental Medicine, Jerusalem, Israel;
3
Professor, Associate Dean; Head, Department of Community Dentistry, Hebrew University-
Hadassah School of Dental Medicine, Jerusalem, Israel;
4
Clinical Director, Temporomandibular Joint Disorders Clinic, Department of
Prosthodontics, Oral and Maxillofacial center, Israel Defense Forces, Medical Corps, Tel-
Hashomer, Israel;
5
Senior physician, Temporomandibular Joint Disorders Clinic, Department of Prosthodontics,
Oral and Maxillofacial center, Israel Defense Forces, Medical Corps, Tel-Hashomer, Israel
6
Clinic Manager, Head of Research, Endodontic Department, Faculty of Dental Medicine,
Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel;
7
Lecturer, Director, Orofacial Pain Clinic ,Department of Oral Medicine, Sedation &
Maxillofacial Imaging, Hebrew University-Hadassah School of Dental Medicine, Jerusalem,
Israel;
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/joor.12743

This article is protected by copyright. All rights reserved.

 8
Professor Emeritus, Department of Oral Medicine, Sedation & Maxillofacial Imaging,
Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel;
Accepted Article
9
Professor, Associate Dean for Research; Director, Center for Orofacial Pain and
Temporomandibular Disorders, Rutgers School of Dental Medicine, Rutgers, The State
University of New Jersey, Newark, New Jersey, USA

*Corresponding author:

Dr. Galit Almoznino DMD, MSc, MHA

Director, Orofacial Sensory Clinic,
Department of Oral Medicine, Sedation & Maxillofacial Imaging,
The Hebrew University-Hadassah School of Dental Medicine
P.O. Box 12272
Jerusalem 91120, Israel
Tel: 972-2-677-6140; Fax: 972-2-644-7919
[email protected]

Short title: Muscle tenderness scores in TMD patients

The authors deny any conflicts of interest.

The authors declare self-funding of the research.

Abstract
Background: The total tenderness score is commonly used in headache practice and

contributes valuable information.

Objective: To assess muscle tenderness scores in patients diagnosed with

Temporomandibular disorders (TMD) and analyze their associations with various

demographic and clinical parameters.

This article is protected by copyright. All rights reserved.

 Methods: Masticatory (MTS), cervical (CTS) and total (TTS) tenderness scores were

analyzed in this case-control study among 192 TMD patients and 99 controls. The study
Accepted Article
included a questionnaire and a clinical examination following RDC/TMD guidelines. Data

were analyzed using: Pearson’s Chi-Square, analysis of variance, t-test and Bonferroni post-

hocs. To examine the factors associated with MTS score in a multivariate manner, a

conceptual hierarchical multiple regression model was adopted.

Results: MTS and TTS differed between TMD sub-groups and controls. Muscle tenderness

was positively associated with: female sex, whiplash history, parafunction, co-morbid pains

such as headaches and body pain, pain intensity, onset, frequency, and duration. In the

conceptual hierarchical multiple regression model, pain onset, frequency ,and duration, co-

morbid pains were mediators in the relationship between TMD diagnosis and MTS.

Conclusion: Muscle tenderness scores were positively associated with TMD disease

characteristics and comorbid pain conditions, which may reflect associations with disease

severity. MTS differed between TMD populations and may be used in routine patient work-

up, to assess MMD severity and changes over time as well as treatments response and as a

research tool. MTS can be used as a common methodology to describe both headaches and

masticatory muscle disorders and to facilitate interprofessional research and crosstalk

between a headache and orofacial pain practitioners.

Key Words: Orofacial pain, Temporomandibular disorders, Masticatory muscle disorders,

muscle tenderness score.

This article is protected by copyright. All rights reserved.

 Abbreviations used:

IHS: International Headache Society

Accepted Article
TMD: patients with Temporomandibular disorders (i.e MMD,TMJ and TMP)

DC/TMD: Diagnostic Criteria for Temporomandibular Disorders

RDC/TMD: Research Diagnostic Criteria for Temporomandibular Disorders

MMD: patients with Masticatory muscle disorders

TMJD: patients with Temporomandibular joint disorders

TMP: patients with both MMD and TMJ

VPS: Verbal pain scale

TTS: Total tenderness score

MTS: Masticatory muscles tenderness score

CTS: Cervical muscles tenderness score

Background

The significance of muscle tenderness in painful masticatory muscle disorders (MMD) and

tension type headache (TTH) has long been of interest. Pericranial myofascial tissues are

considerably more tender in patients with MMD and headaches such as TTH than in controls,

and increased pericranial tenderness is recognized as the most significant abnormal finding 1-
4
.

MMD are categorized under the "umbrella" term Temporomandibular disorders (TMD), a

group of musculoskeletal disorders that involve the temporomandibular joint (TMJ), the

masticatory muscles or both 4. TMD represent the most common chronic orofacial pain

This article is protected by copyright. All rights reserved.

 disorder, harming 5-12% of the population 4,5.TMDs may severely impact daily life, social

and psychological status of patients and their quality of life 4,6,7.

Accepted Article
For diagnosis, the Research Diagnostic Criteria for TMD (RDC-TMD) require the presence

of at least 3 tender muscle sites out of 20 sites 8. Its revised form (DC ⁄TMD) requires the

confirmation of pain locations in the temporalis or masseter muscles only 4, because these

sites have the highest specificity and sensitivity. The DC ⁄TMD states that other masticatory

muscles may be examined but their diagnostic sensitivity and specificity have not been

established 4.

Nevertheless, the current DC/TMD classification does not determine MMD severity,

changes over time, or response to treatment. The ability to determine MMD severity may

change the way we approach patient management by enabling different treatment protocols
9
according to TMD severity, such has been done for many chronic diseases such as asthma .

Moreover, the clinician will be able to assess changes in TMD severity over time, explain the

concept of severity to the patient, assess treatment response in different TMD severity levels

and assess TMD severity during research. This led to the question posed by Benoliel and

Sharav of what is clinically more important regarding disease severity: how many muscles

are involved or how tender they are? 10.

The muscle tenderness score 11-16, is commonly used in headache practice for the assessment

of the severity of pericranial muscle tenderness and contributes valuable information beyond

the number of muscles involved 3,12,17. For example, increased levels of pericranial muscle

tenderness evaluated by manual palpation have been demonstrated in chronic tension-type

headache patients compared to headache-free controls18-20and migraineurs on the

symptomatic side14. In migraine patients, pressure pain thresholds levels and muscle

tenderness scores were negatively correlated 14 . In fact, according to the International

Headache Society (IHS), increased pericranial tenderness is the most significant abnormal

This article is protected by copyright. All rights reserved.

 finding in patients, with any type of Tension-type headache21. In masticatory muscle

disorders patients the tenderness score was found to correlate to the pain scores better than
Accepted Article
the number of involved muscles and may add further information beyond the number of

involved muscles 10.

Painful disk displacement also correlated with ipsilateral muscle tenderness22,and

high levels of muscle tenderness correlated with high levels of jaw and neck dysfunction23.

There is some overlap between "headache attributed to TMD" and "TTH with pericranial

tenderness"1. Therefore, the establishment of a method describing both entities in terms of

muscle tenderness scores and pain characteristics is useful. This will facilitate communication

between headache and orofacial pain practitioners and researchers.

Our primary objective was to assess the total muscle tenderness score (TTS) in the diagnosis

of TMD.

Specific objectives of this study were to:

1. Measure the masticatory and total muscle tenderness scores as well as the number of

involved muscles in patients with TMD compared to TMD-free controls and across

TMD sub-groups.

2. Analyze the associations between various demographic and clinical parameters and the

muscle tenderness scores.

We hypothesized that the muscle tenderness scores are positively associated with disease-

related outcomes and co-morbid pain conditions. To lessen confounders like aging and

illnesses we only included young subjects without co-existing mental, psychiatric or physical

impairments which improved our ability to evaluate the impacts of other demographic and

clinical parameters on muscle tenderness scores. Thus, the study was limited to patients who

developed TMD as children or teenagers or in early adulthood.

This article is protected by copyright. All rights reserved.

 Methods

Study groups
Accepted Article
This is part of a series of papers focusing on the demographic, clinical and behavioral aspects

of patients with TMD 6,24. This case-control study was conducted between March 1st, 2011

and January 31st, 2013. Data were collected from consecutive individuals referred to the

TMD Clinic (a secondary referral center) at the Department of Prosthodontics, Tel-

Hashomer, Israel, with a primary complaint of TMD. This department is a secondary

prosthodontics referral center that coordinates the management TMD patients referred by

dentists and physicians from primary clinics all through the country.

Sample size calculation using WINPEPI software25 determined that at least 256 participants

in two groups with 60:40 ratio, was needed to provide 90% statistical power to identify a 2.0-

point difference in TTS, with alpha set at 0.05, and an estimated standard deviation of 4.4 for

the larger group and 5.3 for the smaller group, based on our experience in analyzing muscle

tenderness scores among orofacial pain patients 10.

100 consecutive, fairly similar in age and sex TMD-free individuals attending a routine dental

screening in a primary dental clinic formed the control group.

Ethical approval

The study adheres to STROBE guidelines and met the requirements of the

Tel Hashomer Institutional Review Board (No. 1000-2010). All participants signed an

informed consent form and received free and unconditional treatment.

This article is protected by copyright. All rights reserved.

 Inclusion Criteria and Diagnoses

Inclusion criteria: patients attending for new screenings, aged 18- 30 years.
Accepted Article
Exclusion criteria for both groups were: drug/alcohol/mediactions abuse; Fibromyalgia;

patients with medical and/or dental emergencies; pregnancy or lactation; mental, psychiatric

or physical impairments; co-existing malignant or significant medical conditions; current use

of drugs/medications that effect on central nervous system (e.g.opioids, tricyclic-

antidepressants, anticonvulsants, and/or muscle relaxants).

TMD was diagnosed according to Axis I of the Research Diagnostic Criteria for

Temporomandibular Disorders (RDC/TMD) 8, which was the most accepted diagnostic

instrument at the time the study was performed. TMD patients were divided into three

diagnostic categories: (a) MMD- masticatory muscle disorders: comprised of Group I muscle

disorders ( I.a Myofascial pain ,I.b Myofascial pain with limited opening) (b) TMJD- isolated

disorders of the temporomandibular joint: comprised of Group II (disc displacements: II.a

DD with reduction,II.b DD without reduction with limited opening,II.c DD without reduction

without limited opening) and Group III (Other common Joint disorders: IIIa. arthralgia, IIIb.

osteoarthtitis, IIIc. osteoarthrosis) and (c) TMP - patients with both MMD and TMJ.

Controls, as well as cases, were examined and any of the controls who met the criteria for an

RDC/TMD diagnosis were excluded from the study.

Data collection

The study included a questionnaire and a clinical examination, performed on both TMD

patients and controls, at the first meeting and before treatment. The interviewer administered

the questionnaire during the one-on-one consultation, on a standard form. The questionnaire

included:

(1) personal details: sex (male/female),age in years.

This article is protected by copyright. All rights reserved.

 (2) History of trauma was assessed using the following questions:

a) Have you had a traumatic event to the head and/or neck? (Yes / No) Details
Accepted Article
b) Have you had jaw fractures? Yes / No Details ________

c) Have you had whiplash injury? Yes / No Details ________

(3) co-morbid headache (Migraine, Tension type headache [TTH],none).The diagnosis of

headaches was assessed either from reported medical history or as a result of the patient

being diagnosed at our department as part of the patient evaluation process according to the

International Classification of Headache Disorders, 3rd edition (beta version) 1. In case the

individulal had both types of headaches, the question that was asked to decide what group to

place an individual in was: "what is your most frequent headache".

(4) parafunctional habits were assessed using the following questions:

Oral habits

1. Do you clench your teeth? Yes / No

2. Do you grind your teeth? Yes / No

3. Do you suffer from sleep bruxism? Yes / No

4. Does your partner report that you suffer from sleep bruxism? Yes / No

Pain evaluation

Patients approximated the period since muscle pain began, duration of pain episodes and

frequency, and the presence of co-morbid body pain in other body sites. Current pain

intensity was rated on a 0-10 verbal pain scale (VPS).

Pain on unassisted mouth opening was asessed on a 4-point ordinal scale: 0 (no pain), 1

(mild), 2 (moderate) and 3 (severe)6.

This article is protected by copyright. All rights reserved.

 Clinical Examination

Clinical examination was performed in both TMD patients and control subjects, including
Accepted Article
masticatory and neck muscle tenderness to palpation. Muscle palpation was performed

according to the RDC-TMD guidelines. All examinations were conducted by one of two

senior authors (A. Zakuto and H.S.). Prior to the beginning of the study, a training and

calibration session was performed for the examiners to ensure mutual agreement and correct

interpretation of the measurements used in the study. All diagnoses were confirmed in the

clinic and then re-examined following data tabulation and summary by both senior authors

(R.B., Y.S.).

Muscle insertions were palpated 15. Muscles were palpated bilaterally in the same order for

all patients. Palpation was performed with small rotational movements of the assessor’s

second and third fingers during 4–5 seconds 15. Muscle palpation was performed with about 2

to 3 pounds of palpation pressure 26-28. Tenderness to palpation was scored on a 4-point

ordinal scale: 0 (no pain), 1 (mild), 2 (moderate) and 3 (severe) 11-15,19,29.

Masticatory Muscle Tenderness Score (MTS) was the mean sum of the palpation scores from

the masseter and temporalis muscles. Cervical muscles included the following muscles:

suboccipital group (as one), sternocleidomastoid, and trapezius. Masticatory Muscle

Tenderness Score (MTS) and Cervical Muscle Tenderness Score (CTS) were calculated

separately, and combined as The Total Muscle Tenderness Score (TTS). The number of

tender muscles per patients was also recorded.

This article is protected by copyright. All rights reserved.

 Data analysis

Statistical analyses were performed using SPSS software version 22.0 (Chicago, IL, USA).
Accepted Article
Statistical significance was considered as P <0.05. Numerical variables were presented as

means and standard deviations, while categorized variables were presented as frequencies and

percentages.

Univariate analyses between muscle tenderness scores and the independent variables were

performed according to the data: Pearson’s correlation, analysis of variance (ANOVA) or

Student’s t-test and Bonferroni post hoc.

To examine the factors associated with MTS score in a multivariate manner, a conceptual

hierarchical multiple regression model was adopted 30. This method employs sequential

adjustments from distal to proximal determinants of a health condition, aiming to elucidate

their relationships 30. While conventional multivariable models, such as stepwise logistic

regression, are based solely on statistically significant explanatory factors, the hierarchical

conceptual analysis adopts a theoretical ordering, based on knowledge about social and

biological determinants of disease. The ordering of variables is determined according to the

hypothesis that some variables have confounding effects and others have modifying effects.

Previous studies have described this analytical approach 30,31.

Results

General description

The TMD group consisted of 192 patients and the control group had 99 subjects. Eight

patients in the TMD group and one in the control were excluded due to missing data.

Table 1 presents the demographic characteristics of the study population. The mean age of

the TMD group was 21.22±4.01 years; 79 (41.1%) were males and 113 (58.9 %) females.

This article is protected by copyright. All rights reserved.

 TMP was the most frequent diagnosis (n=122; 63.5%), followed by MMD (n=44; 22.9%) and

TMJ (n=26; 13.5%). There were no significant differences in of any of the demographic
Accepted Article
parameters between the TMD diagnoses (p>0.05).

The mean age of the control group was 20.81 ±1.49 years; 52 (52.5%) participants were

males and 47 (47.5%) were females (Table 1).

The TMD and control groups were matched for age and sex (p=0.3 and p=0.07, respectively)

(Table 1).

Tenderness Scores

ANOVA analysis and post hocs Bonferroni analysis of MTS, TTS and the number ‎of ‎

masticatory and total tender ‎muscles among the study population are presented in Tables 2

and3, respectively. As expected, MTS, TTS and the number ‎of ‎masticatory and total tender

‎muscles differed between TMD sub-groups and controls (p<0.001 for all muscle tenderness

scores) (Table 1).

There were no statistically significant differences in these tenderness scores between the

controls and the TMJD group (p=1.0) (Table3). Across TMD diagnostic categories, there

were no statistically significant differences in these tenderness scores between the MMD and

TMP groups (p=1.0) (Table3).

We created two groups within the TMJD group (N=26) :non-painful TMJD (N=14) and

painful TMJD (N=12). There were statistically significant differences in tenderness scores

between painful and non-painful TMJD as following: MTS (0.27±0.34 vs.0.00±0.00, p=0.02,

respectively), number ‎of ‎masticatory tender ‎muscles (1.00±1.28 vs 0.00±0.00, p=0.02), TTS

This article is protected by copyright. All rights reserved.

 (1.08 ±1.38 vs 0.00±0.00, p=0.02) and number ‎of ‎total (masticatory+cervical) tender ‎muscles

(1.00±1.28 vs 0.00±0.00, p=0.02).

Accepted Article
Tenderness scores demographics and clinical parameters

Univariate analysis of demographic and clinical parameters for the entire study group (N

=291) with statistically significant associations and correlations with the MTS, TTS and the

number ‎of ‎masticatory and total tender ‎muscles, are presented in Table 4 (ANOVA analysis

for categorical parameters) and Table 5 (Pearson Correlations (R) analysis for continuous

parameters). These include:

(1) Female sex (p<0.001 for all muscle tenderness scores).

(2) Grinding habit (MTS: p=0.002,TTS:p <0.001, the number ‎of ‎masticatory (p=0.045) and

total tender ‎muscles (p=0.010).

(3) Increasing levels of pain on opening (p<0.001 for all muscle tenderness scores).

According to POST HOC Bonferroni test, there were statistically significant differences

(p<0.05) in the all tenderness scores between patients without pain on opening (none) to

those with any level of pain on opening (i.e. mild,moderate and severe)(<0.001 for all) as

well as between mild to moderate pain on opening in the TTS (p=0.022).

(4) Co-morbid migraine, followed by TTH (MTS: p=0.006 ,TTS:p=0.022, the number ‎of ‎

masticatory (p=0.002) and total tender ‎muscles (p=0.005)According to POST HOC

Bonferroni test, there were statistically significant differences (p<0.05) in the muscles

tenderness scores only between patients with migraine to those without headache.

(5) Pain scores, including: VPS scores, longer onset, duration and more frequent pain

episodes (p<0.001 for all muscle tenderness scores), and co-morbid body pains: back ‎+‎

This article is protected by copyright. All rights reserved.

 periorbital ,followed by : neck +back, neck,periorbital,back and none (p<0.001 for all muscle

tenderness scores) (Tables 4 and5).

Accepted Article
Whiplash history was positively associated with TTS (p=0.006) and the number ‎of ‎total

tender ‎muscles (masticatory +cervical) score (p=0.024), but not with MTS (p=0.190) and the

number ‎of masticatory tender ‎muscles score (p=0.0228) (Table4).

Clenching habit was positively associated with all tenderness scores (MTS:P=0.010, the

number ‎of ‎masticatory (p=0.004 and total tender ‎muscles (p=0.0037), except for the TTS

(p=0.071) (Table4).

Results of the conceptual hierarchical multiple regression model for MTS

The univariate analysis demonstrated that the MTS score exhibited similar associations as the

TTS score, in agreement with the DC ⁄TMD. Therefore in the multivariate analysis we have

focused on the MTS score. To examine the factors associated with MTS score in a

multivariate manner, a conceptual hierarchical multiple regression model was adopted 30 . .

Results of the multiple regression model for dichotomized MTS by median are presented in

Table6. Our conceptual modeling assumed that TMD diagnosis was the most distal

determinant, while age and sex (1st model), pain characteristics (duration, frequency onset) (2nd

model), co-morbid pain conditions such as body pain and headaches (3rd model), and current

levels of VPS (4th model), were confounders or mediators in the relationship between TMD

diagnosis and MTS. Following this step, the associations between each explanatory variable

and MTS were assessed.

The 1st model adjusted the odds ratio (OR) of MTS dichotomized by median for age and sex,

the 2nd model additionally adjusted the OR for pain onset, attack duration, and frequency, the

This article is protected by copyright. All rights reserved.

 3rd model additionally adjusted for comorbid pain conditions while the 4th model additionally

adjusted for VPS. There was a significant reduction in the OR of MTS, with each step of the
Accepted Article
model (Table 5): according to the 2nd model by 31.5% (from OR of 2.66 to 1.82), 3rd model

by 22.5 % (from OR of 1.82 to 1.41), and 4th model by 8.5% (from OR of 1.41 to 1.29). The

total reduction of OR of MTS from 1st to 4th model was 51.5 % (from OR 2.66 to1.29).

Furthermore, the relationship between MTS and TMD diagnosis lost statistical significance

according to the 4th model (p=0.160). The reduction in the OR as well as the loss of

significance in the last model, suggests that these mediators underlie the differences in MTS

when sorted by TMD diagnosis and explained the association. Moreover, as can be seen from

Table6, the Nagelkerke R Square, representing the proportion of the total variability

explained by the model, increased with each step of the model (from 35.7% to 67.3%).

According to the 4th model, pain duration (p=0.007) and frequency (p=0.012), co-morbid

headaches (p=0.002) and body pain (p=0.005) retained their statistical significance with

MTS, implying that they are also directly related to higher MTS median scores (Table 5).

Finally, the data analysis pathway of this model is illustrated in Figure 1.

Discussion

The main findings of the present study are that pericranial muscle tenderness scores were

positively associated with the multiplicity of signs and symptoms. This may reflect the

positive associations between the muscle tenderness scores and disease severity as well as co-

existing pain conditions . The multivariate conceptual regression model suggests that MTS

may be a useful guide for treatment in TMD if taken together with VPS, onset, frequency and

duration of pain, and co-morbid pains such as headache and body pain. Only painful TMJD

patients, exhibited muscle tenderness scores, suggesting that the difference found between the

MMD and the TMJD is due to pain and not due to the diagnosis.These results are in line with

This article is protected by copyright. All rights reserved.

 the multivariate conceptual regression model for MTS where TMD diagnosis was associated

with MTS via parameters related to pain. Therefore, MTS, toghther with these parameters,
Accepted Article
may be used: (1) to distinguish between mild, moderate and severe MMD cases, (2) to assess

changes over time, (3) to explain concepts to the patient, (4) to assess treatment response (5)

for research (6) as a prognostic marker.

Indeed, the present-day concept is that TMD, in particular MMD, is a complicated entity, not

only localized to the orofacial area, but also involving structures beyond the masticatory

apparatus 32. Our findings are also consistent with the findings of the OPPERA study that

pain upon palpation of masticatory, neck, and body muscles predicted TMD incidence 32

The current DC-TMD classification system distinguishes between cases and non-cases but

does not establish MMD severity 27. Currently, we assess MMD severity numerically in terms

of pain, using the VPS. However, the VPS is not a specific tool for MMD, and may be used

to describe every pain Moreover, pain referral is very common in MMD 4, and patients may

indicate painful sites unrelated to the anatomical origin of the pain. This further emphasizes

the need for other measures, not just VPS, to assess MMD severity.

Whether pain causes muscle sensitivity or vice versa is currently unclear. Pericranial muscle

tenderness may reflect sensitization of peripheral nociceptors, or a dysfunction in higher

order supraspinal pain modulation systems rather than muscle tissue abnormalities 33. Trigger

points may stimulate the trigeminal nucleus caudalis and trigger a headache attack 33. Indeed,

muscle tenderness was shown to increase during cephalalgic attacks 34. Furthermore a higher

frequency of headaches causes increased muscle tenderness 35, especially among TTH

patients 36. In agreement, in the present study, higher tenderness scores were positively

associated with pain onset, frequency ,and duration. Moreover, parafunctional habits, such as

grinding and clenching, both associated with long-term overuse of peripheral muscles were

This article is protected by copyright. All rights reserved.

 also positively associated with the muscle tenderness scores (see Table4). On the other hand,

parafunction is considered secondary to muscle pain according to the pain adaptation model
Accepted Article
37
.

Interestingly, in the present study, patients with migraine exhibited the highest tenderness

scores compared to TTH. Muscle tenderness could be involved in migraine 3,20, attributed to

central sensitization 20. Nevertheless, the association between muscle tenderness scores and

headaches is particularly seen in TTH, where increased pericranial tenderness is recognized

as the most significant abnormal finding, with likely pathophysiological importance 1. It may

be not only responsible for the acute TTH episode but may also trigger central sensitization,

which leads to headache chronicization 2,3,33.

Although we described our patients presenting with TMD and headache as suffering from

"TMD and co-morbid headache", they can also be described as patients with "a headache and

co-morbid TMD". An overlap clearly exists between the International Headache Society

(IHS) diagnoses of "TTH with pericranial tenderness" and "Headache attributed to TMD". In

fact, TMD-headache comorbidity is bidirectional 38. The relationship between TMD and

headaches may be casual or may involve more complex pathophysiological and evolutionary

elements 38. Both diseases seem to share a common genetic base, and both exhibit peripheral

and central sensitization, manifested by the development of craniofacial allodynia and muscle

tenderness to palpation 1,38. Moreover, the same nociceptive system is involved in both

diseases, with chronic painful stimuli originating from trigeminal nerve endings running

along common pathways to the central nervous system. Additionally, pain modulation in both

diseases involves the thalamus, brainstem nuclei, sensitive cortex, and limbic system 38. Due

to these similarities, it may be that MMD represents a facial variant of "TTH with pericranial

tenderness" similar to the concept of Orofacial Migraine, which had been currently

recognised as the facial variant of migraine in the recent edition of the Headache

This article is protected by copyright. All rights reserved.

 Classification Committee of the International Headache Society. 21. Nevertheless, differences

between MMD and TTH exist: unlike TTH, MMD is characterized by unilateral, constant
Accepted Article
pain, that is present with jaw function. Further studies are needed to explore the TMD-

headache comorbidity and overlapping features.

The major strengths of the current study are the large sample size (291 patients) and the

uniform protocol utilizing the standardized VPS scores and the validated RDC/TMD,

allowing comparison with other ethnic groups. We minimized confounders such as aging and

illness. A clinical examination was also performed in the control group, which allows the

comparison with subclinical TMD cases. Additionally, TMD and control groups included

treatment-seeking patients in the dental setting. Since TMD patients often consult dentists 4,

our control group seems a more valid compared to the general population 39.

Limitations of this study include the possibility of selection bias of this convenience cohort.

However, patients were referred from multiple clinics serving different populations Due to

the case-control study design, we cannot assume causality, and therefore this paper only

suggests associations between the variables.

Conclusions:

Routine patient workup should include the MTS, to assess MMD severity and changes over

time as well as treatments response and as a research tool. MTS can be used as a common

methodology to describe both headaches and masticatory muscle disorders and to facilitate

interprofessional research and crosstalk between headache and orofacial pain practitioners.

This article is protected by copyright. All rights reserved.

 Legends to Tables

Table 1: Demographic characteristics of the study populationTable2: ANOVA analysis

Accepted Article
of muscle tenderness scores and the number of tender muscles among the study
population

MMD: patients with Masticatory muscle disorders

TMJD: patients with Temporomandibular joint disorders

TMP: patients with both MMD and TMJ

MTS: Masticatory muscles tenderness score

TTS: Total tenderness score

Table3: POST HOC Bonferroni analysis of muscles tenderness scores among the study
population

Table4: ANOVA analysis of tenderness scores and the number of tender muscles versus
demographic and clinical parameters
MMD: patients with Masticatory muscle disorders

TMJD: patients with Temporomandibular joint disorders

TMP: patients with both MMD and TMJ

MTS: Masticatory muscles tenderness score

TTS: Total tenderness score

SD: standard deviation

Table5: Pearson Correlations (R) of studied parameters with tenderness scores and the
number of tender muscles in the study population

MTS: Masticatory muscles tenderness score

TTS: Total tenderness score

Table6: Results of a conceptual hierarchical multiple logistic regression model for MTS

OR- odds ratio

CI- confidence interval

This article is protected by copyright. All rights reserved.

 * OR of MTS dichotomized by median adjusted for age and sex, additionally adjusted for pain
characteristics (duration, frequency, onset) (2nd model), comorbid pain conditions (body pain and
Accepted Article
co-morbid headaches) (3rd model) and for pain intensity (current levels of VPS) (4th model).

Figure 1 – A pathway model for TMD diagnosis as a distal determinant affecting the
MTS

Each of the contributors provided substantive intellectual contribution to one or more of the activities
related to this manuscript as follows:

Galit Almoznino - Corresponding author, the principal investigator, made substantial contributions
to the study's conception and design, acquisition of data, and analysis and interpretation of data;
drafted the submitted the article and provided final approval of the version to be published.

Avraham Zini -analysis and interpretation of data and approved the manuscript.

Zakuto Avraham -Data collection of the TMD group and approved the manuscript.

Hulio Slutzky -Data collection of the control group and approved the manuscript

Stav Bekker -Interpretation of the results revised and approved the manuscript.

Boaz Shay - revised and approved the manuscript.

Yaron Haviv -revised and approved the manuscript.

Yair Sharav -Interpretation of the results revised and approved the manuscript.

Rafael Benoliel –made substantial contributions to the study's conception and design, interpretation
of data, drafted, revised and approved the manuscript.

This article is protected by copyright. All rights reserved.

 Bibliography:
1. The International Classification of Headache Disorders, 3rd edition (beta version).
Cephalalgia. 2013;33(9):629-808.
2. Bendtsen L, Ashina S, Moore A, Steiner TJ. Muscles and their role in episodic tension-type
Accepted Article
headache: implications for treatment. Eur J Pain. 2015.
3. Rota E, Mongini F. Muscle tenderness and psychiatric comorbidity: a vicious cycle in
migraine chronicization. Front Neurol. 2014;5:148.
4. Schiffman E, Ohrbach R, Truelove E, et al. Diagnostic Criteria for Temporomandibular
Disorders (DC/TMD) for Clinical and Research Applications: recommendations of the
International RDC/TMD Consortium Network* and Orofacial Pain Special Interest
Groupdagger. J Oral Facial Pain Headache. 2014;28(1):6-27.
5. Tjakkes GH, Reinders JJ, Tenvergert EM, Stegenga B. TMD pain: the effect on health related
quality of life and the influence of pain duration. Health Qual Life Outcomes. 2010;8:46.
6. Almoznino G, Zini A, Zakuto A, et al. Oral Health-Related Quality of Life in Patients with
Temporomandibular Disorders. J Oral Facial Pain Headache. 2015;29(3):231-241.
7. Amin Hel S. Relationship between overall and abdominal obesity and periodontal disease
among young adults. East Mediterr Health J. 2010;16(4):429-433.
8. Dworkin SF, LeResche L. Research diagnostic criteria for temporomandibular disorders:
review, criteria, examinations and specifications, critique. J Craniomandib Disord.
1992;6(4):301-355.
9. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-
Summary Report 2007. J Allergy Clin Immunol. 2007;120(5 Suppl):S94-138.
10. Benoliel R, Sharav Y. Tender muscles and masticatory myofascial pain diagnosis: how many
or how much? J Orofac Pain. 2009;23(4):300-301.
11. Christensen MB, Bendtsen L, Ashina M, Jensen R. Experimental induction of muscle
tenderness and headache in tension-type headache patients. Cephalalgia.
2005;25(11):1061-1067.
12. Mongini F, Ciccone G, Ceccarelli M, Baldi I, Ferrero L. Muscle tenderness in different types of
facial pain and its relation to anxiety and depression: A cross-sectional study on 649
patients. Pain. 2007;131(1-2):106-111.
13. Mongini F, Rota E, Deregibus A, Mura F, Francia Germani A, Mongini T. A comparative
analysis of personality profile and muscle tenderness between chronic migraine and chronic
tension-type headache. Neurol Sci. 2005;26(4):203-207.
14. Fernandez-de-Las-Penas C, Cuadrado ML, Arendt-Nielsen L, Pareja JA. Side-to-side
differences in pressure pain thresholds and pericranial muscle tenderness in strictly
unilateral migraine. European Journal of Neurology. 2008;15(2):162-168.
15. Fernandez-de-las-Penas C, Cuadrado ML, Barriga FJ, Pareja JA. Pericranial tenderness is not
related to nummular headache. Cephalalgia. 2007;27(2):182-186.
16. Langemark M, Olesen J. Pericranial tenderness in tension headache. A blind, controlled
study. Cephalalgia. 1987;7(4):249-255.
17. de Tommaso M, Delussi M, Vecchio E, Sciruicchio V, Invitto S, Livrea P. Sleep features and
central sensitization symptoms in primary headache patients. J Headache Pain. 2014;15:64.
18. Jensen R, Rasmussen BK. Muscular disorders in tension-type headache. Cephalalgia.
1996;16(2):97-103.
19. Lipchik GL, Holroyd KA, Talbot F, Greer M. Pericranial muscle tenderness and exteroceptive
suppression of temporalis muscle activity: a blind study of chronic tension-type headache.
Headache. 1997;37(6):368-376.
20. Aaseth K, Grande RB, Lundqvist C, Russell MB. Pericranial tenderness in chronic tension-type
headache: the Akershus population-based study of chronic headache. J Headache Pain.
2014;15:58.

This article is protected by copyright. All rights reserved.

 21. Headache Classification Committee of the International Headache Society (IHS) The
International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-
211.
22. Inoue E, Maekawa K, Minakuchi H, et al. The relationship between temporomandibular joint
Accepted Article
pathosis and muscle tenderness in the orofacial and neck/shoulder region. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod. 2010;109(1):86-90.
23. Silveira A, Gadotti IC, Armijo-Olivo S, Biasotto-Gonzalez DA, Magee D. Jaw dysfunction is
associated with neck disability and muscle tenderness in subjects with and without chronic
temporomandibular disorders. Biomed Res Int. 2015;2015:512792.
24. Benoliel R, Zini A, Zakuto A, et al. Subjective Sleep Quality in Temporomandibular Disorder
Patients and Association with Disease Characteristics and Oral Health-Related Quality of Life.
J Oral Facial Pain Headache. 2017;31(4):313-322.
25. Abramson JH. WINPEPI (PEPI-for-Windows): computer programs for epidemiologists.
Epidemiol Perspect Innov. 2004;1(1):6.
26. Schiffman EL, Ohrbach R, Truelove EL, et al. The Research Diagnostic Criteria for
Temporomandibular Disorders. V: methods used to establish and validate revised Axis I
diagnostic algorithms. J Orofac Pain. 2010;24(1):63-78.
27. Schiffman EL, Truelove EL, Ohrbach R, et al. The Research Diagnostic Criteria for
Temporomandibular Disorders. I: overview and methodology for assessment of validity. J
Orofac Pain. 2010;24(1):7-24.
28. Almoznino G, Zini A, Zakuto A, et al. Oral Health-Related Quality of Life in Patients with
Temporomandibular Disorders. J Oral Facial Pain Headache. 2015;29(3):231-241.
29. Sharav Y, Benoliel R. Orofacial Pain and Headache. Second ed. Chicago: Quintessence; 2015.
30. Victora CG, Huttly SR, Fuchs SC, Olinto MT. The role of conceptual frameworks in
epidemiological analysis: a hierarchical approach. Int J Epidemiol. 1997;26(1):224-227.
31. Almoznino G, Aframian DJ, Sharav Y, Sheftel Y, Mirzabaev A, Zini A. Lifestyle and dental
attendance as predictors of oral health-related quality of life. Oral Dis. 2015;21(5):659-666.
32. Slade GD, Fillingim RB, Sanders AE, et al. Summary of findings from the OPPERA prospective
cohort study of incidence of first-onset temporomandibular disorder: implications and
future directions. J Pain. 2013;14(12 Suppl):T116-124.
33. Fernandez-de-Las-Penas C. Myofascial Head Pain. Curr Pain Headache Rep. 2015;19(7):28.
34. Jensen R, Bendtsen L, Olesen J. Muscular factors are of importance in tension-type
headache. Headache. 1998;38(1):10-17.
35. Goncalves DA, Speciali JG, Jales LC, Camparis CM, Bigal ME. Temporomandibular symptoms,
migraine, and chronic daily headaches in the population. Neurology. 2009;73(8):645-646.
36. Jensen R. Pathophysiological mechanisms of tension-type headache: a review of
epidemiological and experimental studies. Cephalalgia. 1999;19(6):602-621.
37. Lund JP, Donga R, Widmer CG, Stohler CS. The pain-adaptation model: a discussion of the
relationship between chronic musculoskeletal pain and motor activity. Can J Physiol
Pharmacol. 1991;69(5):683-694.
38. Speciali JG, Dach F. Temporomandibular dysfunction and headache disorder. Headache.
2015;55 Suppl 1:72-83.
39. Coghill RC, Yarnitsky D. Healthy and normal? The need for clear reporting and flexible criteria
for defining control participants in quantitative sensory testing studies. Pain.
2015;156(11):2117-2118.

This article is protected by copyright. All rights reserved.

 Table 1: Demographic characteristics of the study population
Accepted Article
Parameter Values Mean age ± SD P value

Study groups TMD group (n=192) 21.22±4.01

0.332
(n=291) Control group (n=99) 20.81 ±1.49
MMD (n=44) 21.86±5.64
TMD group (n=192) TMJ (n=26) 21.31±3.77 0.356
TMP (n=122) 20.97±3.30
Parameter Values Females :N(%) Males (N,%) P value
Study groups TMD group (n=192) 113 (58.9 %) 79 (41.1%)
0.07
(n=291) Control group (n=99) 47 (47.5%) 52 (52.5%)
MMD (n=44) 21 (47.7) 23 (52.3)
TMD group (n=192) TMJ (n=26) 13 (50) 13 (50) 0.089
TMP (n=122) 79 (35.2) 43 (35.2)

This article is protected by copyright. All rights reserved.

 Table2: ANOVA analysis of muscle tenderness scores and the number of tender muscles
among the study population
Accepted Article
Muscle tenderness Study N Mean SD P value
scores
group between all
groups

MTS Control 99 0.36 1.14

MMD 44 2.59 2.01
TMJD 26 0.50 1.06 <0.001
TMP 122 2.51 2.11
Total 291 1.61 2.03
Number ‎of ‎masticatory Control 99 0.28 .850
tender ‎muscles MMD 44 1.84 1.29
TMJD 26 0.46 .980 <0.001
TMP 122 1.68 1.14
Total 291 1.12 1.27
TTS Control 99 0.47 1.52
MMD 44 3.97 3.95
TMJD 26 0.50 1.06 <0.001
TMP 122 3.69 3.50
Total 291 2.35 3.31
Number ‎of ‎total tender Control 99 0.38 1.29
‎muscles MMD 44 2.88 2.60
masticatory+cervical)) TMJD 26 0.46 .980 <0.001
TMP 122 2.49 2.04
Total 291 1.65 2.14

This article is protected by copyright. All rights reserved.

 Table 3 : POST HOC Bonferroni analysis of muscles tenderness scores among the
study population
Accepted Article
(I) (J) Mean P 95% Confidence Interval
Dependent Variable Diagnosis Diagnosis Difference (I-J) Std. Error value
Lower Upper
Bound Bound
MTS MMD -2.22* .31 <0.001 -3.06 -1.38

Control TMJD -.13 .38 1.000 -1.15 .88

TMP -2.15* .23 <0.001 -2.77 -1.52

TMJD 2.09* .43 <0.001 .94 3.23

MMD
TMP .074 .30 1.000 -.74 .88

TMJD TMP -2.01* .37 <0.001 -3.01 -1.01

Number ‎of ‎masticatory MMD -1.55* .19 <0.001 -2.07 -1.04

tender ‎muscles Control TMJD -.178 .23 1.000 -.80 .44

TMP -1.39* .14 <0.001 -1.78 -1.01

TMJD 1.37* .26 <0.001 .67 2.08

MMD
TMP .16 .18 1.000 -.33 .65

TMJD TMP -1.22* .23 <0.001 -1.83 -.60

TTS Control MMD -3.50* .52 <0.001 -4.89 -2.10

TMJD -.02 .63 1.000 -1.72 1.67

TMP -3.22* .39 <0.001 -4.26 -2.17

MMD TMJD 3.47* .71 <0.001 1.57 5.38

TMP .28 .51 1.000 -1.07 1.63

TMJD TMP -3.19* .62 <0.001 -4.86 -1.53

Number ‎of ‎total tender Control MMD -2.50* .33 <0.001 -3.39 -1.60
‎muscles
TMJD -.07 .41 1.000 -1.16 1.00
(masticatory+cervical)
TMP -2.10* .251 <0.001 -2.77 -1.44

MMD TMJD 2.42* .45 <0.001 1.20 3.64

TMP .39 .32 1.000 -.47 1.26

TMJD TMP -2.03* .40 <0.001 -3.09 -.96

This article is protected by copyright. All rights reserved.

 Table 4: ANOVA analysis of tenderness scores and the number of tender muscles versus
demographic and clinical parameters
Accepted Article
Mean tenderness scores ± SD
MTS Number ‎of TTS Number ‎of ‎total
Parameter Values ‎ asticatory
m tender ‎muscles
tender ‎muscles (masticatory
+cervical)

Females 2.0±2.3 1.3±1.3 3.0±3.8 2.0±2.3

Sex Males 1.1±1.5 0.8±1.1‎of
Number 1.5±2.2 1.1±1.7
p <0.001 ‎masticatory
0.001 <0.001 <0.001
Whiplash‎ Yes 2.8±2.1 tender
1.8±1.3 6.4±4.6 3.8±2.6
No 1.5±2.0 ‎m uscles
1.1±1.2 2.2±3.2 1.6±2.1
p‎‎ 0.190 0.228 0.006 0.024
Clenching Yes 2.0±2.1 1.4±1.3 2.8±3.5 2.0±2.3
No 1.3±1.9 0.9±1.2 2.1 ±3.2 1.4±2.0
habit
p 0.010 0.004 0.071 0.037
‎
Grinding habit Yes 2.3±2.0 2.4±2.0 3.2 ±3.2 2.3±2.1
No 1.4±2.0 1.4±2.0 2.1±3.3 1.5±2.1
p‎ 0.002 <0.001 0.045 0.010
Pain None 0.7±1.4 0.6±1.0 1.0±2.3 0.8±1.6
Mild 2.0±1.9 1.5±1.3 2.8±3.0 2.1±2.2
on opening
Moderate 2.9 ±2.2 1.8±1.2 4.4±4.2 2.9±2.4
Severe 3.2 ±2.5 1.8±1.1 4.6±4.1 2.6±1.9
p‎ <0.001 <0.001 <0.001 <0.001
Migrane 3.4 ±2.6 2.1±1.4 5.5 ±4.7 3.6±2.7
Co-morbid TTH 2.6±1.8 1.8±1.2 3.5 ±3.4 2.5±2.1
headache ‎ None 2.0±1.9 1.4±1.2 2.9±3.2 2.1 ±2.0
p 0.006 0.022 0.002 0.005
Body pain None 1.2 ±1.9 0.8±1.1 1.5±2.5 1.0±1.5
Back pain 1.3±1.6 0.9±1.0 1.7±2.5 1.2±1.5
Periorbital 2.0±2.6 1.3±1.8 4.4±5.6 2.8±3.7
Neck pain 2.3±1.7 1.8±1.3 4.2±3.3 3.3±2.8
Neckl‎+‎back 2.4±2.2 1.6±1.2 5.8±5.9 3.7±3.3
Back ‎+‎Periorbital ‎ 4.0±0.0 3.0±0.0 6.0±0.0 5.0±0.0
p‎ <0.001 <0.001 <0.001 <0.001
Body pain Yes 2.0±2.1 1.4±1.3 3.2±3.8 2.3±2.4
(yes/no) No 1.2±1.9 0.8±1.1 1.5±2.5 1.0±1.5
p‎ <0.001 <0.001 <0.001 <0.001

This article is protected by copyright. All rights reserved.

 Table5: Pearson Correlations (R) of studied parameters with tenderness scores and the
number of tender muscles in the study population
Accepted Article
MTS Number ‎of TTS Number ‎of ‎total
‎ asticatory
m tender ‎muscles
tender ‎muscles (masticatory
+cervical)
Age Pearson Correlation -.035 .006 .003 .043
Sig. (2-tailed) .5510 .9170 .9640 .4660
N 291 291 291 291
Frequency of Pearson Correlation -.411 -.407 -.402 -.402
Pain episodes
Sig. (2-tailed) <0.001 <0.001 <0.001 <0.001
N 290 290 290 290
Duration of Pearson Correlation -.382 -.416 -.359 -.359
pain episodes
Sig. (2-tailed) <0.001 <0.001 <0.001 <0.001
N 290 290 290 290
Onset of pain Pearson Correlation -.290 -.291 -.240 -.240
Sig. (2-tailed) <0.001 <0.001 <0.001 <0.001
N 291 291 291 291
Verbal pain Pearson Correlation .605 .599 .546 .546
scores (VPS)
Sig. (2-tailed) <0.001 <0.001 <0.001 <0.001
N 291 291 291 291

This article is protected by copyright. All rights reserved.

Accepted Article

This article is protected by copyright. All rights reserved.

Accepted Article

This article is protected by copyright. All rights reserved.