Primary Headache DisordersHEAD-TMDNCT07514208
Pericranial and General Sensitivity in Patients With Primary Headache
An observational study of Primary Headache Disorders and Tension Headache, run by Universitat Internacional de Catalunya at 1 site in Spain.
Trial summary
Primary headaches such as migraine and tension type headache are among the most common neurological disorders and frequently cause significant disability and reduced quality of life. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Primary Headache Disorders, Tension Headache, Tension-type Headache
- What is being tested?
- Pericranial Tenderness Assessment, Pressure Pain Threshold Assessment and Temporomandibular Disorder Assessment
- How many people
- 120 participants
- Where
- 1 siteSpain
- Study dates
- 31 Mar 2026to Jun 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study population will consist of adults recruited from neurology and orofacial pain clinical settings as well as from the general population. Participants with primary headache disorders will be recruited through headache specialists and clinicians working in participating centers. Eligible patients must have a confirmed diagnosis of primary headache according to the International Classification of Headache Disorders third edition and be under stable medical treatment. Healthy control participants will be recruited from the community, including students and university staff, and will be screened using a structured questionnaire to exclude individuals with clinically relevant headache disorders. All participants will be adults able to understand the study procedures and provide informed consent. Recruitment will take place at clinical and academic centers in Spain and Germany.
Who may be able to join
- Adults diagnosed with primary headache disorders, including migraine or tension-type headache, according to the International Classification of Headache Disorders third edition.
- Diagnosis confirmed by a headache specialist.
- Stable medical treatment for headache for at least six months prior to participation.
- Ability to understand and communicate in Spanish, English, or German.
- Ability to provide written informed consent.
Who cannot join
- Presence of secondary headache disorders or clinical suspicion of secondary headache based on screening criteria.
- Recent onset of undiagnosed headache or unilateral neck pain associated with neurological or neuropathic symptoms.
- Severe dermatological conditions or injuries affecting the head, neck, or intraoral region that could interfere with clinical examination.
- Recent fractures affecting the head or cervical region.
- Previous diagnosis of uncontrolled psychiatric disorders or neurodegenerative diseases.
- Pregnancy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Pericranial and General Sensitivity in Patients With Primary Headache: a Multicenter Case-control Study
Primary headaches such as migraine and tension type headache are among the most common neurological disorders and frequently cause significant disability and reduced quality of life. Increasing evidence suggests that these headaches may share biological mechanisms with temporomandibular disorders, a group of conditions affecting the jaw muscles and temporomandibular joint. Both conditions are also often associated with other chronic pain disorders, suggesting that altered pain processing and sensitization of the nervous system may play an important role in their development.
Despite these observations, few studies have simultaneously evaluated local muscle tenderness around the head and neck, generalized pain sensitivity in other parts of the body, and the presence of additional chronic pain conditions in patients with primary headaches. Understanding how these factors interact may help clarify why some patients develop more severe or persistent headache disorders and may improve future diagnostic and treatment strategies.
Read more
The aim of this multicenter observational study is to compare patients with primary headaches to healthy individuals without headaches. The study will assess sensitivity of muscles around the head and neck, general pain sensitivity at distant body sites, the presence of temporomandibular disorders, and the number of other chronic pain conditions. Participants will also complete questionnaires about pain symptoms and related health conditions.
Participants will undergo a clinical examination performed by trained clinicians, including manual assessment of tenderness in head and neck muscles and measurement of pressure pain thresholds using a handheld device. Additional evaluations will include standardized questionnaires about pain intensity, pain distribution, and symptoms related to central sensitization. Cervical motor and sensorimotor function will also be evaluated using a wearable sensor system.
By comparing individuals with primary headaches and healthy controls, the study aims to better understand the relationship between headache disorders, jaw related pain conditions, and general pain sensitivity. The results may contribute to improved clinical assessment and a more comprehensive understanding of the mechanisms underlying headache and related pain disorders.
Read the detailed description
Primary headaches are among the most prevalent neurological disorders worldwide and represent a major cause of disability and reduced quality of life. Migraine and tension type headache are the most common forms and are characterized by complex pathophysiological mechanisms involving peripheral and central nervous system processes. These mechanisms include altered nociceptive processing, dysfunction of endogenous pain modulation systems, neurovascular interactions, and neuroinflammatory responses.
Temporomandibular disorders are musculoskeletal conditions affecting the temporomandibular joint, masticatory muscles, and associated structures. Previous research has shown that temporomandibular disorders frequently coexist with primary headaches. Both conditions share anatomical and neurophysiological pathways through the trigeminal system, which may contribute to overlapping clinical manifestations and mutual influence between disorders. In addition, individuals with temporomandibular disorders or headaches often present with other chronic overlapping pain conditions such as low back pain, fibromyalgia, irritable bowel syndrome, or chronic fatigue syndrome. This broader pattern of comorbidity has been associated with altered pain sensitivity and central sensitization mechanisms.
Experimental and clinical studies have demonstrated that patients with primary headaches and temporomandibular disorders often exhibit increased tenderness of pericranial and cervical muscles as well as reduced pressure pain thresholds both locally and at distant anatomical sites. These findings suggest the presence of peripheral sensitization in local tissues together with generalized hypersensitivity reflecting central sensitization processes. However, previous studies have often assessed these mechanisms separately, have used heterogeneous methodologies, and have rarely evaluated headache disorders and temporomandibular disorders simultaneously using standardized diagnostic criteria.
The present study aims to address these limitations through a multicenter observational design conducted in Spain and Germany. The study will compare individuals diagnosed with primary headache to healthy control participants without clinically relevant headache symptoms. The primary objective is to evaluate differences in pericranial muscle tenderness and generalized pressure pain sensitivity between these groups. Additional objectives include exploring the association between the number of chronic overlapping pain conditions and measures of pain sensitization, and examining the coexistence between primary headaches and temporomandibular disorders.
Participants with primary headache will be diagnosed according to the International Classification of Headache Disorders third edition by headache specialists. Temporomandibular disorders will be assessed using the Diagnostic Criteria for Temporomandibular Disorders. Pain sensitivity will be evaluated through standardized manual palpation of pericranial muscles using the Total Tenderness Score and by measuring pressure pain thresholds at extra trigeminal anatomical sites with digital algometry. Additional clinical variables will include self reported pain intensity, pain distribution, and symptoms associated with central sensitization. Cervical motor and sensorimotor function will also be assessed using a wearable sensor based measurement system that records cervical movement patterns and proprioceptive performance during standardized tests.
By integrating clinical examination, quantitative sensory testing, and standardized questionnaires within the same protocol, the study aims to provide a comprehensive characterization of pain sensitivity and comorbidity patterns in patients with primary headache. The results may improve understanding of the relationship between headache disorders, temporomandibular disorders, and generalized pain sensitization, and may contribute to the development of more comprehensive diagnostic and therapeutic approaches for individuals with complex pain presentations.
- Conditions
- Primary Headache Disorders, Tension Headache, Tension-type Headache, Migraine, Chronic Overlapping Pain Disorders
- Being tested
- Pericranial Tenderness Assessment, Pressure Pain Threshold Assessment, Temporomandibular Disorder Assessment, Patient-Reported Outcome Assessment, Cervical Function Assessment
- Keywords
- Primary headache, Migraine, Tension-type headache, Temporomandibular disorders, Pericranial tenderness, Pressure pain threshold, Central sensitization, Chronic overlapping pain conditions, Quantitative sensory testing, Multicenter observational study
- Medical subject headings
- Headache Disorders, Primary, Tension-Type Headache, Migraine Disorders, Temporomandibular Joint Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pericranial Tenderness AssessmentDiagnostic test
Also called TTS, Pericranial Tenderness Examination
Pericranial tenderness will be assessed using the Total Tenderness Score, a standardized clinical examination based on manual palpation of pericranial and cervical muscles. Bilateral palpation will be performed on eight pairs of muscle bodies and insertions including the masseter, temporalis, frontal muscle, coronoid process, upper trapezius, sternocleidomastoid, suboccipital muscles, and mastoid process. Palpation will be applied with approximately 1 kg of pressure using the second and third fingertips rotated for four to five seconds. Participant responses will be rated using a four point scale ranging from 0 (no tenderness) to 3 (severe tenderness with withdrawal or pronounced facial reaction). The sum of all responses will generate the Total Tenderness Score, with a maximum possible score of 48. This assessment is commonly used to quantify pericranial muscle tenderness in patients with headache and temporomandibular disorders.
Pressure Pain Threshold AssessmentDiagnostic test
Also called PPT, Pressure Pain Threshold, Pressure Algometry
Pressure pain thresholds will be assessed using a handheld digital algometer equipped with a 1 cm² probe. The probe will be positioned perpendicular to the skin at predefined extra trigeminal anatomical sites including the tibialis anterior muscle, the radial carpal extensor region at the dorsal wrist joint line, and the interspinous space between L5 and S1. Pressure will be progressively applied at a constant rate following visual guidance provided by the device interface. Participants will be instructed to indicate the moment when the sensation changes from pressure to pain. Three measurements will be obtained at each anatomical site with a resting interval between assessments. The mean value of the repeated measurements will be recorded and used to quantify generalized mechanical pain sensitivity.
Temporomandibular Disorder AssessmentDiagnostic test
Also called DC/TMD, Diagnostic Criteria for Temporomandibular Disorders
Pain related temporomandibular disorders will be assessed using the standardized Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) clinical protocol. The examination includes structured assessment of temporomandibular joint pain, masticatory muscle pain, mandibular movement, joint sounds, and pain during functional movements or palpation. Based on the DC/TMD diagnostic algorithms, participants will be classified into pain related temporomandibular disorder categories including arthralgia, myalgia, combined myalgia and arthralgia, or headache attributed to temporomandibular disorder. The examination will be performed by trained clinicians following the validated DC/TMD protocol.
Patient-Reported Outcome AssessmentDiagnostic test
Also called Self-Reported Questionnaires, Patient Questionnaires
Participants will complete standardized self-reported questionnaires to assess pain related symptoms and associated health conditions. These will include the Central Sensitization Inventory to evaluate symptoms associated with central sensitization, the Brief Pain Inventory Short Form to assess pain intensity and pain related interference with daily activities, and a body pain drawing to document the distribution of pain. Additional questions will collect information on the presence and duration of physician-diagnosed chronic overlapping pain conditions. The questionnaires will be administered through a secure electronic data collection platform prior to or during the clinical assessment.
Cervical Function AssessmentDiagnostic test
Also called NeckCare Assessment, Cervical Range of Motion Assessment, Cervical Sensorimotor Function Test, Cervical function will be assessed using the NeckCare system, a wearable sensor-based platform designed to measure cervical spine kinematics and sensorimotor control. The system uses a lightweight hea
Cervical function will be assessed using the NeckCare system, a wearable sensor-based platform designed to measure cervical spine kinematics and sensorimotor control. The system uses a lightweight head-mounted sensor connected to a computer interface that records cervical movement in real time. Active cervical range of motion will be measured for flexion, extension, right and left rotation, and right and left lateral flexion. Cervical proprioception will be evaluated using the Joint Position Error test, in which participants attempt to reposition the head to a neutral position without visual feedback after performing active cervical movements. Sensorimotor control will also be assessed using the Butterfly Test, which requires participants to follow a moving visual target with head movements while the system quantifies movement accuracy, coordination, and smoothness.
Multimodal Clinical AssessmentDiagnostic test
Also called Comprehensive Pain Assessment, Multidimensional Clinical Evaluation
Participants will undergo a standardized multimodal clinical assessment designed to characterize pain sensitivity and related clinical variables. The assessment will include evaluation of pericranial muscle tenderness using the Total Tenderness Score, measurement of extra trigeminal pressure pain thresholds with digital algometry, and clinical examination for temporomandibular disorders using the Diagnostic Criteria for Temporomandibular Disorders protocol. Participants will also complete validated patient reported outcome measures assessing central sensitization symptoms, pain intensity, pain related interference, and distribution of pain. In addition, cervical spine function will be evaluated through objective measurement of cervical range of motion, proprioception, sensorimotor control, and cervical flexor muscle strength and endurance using wearable sensor technology and digital dynamometry. This integrated evaluation provides a comprehensive characterization of local and generaliz
| Study group | Role | What they receive |
|---|---|---|
| Primary Headache | Participants diagnosed with primary headache disorders according to the International Classification of Headache Disorders third edition. Diagnosis will be confirmed by a headache specialist. Participants may include individuals with migraine or tension type headache and will undergo standardized clinical assessment including evaluation of pericranial tenderness, pressure pain thresholds, temporomandibular disorders, and pain related questionnaires. Receives: Diagnostic Test: Pericranial Tenderness Assessment; Diagnostic Test: Pressure Pain Threshold Assessment; Diagnostic Test: Temporomandibular Disorder Assessment; Diagnostic Test: Patient-Reported Outcome Assessment; Diagnostic Test: Cervical Function Assessment; Diagnostic Test: Multimodal Clinical Assessment | |
| Healthy subjects | Healthy volunteers without clinically relevant headache after screening using a questionnaire based on the International Classification of Headache Disorders criteria. Participants who meet criteria for possible headache disorders will be excluded or referred for medical evaluation. Healthy controls will undergo the same clinical assessments as the case group to allow comparison of pain sensitivity and related clinical variables. Receives: Diagnostic Test: Pericranial Tenderness Assessment; Diagnostic Test: Pressure Pain Threshold Assessment; Diagnostic Test: Temporomandibular Disorder Assessment; Diagnostic Test: Patient-Reported Outcome Assessment; Diagnostic Test: Cervical Function Assessment; Diagnostic Test: Multimodal Clinical Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Pericranial Tenderness Score
Pericranial tenderness will be quantified using the Total Tenderness Score obtained through standardized manual palpation of bilateral cranial and cervical muscles. Eight pairs of anatomical sites will be examined, and responses will be rated on a four point scale ranging from 0 (no tenderness) to 3 (severe tenderness with withdrawal or pronounced facial reaction). The total score ranges from 0 to 48, with higher values indicating greater pericranial muscle tenderness.
Measured: Baseline assessment during the study visit.
Extra-Trigeminal Pressure Pain Threshold
Generalized pain sensitivity will be assessed through pressure pain threshold measurements using a handheld digital algometer at extra-trigeminal anatomical sites including the tibialis anterior muscle, the radial carpal extensor region, and the interspinous space between L5 and S1. Participants will indicate the point at which pressure becomes painful. Three measurements will be obtained at each site and the mean value will be used for analysis. Lower pressure pain threshold values indicate increased mechanical pain sensitivity.
Measured: Baseline assessment during the study visit.
Secondary outcomes (5)
Presence of pain related temporomandibular disorders according to DC/TMD
The presence of pain related temporomandibular disorders will be determined using the Diagnostic Criteria for Temporomandibular Disorders clinical examination protocol. Participants will be classified according to the DC/TMD diagnostic algorithms into categories including arthralgia, myalgia, combined myalgia and arthralgia, or headache attributed to temporomandibular disorder.
Measured: Baseline assessment during the study visit.
Central Sensitization Inventory Score
Symptoms associated with central sensitization will be assessed using the Central Sensitization Inventory Part A. The questionnaire contains 25 items scored on a five point Likert scale generating a total score ranging from 0 to 100. Higher scores indicate greater symptom burden related to central sensitization.
Measured: Baseline assessment during the study visit.
Central Sensitization Related Comorbid Conditions
Part B of the Central Sensitization Inventory will be used to record previously diagnosed chronic pain or central sensitivity related conditions reported by participants. These conditions include disorders commonly associated with central sensitization such as fibromyalgia, irritable bowel syndrome, migraine, chronic fatigue syndrome, temporomandibular disorders, and other physician diagnosed chronic pain conditions. The total number of reported conditions will be used to characterize the burden of comorbid pain disorders.
Measured: Baseline assessment during the study visit.
Pain Intensity and Pain Interference
Pain severity and the impact of pain on daily functioning will be assessed using the Brief Pain Inventory Short Form. The instrument provides numerical rating scales ranging from 0 to 10 for pain intensity and pain interference, where higher scores indicate greater pain burden.
Measured: Baseline assessment during the study visit.
Pain Distribution
The distribution of pain will be documented using a body pain drawing completed by participants. The drawing will allow identification of localized or widespread pain patterns and will be used to characterize the presence of multisite pain.
Measured: Baseline assessment during the study visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2026
- Study start31 Mar 2026 (estimated)
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Primary Headache DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitat Internacional de Catalunya
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jordi Tomàs Aliberas, International University of Catalonia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07514208
- Sponsor's protocol ID
- REST-ECL-2025-01
- Acronym
- HEAD-TMD
- Status last verified
- Apr 2026
- First submitted
- 12 Mar 2026
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Glaros AG, Urban D, Locke J. Headache and temporomandibular disorders: evidence for diagnostic and behavioural overlap. Cephalalgia. 2007 Jun;27(6):542-9. doi: 10.1111/j.1468-2982.2007.01325.x. Epub 2007 Apr 18.
PubMed 17441972Bevilaqua Grossi D, Lipton RB, Bigal ME. Temporomandibular disorders and migraine chronification. Curr Pain Headache Rep. 2009 Aug;13(4):314-8. doi: 10.1007/s11916-009-0050-9.
PubMed 19586596Goncalves DA, Camparis CM, Speciali JG, Franco AL, Castanharo SM, Bigal ME. Temporomandibular disorders are differentially associated with headache diagnoses: a controlled study. Clin J Pain. 2011 Sep;27(7):611-5. doi: 10.1097/AJP.0b013e31820e12f5.
PubMed 21368664Kamaleri Y, Natvig B, Ihlebaek CM, Bruusgaard D. Does the number of musculoskeletal pain sites predict work disability? A 14-year prospective study. Eur J Pain. 2009 Apr;13(4):426-30. doi: 10.1016/j.ejpain.2008.05.009. Epub 2008 Jul 2.
PubMed 18599328Justribo-Manion C, Padros-Auge J, Mesa-Jimenez J, Bara-Casaus J, Zuil-Escobar JC, Alvarez Bustins G. Assessment of chronic overlapping pain comorbidities for the management of temporomandibular disorders: Secondary analysis of a randomized clinical trial. Physiother Theory Pract. 2025 Jul;41(7):1339-1354. doi: 10.1080/09593985.2024.2419637. Epub 2024 Oct 28.
PubMed 39467222Dahan H, Shir Y, Velly A, Allison P. Specific and number of comorbidities are associated with increased levels of temporomandibular pain intensity and duration. J Headache Pain. 2015;16:528. doi: 10.1186/s10194-015-0528-2. Epub 2015 May 20.
PubMed 26002637Chen H, Slade G, Lim PF, Miller V, Maixner W, Diatchenko L. Relationship between temporomandibular disorders, widespread palpation tenderness, and multiple pain conditions: a case-control study. J Pain. 2012 Oct;13(10):1016-27. doi: 10.1016/j.jpain.2012.07.011.
PubMed 23031401Meng H, Dai J, Li Y. Quantitative sensory testing in patients with the muscle pain subtype of temporomandibular disorder: a systemic review and meta-analysis. Clin Oral Investig. 2021 Dec;25(12):6547-6559. doi: 10.1007/s00784-021-04171-5. Epub 2021 Sep 6.
PubMed 34487241Bevilaqua-Grossi D, Chaves TC, de Oliveira AS, Monteiro-Pedro V. Anamnestic index severity and signs and symptoms of TMD. Cranio. 2006 Apr;24(2):112-8. doi: 10.1179/crn.2006.018.
PubMed 16711273Almoznino G, Zini A, Zakuto A, Zlutzky H, Bekker S, Shay B, Haviv Y, Sharav Y, Benoliel R. Muscle tenderness score in temporomandibular disorders patients: A case-control study. J Oral Rehabil. 2019 Mar;46(3):209-218. doi: 10.1111/joor.12743. Epub 2018 Nov 20.
PubMed 30388315van Welie FC, Dahan A, van Velzen M, Terwindt GM. Pain profiling in migraine: a systematic review of Quantitative Sensory Testing (QST), Conditioned Pain Modulation (CPM), and Corneal Confocal Microscopy (CCM). J Headache Pain. 2024 Dec 19;25(1):224. doi: 10.1186/s10194-024-01932-x.
PubMed 39701963Castien R, Duineveld M, Maaskant J, De Hertogh W, Scholten-Peeters G. Pericranial Total Tenderness Score in Patients with Tension-type Headache and Migraine. A Systematic Review and Meta-analysis. Pain Physician. 2021 Dec;24(8):E1177-E1189.
PubMed 34793636Dibello V, Lozupone M, Sardone R, Ballini A, Lafornara D, Dibello A, Vertucci V, Santarcangelo F, Maiorano G, Stallone R, Petruzzi M, Daniele A, Solfrizzi V, Panza F. Temporomandibular Disorders as Contributors to Primary Headaches: A Systematic Review. J Oral Facial Pain Headache. 2023 Spring;37(2):91-100. doi: 10.11607/ofph.3345.
PubMed 37389836Conti PC, Costa YM, Goncalves DA, Svensson P. Headaches and myofascial temporomandibular disorders: overlapping entities, separate managements? J Oral Rehabil. 2016 Sep;43(9):702-15. doi: 10.1111/joor.12410. Epub 2016 May 18.
PubMed 27191928Alqutaibi AY, Alhammadi MS, Hamadallah HH, Altarjami AA, Malosh OT, Aloufi AM, Alkahtani LM, Alharbi FS, Halboub E, Almashraqi AA. Global prevalence of temporomandibular disorders: a systematic review and meta-analysis. J Oral Facial Pain Headache. 2025 Jun;39(2):48-65. doi: 10.22514/jofph.2025.025. Epub 2025 Jun 12.
PubMed 41070533
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pericranial and General Sensitivity in Patients With Primary Headache: a Multicenter Case-control Study
- ClinicalTrials.gov ID
- NCT07514208
- Acronym / sponsor ID
- HEAD-TMD / REST-ECL-2025-01
- Conditions
- Primary Headache Disorders, Tension Headache, Tension-type Headache, Migraine, Chronic Overlapping Pain Disorders
- Keywords
- Primary headache, Migraine, Tension-type headache, Temporomandibular disorders, Pericranial tenderness, Pressure pain threshold, Central sensitization, Chronic overlapping pain conditions
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Universitat Internacional de CatalunyaUniversity, hospital or other
- Study start
- 31 Mar 2026 (estimated)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 7 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary headaches such as migraine and tension type headache are among the most common neurological disorders and frequently cause significant disability and reduced quality of life. Increasing evidence suggests that these headaches may share biological mechanisms with temporomandibular disorders, a group of conditions affecting the jaw muscles and temporomandibular joint. Both conditions are also often associated with other chronic pain disorders, suggesting that altered pain processing and sensitization of the nervous system may play an important role in their development.
Despite these observations, few studies have simultaneously evaluated local muscle tenderness around the head and neck, generalized pain sensitivity in other parts of the body, and the presence of additional chronic pain conditions in patients with primary headaches. Understanding how these factors interact may help clarify why some patients develop more severe or persistent headache disorders and may improve future diagnostic and treatment strategies.
The aim of this multicenter observational study is to compare patients with primary headaches to healthy individuals without headaches. The study will assess sensitivity of muscles around the head and neck, general pain sensitivity at distant body sites, the presence of temporomandibular disorders, and the number of other chronic pain conditions. Participants will also complete questionnaires about pain symptoms and related health conditions.
Participants will undergo a clinical examination performed by trained clinicians, including manual assessment of tenderness in head and neck muscles and measurement of pressure pain thresholds using a handheld device. Additional evaluations will include standardized questionnaires about pain intensity, pain distribution, and symptoms related to central sensitization. Cervical motor and sensorimotor function will also be evaluated using a wearable sensor system.
By comparing individuals with primary headaches and healthy controls, the study aims to better understand the relationship between headache disorders, jaw related pain conditions, and general pain sensitivity. The results may contribute to improved clinical assessment and a more comprehensive understanding of the mechanisms underlying headache and related pain disorders.
Detailed description
Primary headaches are among the most prevalent neurological disorders worldwide and represent a major cause of disability and reduced quality of life. Migraine and tension type headache are the most common forms and are characterized by complex pathophysiological mechanisms involving peripheral and central nervous system processes. These mechanisms include altered nociceptive processing, dysfunction of endogenous pain modulation systems, neurovascular interactions, and neuroinflammatory responses.
Temporomandibular disorders are musculoskeletal conditions affecting the temporomandibular joint, masticatory muscles, and associated structures. Previous research has shown that temporomandibular disorders frequently coexist with primary headaches. Both conditions share anatomical and neurophysiological pathways through the trigeminal system, which may contribute to overlapping clinical manifestations and mutual influence between disorders. In addition, individuals with temporomandibular disorders or headaches often present with other chronic overlapping pain conditions such as low back pain, fibromyalgia, irritable bowel syndrome, or chronic fatigue syndrome. This broader pattern of comorbidity has been associated with altered pain sensitivity and central sensitization mechanisms.
Experimental and clinical studies have demonstrated that patients with primary headaches and temporomandibular disorders often exhibit increased tenderness of pericranial and cervical muscles as well as reduced pressure pain thresholds both locally and at distant anatomical sites. These findings suggest the presence of peripheral sensitization in local tissues together with generalized hypersensitivity reflecting central sensitization processes. However, previous studies have often assessed these mechanisms separately, have used heterogeneous methodologies, and have rarely evaluated headache disorders and temporomandibular disorders simultaneously using standardized diagnostic criteria.
The present study aims to address these limitations through a multicenter observational design conducted in Spain and Germany. The study will compare individuals diagnosed with primary headache to healthy control participants without clinically relevant headache symptoms. The primary objective is to evaluate differences in pericranial muscle tenderness and generalized pressure pain sensitivity between these groups. Additional objectives include exploring the association between the number of chronic overlapping pain conditions and measures of pain sensitization, and examining the coexistence between primary headaches and temporomandibular disorders.
Participants with primary headache will be diagnosed according to the International Classification of Headache Disorders third edition by headache specialists. Temporomandibular disorders will be assessed using the Diagnostic Criteria for Temporomandibular Disorders. Pain sensitivity will be evaluated through standardized manual palpation of pericranial muscles using the Total Tenderness Score and by measuring pressure pain thresholds at extra trigeminal anatomical sites with digital algometry. Additional clinical variables will include self reported pain intensity, pain distribution, and symptoms associated with central sensitization. Cervical motor and sensorimotor function will also be assessed using a wearable sensor based measurement system that records cervical movement patterns and proprioceptive performance during standardized tests.
By integrating clinical examination, quantitative sensory testing, and standardized questionnaires within the same protocol, the study aims to provide a comprehensive characterization of pain sensitivity and comorbidity patterns in patients with primary headache. The results may improve understanding of the relationship between headache disorders, temporomandibular disorders, and generalized pain sensitization, and may contribute to the development of more comprehensive diagnostic and therapeutic approaches for individuals with complex pain presentations.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Primary Headache | – | Diagnostic Test: Pericranial Tenderness Assessment, Diagnostic Test: Pressure Pain Threshold Assessment, Diagnostic Test: Temporomandibular Disorder Assessment, Diagnostic Test: Patient-Reported Outcome Assessment, Diagnostic Test: Cervical Function Assessment, Diagnostic Test: Multimodal Clinical AssessmentParticipants diagnosed with primary headache disorders according to the International Classification of Headache Disorders third edition. Diagnosis will be confirmed by a headache specialist. Participants may include individuals with migraine or tension type headache and will undergo standardized clinical assessment including evaluation of pericranial tenderness, pressure pain thresholds, temporomandibular disorders, and pain related questionnaires. |
| Healthy subjects | – | Diagnostic Test: Pericranial Tenderness Assessment, Diagnostic Test: Pressure Pain Threshold Assessment, Diagnostic Test: Temporomandibular Disorder Assessment, Diagnostic Test: Patient-Reported Outcome Assessment, Diagnostic Test: Cervical Function Assessment, Diagnostic Test: Multimodal Clinical AssessmentHealthy volunteers without clinically relevant headache after screening using a questionnaire based on the International Classification of Headache Disorders criteria. Participants who meet criteria for possible headache disorders will be excluded or referred for medical evaluation. Healthy controls will undergo the same clinical assessments as the case group to allow comparison of pain sensitivity and related clinical variables. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study population will consist of adults recruited from neurology and orofacial pain clinical settings as well as from the general population. Participants with primary headache disorders will be recruited through headache specialists and clinicians working in participating centers. Eligible patients must have a confirmed diagnosis of primary headache according to the International Classification of Headache Disorders third edition and be under stable medical treatment. Healthy control participants will be recruited from the community, including students and university staff, and will be screened using a structured questionnaire to exclude individuals with clinically relevant headache disorders. All participants will be adults able to understand the study procedures and provide informed consent. Recruitment will take place at clinical and academic centers in Spain and Germany.
Key inclusion criteria (5 listed)
- Adults diagnosed with primary headache disorders, including migraine or tension-type headache, according to the International Classification of Headache Disorders third edition.
- Diagnosis confirmed by a headache specialist.
- Stable medical treatment for headache for at least six months prior to participation.
- Ability to understand and communicate in Spanish, English, or German.
- Ability to provide written informed consent.
Key exclusion criteria (6 listed)
- Presence of secondary headache disorders or clinical suspicion of secondary headache based on screening criteria.
- Recent onset of undiagnosed headache or unilateral neck pain associated with neurological or neuropathic symptoms.
- Severe dermatological conditions or injuries affecting the head, neck, or intraoral region that could interfere with clinical examination.
- Recent fractures affecting the head or cervical region.
- Previous diagnosis of uncontrolled psychiatric disorders or neurodegenerative diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pericranial Tenderness AssessmentAlso: TTS, Pericranial Tenderness ExaminationPericranial tenderness will be assessed using the Total Tenderness Score, a standardized clinical examination based on manual palpation of pericranial and cervical muscles. Bilateral palpation will be performed on eight pairs of muscle bodies and insertions including the masseter, temporalis, frontal muscle, coronoid process, upper trapezius, sternocleidomastoid, suboccipital muscles, and mastoid process. Palpation will be applied with approximately 1 kg of pressure using the second and third fingertips rotated for four to five seconds. Participant responses will be rated using a four point scale ranging from 0 (no tenderness) to 3 (severe tenderness with withdrawal or pronounced facial reaction). The sum of all responses will generate the Total Tenderness Score, with a maximum possible score of 48. This assessment is commonly used to quantify pericranial muscle tenderness in patients with headache and temporomandibular disorders. | Diagnostic test | Healthy subjects, Primary Headache |
| Pressure Pain Threshold AssessmentAlso: PPT, Pressure Pain Threshold, Pressure AlgometryPressure pain thresholds will be assessed using a handheld digital algometer equipped with a 1 cm² probe. The probe will be positioned perpendicular to the skin at predefined extra trigeminal anatomical sites including the tibialis anterior muscle, the radial carpal extensor region at the dorsal wrist joint line, and the interspinous space between L5 and S1. Pressure will be progressively applied at a constant rate following visual guidance provided by the device interface. Participants will be instructed to indicate the moment when the sensation changes from pressure to pain. Three measurements will be obtained at each anatomical site with a resting interval between assessments. The mean value of the repeated measurements will be recorded and used to quantify generalized mechanical pain sensitivity. | Diagnostic test | Healthy subjects, Primary Headache |
| Temporomandibular Disorder AssessmentAlso: DC/TMD, Diagnostic Criteria for Temporomandibular DisordersPain related temporomandibular disorders will be assessed using the standardized Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) clinical protocol. The examination includes structured assessment of temporomandibular joint pain, masticatory muscle pain, mandibular movement, joint sounds, and pain during functional movements or palpation. Based on the DC/TMD diagnostic algorithms, participants will be classified into pain related temporomandibular disorder categories including arthralgia, myalgia, combined myalgia and arthralgia, or headache attributed to temporomandibular disorder. The examination will be performed by trained clinicians following the validated DC/TMD protocol. | Diagnostic test | Healthy subjects, Primary Headache |
| Patient-Reported Outcome AssessmentAlso: Self-Reported Questionnaires, Patient QuestionnairesParticipants will complete standardized self-reported questionnaires to assess pain related symptoms and associated health conditions. These will include the Central Sensitization Inventory to evaluate symptoms associated with central sensitization, the Brief Pain Inventory Short Form to assess pain intensity and pain related interference with daily activities, and a body pain drawing to document the distribution of pain. Additional questions will collect information on the presence and duration of physician-diagnosed chronic overlapping pain conditions. The questionnaires will be administered through a secure electronic data collection platform prior to or during the clinical assessment. | Diagnostic test | Healthy subjects, Primary Headache |
| Cervical Function AssessmentAlso: NeckCare Assessment, Cervical Range of Motion Assessment, Cervical Sensorimotor Function Test, Cervical function will be assessed using the NeckCare system, a wearable sensor-based platform designed to measure cervical spine kinematics and sensorimotor control. The system uses a lightweight heaCervical function will be assessed using the NeckCare system, a wearable sensor-based platform designed to measure cervical spine kinematics and sensorimotor control. The system uses a lightweight head-mounted sensor connected to a computer interface that records cervical movement in real time. Active cervical range of motion will be measured for flexion, extension, right and left rotation, and right and left lateral flexion. Cervical proprioception will be evaluated using the Joint Position Error test, in which participants attempt to reposition the head to a neutral position without visual feedback after performing active cervical movements. Sensorimotor control will also be assessed using the Butterfly Test, which requires participants to follow a moving visual target with head movements while the system quantifies movement accuracy, coordination, and smoothness. | Diagnostic test | Healthy subjects, Primary Headache |
| Multimodal Clinical AssessmentAlso: Comprehensive Pain Assessment, Multidimensional Clinical EvaluationParticipants will undergo a standardized multimodal clinical assessment designed to characterize pain sensitivity and related clinical variables. The assessment will include evaluation of pericranial muscle tenderness using the Total Tenderness Score, measurement of extra trigeminal pressure pain thresholds with digital algometry, and clinical examination for temporomandibular disorders using the Diagnostic Criteria for Temporomandibular Disorders protocol. Participants will also complete validated patient reported outcome measures assessing central sensitization symptoms, pain intensity, pain related interference, and distribution of pain. In addition, cervical spine function will be evaluated through objective measurement of cervical range of motion, proprioception, sensorimotor control, and cervical flexor muscle strength and endurance using wearable sensor technology and digital dynamometry. This integrated evaluation provides a comprehensive characterization of local and generaliz | Diagnostic test | Healthy subjects, Primary Headache |
Primary outcome
Total Pericranial Tenderness Score
Time frame: Baseline assessment during the study visit.
Pericranial tenderness will be quantified using the Total Tenderness Score obtained through standardized manual palpation of bilateral cranial and cervical muscles. Eight pairs of anatomical sites will be examined, and responses will be rated on a four point scale ranging from 0 (no tenderness) to 3 (severe tenderness with withdrawal or pronounced facial reaction). The total score ranges from 0 to 48, with higher values indicating greater pericranial muscle tenderness.
Extra-Trigeminal Pressure Pain Threshold
Time frame: Baseline assessment during the study visit.
Generalized pain sensitivity will be assessed through pressure pain threshold measurements using a handheld digital algometer at extra-trigeminal anatomical sites including the tibialis anterior muscle, the radial carpal extensor region, and the interspinous space between L5 and S1. Participants will indicate the point at which pressure becomes painful. Three measurements will be obtained at each site and the mean value will be used for analysis. Lower pressure pain threshold values indicate increased mechanical pain sensitivity.
5 secondary outcomes
Presence of pain related temporomandibular disorders according to DC/TMD
Time frame: Baseline assessment during the study visit.
Central Sensitization Inventory Score
Time frame: Baseline assessment during the study visit.
Central Sensitization Related Comorbid Conditions
Time frame: Baseline assessment during the study visit.
Pain Intensity and Pain Interference
Time frame: Baseline assessment during the study visit.
Pain Distribution
Time frame: Baseline assessment during the study visit.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
- Background: PubMed 17441972Glaros AG, Urban D, Locke J. Headache and temporomandibular disorders: evidence for diagnostic and behavioural overlap. Cephalalgia. 2007 Jun;27(6):542-9. doi: 10.1111/j.1468-2982.2007.01325.x. Epub 2007 Apr 18.
- Background: PubMed 19586596Bevilaqua Grossi D, Lipton RB, Bigal ME. Temporomandibular disorders and migraine chronification. Curr Pain Headache Rep. 2009 Aug;13(4):314-8. doi: 10.1007/s11916-009-0050-9.
- Background: PubMed 21368664Goncalves DA, Camparis CM, Speciali JG, Franco AL, Castanharo SM, Bigal ME. Temporomandibular disorders are differentially associated with headache diagnoses: a controlled study. Clin J Pain. 2011 Sep;27(7):611-5. doi: 10.1097/AJP.0b013e31820e12f5.
- Background: PubMed 18599328Kamaleri Y, Natvig B, Ihlebaek CM, Bruusgaard D. Does the number of musculoskeletal pain sites predict work disability? A 14-year prospective study. Eur J Pain. 2009 Apr;13(4):426-30. doi: 10.1016/j.ejpain.2008.05.009. Epub 2008 Jul 2.
- Background: PubMed 39467222Justribo-Manion C, Padros-Auge J, Mesa-Jimenez J, Bara-Casaus J, Zuil-Escobar JC, Alvarez Bustins G. Assessment of chronic overlapping pain comorbidities for the management of temporomandibular disorders: Secondary analysis of a randomized clinical trial. Physiother Theory Pract. 2025 Jul;41(7):1339-1354. doi: 10.1080/09593985.2024.2419637. Epub 2024 Oct 28.
- Background: PubMed 26002637Dahan H, Shir Y, Velly A, Allison P. Specific and number of comorbidities are associated with increased levels of temporomandibular pain intensity and duration. J Headache Pain. 2015;16:528. doi: 10.1186/s10194-015-0528-2. Epub 2015 May 20.
- Background: PubMed 23031401Chen H, Slade G, Lim PF, Miller V, Maixner W, Diatchenko L. Relationship between temporomandibular disorders, widespread palpation tenderness, and multiple pain conditions: a case-control study. J Pain. 2012 Oct;13(10):1016-27. doi: 10.1016/j.jpain.2012.07.011.
- Background: PubMed 34487241Meng H, Dai J, Li Y. Quantitative sensory testing in patients with the muscle pain subtype of temporomandibular disorder: a systemic review and meta-analysis. Clin Oral Investig. 2021 Dec;25(12):6547-6559. doi: 10.1007/s00784-021-04171-5. Epub 2021 Sep 6.
- Background: PubMed 16711273Bevilaqua-Grossi D, Chaves TC, de Oliveira AS, Monteiro-Pedro V. Anamnestic index severity and signs and symptoms of TMD. Cranio. 2006 Apr;24(2):112-8. doi: 10.1179/crn.2006.018.
- Background: PubMed 30388315Almoznino G, Zini A, Zakuto A, Zlutzky H, Bekker S, Shay B, Haviv Y, Sharav Y, Benoliel R. Muscle tenderness score in temporomandibular disorders patients: A case-control study. J Oral Rehabil. 2019 Mar;46(3):209-218. doi: 10.1111/joor.12743. Epub 2018 Nov 20.
- Background: PubMed 39701963van Welie FC, Dahan A, van Velzen M, Terwindt GM. Pain profiling in migraine: a systematic review of Quantitative Sensory Testing (QST), Conditioned Pain Modulation (CPM), and Corneal Confocal Microscopy (CCM). J Headache Pain. 2024 Dec 19;25(1):224. doi: 10.1186/s10194-024-01932-x.
- Background: PubMed 34793636Castien R, Duineveld M, Maaskant J, De Hertogh W, Scholten-Peeters G. Pericranial Total Tenderness Score in Patients with Tension-type Headache and Migraine. A Systematic Review and Meta-analysis. Pain Physician. 2021 Dec;24(8):E1177-E1189.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Headache Disorders and Tension Headache, run by Universitat Internacional de Catalunya at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Pericranial Tenderness Score (time frame: Baseline assessment during the study visit.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07514208, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.