NCT07514208

Pericranial and General Sensitivity in Patients With Primary Headache

Pericranial and General Sensitivity in Patients With Primary Headache: a Multicenter Case-control Study

• Status: Enrolling By Invitation
• Phase: —
• Study type: Observational
• Enrollment: 120 (estimated)
• Sponsor: Universitat Internacional de Catalunya · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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. 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.

Conditions

• Primary Headache Disorders
• Tension Headache
• Tension-type Headache
• Migraine
• Chronic Overlapping Pain Disorders

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Pericranial Tenderness Assessment	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.
DIAGNOSTIC_TEST	Pressure Pain Threshold Assessment	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.
DIAGNOSTIC_TEST	Temporomandibular Disorder Assessment	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.
DIAGNOSTIC_TEST	Patient-Reported Outcome Assessment	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.
DIAGNOSTIC_TEST	Cervical Function Assessment	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.
DIAGNOSTIC_TEST	Multimodal Clinical Assessment	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

Timeline

• Start date: 2026-03-31
• Primary completion: 2027-06-01
• Completion: 2027-06-01
• First posted: 2026-04-07
• Last updated: 2026-04-07

Locations

1 site across 1 country: Spain