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NCT Number: NCT06813040

Efficacy of Repetitive Transcranial Magnetic Stimulation in Temporomandibular Disorders.

Temporomandibular disorder (TMD) refers to a group of musculoskeletal conditions that affect the temporomandibular joint (TMJ), the masticatory muscles, and the associated structures. It is assumed that 30 to 40% of cases of acute painful TMD becomes chronic. Chronic pain is a significant public health problem, affecting professional and social activities, emotional state, and quality of life. The pathophysiological mechanisms involved in chronic orofacial pain are complex and multifaceted and not yet fully understood. The coexistence of psychological factors associated with vast peripheral and central mechanisms makes chronic orofacial pain treatment a complex challenge. Due to the complexity of chronic TMDs, some patients remain refractory to current therapeutic methods. Thus, several efforts have been made to develop therapies aimed at the treatment of neuroplastic changes induced by chronic pain. In this sense, transcranial stimulation methods appear to be a promising technique. Transcranial Magnetic Stimulation (TMS) is a non-invasive, safe, and approved treatment for clinical use in psychiatric disorders such as depression and chronic pain. Given the above, it is necessary to develop studies to investigate the TMS effectiveness in chronic TMD. This study aims to evaluate the effectiveness of transcranial magnetic stimulation in patients with chronic temporomandibular disorders. An additional objective is to determine possible predictors for treatment success based on the assessment of functional brain connectivity and psychosocial characteristics.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Coimbra

Coimbra, 3000-548, Portugal

Location status: Recruiting

About this study

Temporomandibular disorder (TMD) is a generic term used to describe musculoskeletal disorders that affect the temporomandibular joint (TMJ), masticatory muscles, and related structures. TMD comprises two main groups: intra-articular TMD and masticatory muscle disorders. It is noteworthy that each of these groups still contains different diagnoses. Furthermore, masticatory muscle disorders and intra-articular TMD often coexist in the same individual. Such characteristics contribute to the complex diagnosis and treatment of TMDs.

It is estimated that TMD affects 5 to 12% of the population and is considered the second most prevalent musculoskeletal disorder, behind only chronic low back pain. Pain, joint noises, and limitation of mandibular movements are the main signs and symptoms of TMD. TMJ noises and limited jaw movements are often associated with intra-articular TMD. On the other hand, pain is a common symptom in different types of TMD, and it can be localized or diffuse and even as otalgia or headache. It is assumed that 30 to 40% of cases of acute painful TMD becomes chronic. Chronic pain impacts professional and social activities, emotional state, and quality of life. The pathophysiological mechanisms of chronic orofacial pain are complex and multifaceted, and not yet fully understood. In addition, the coexistence of psychological factors associated with the vast number of peripheral and central mechanisms (for example, functional and structural neuroplasticity and, more specifically, peripheral and central sensitization) makes the treatment of chronic orofacial pain a challenge extremely complex.

TMD treatment comprises a wide range of therapeutic modalities. Conservative treatments constitute the first therapeutic option, aiming to reduce joint and muscle overload, control local inflammatory factors, and reduce some risk factors, such as waking bruxism and psychological disorders. However, due to the complexity of chronic TMDs, some patients remain refractory to current therapeutic methods. Thus, several efforts have been made to develop therapies to treat neuroplastic changes associated with chronic pain. In this regard, transcranial stimulation methods appear to be a promising treatment. Transcranial Magnetic Stimulation (TMS) is a non-invasive, safe, and approved method for clinical use in psychiatric disorders and chronic pain. Recent scientific evidence has demonstrated that high-frequency TMS when applied to the motor cortex (M1), presents short-term effectiveness in reducing chronic pain and improving quality of life. A systematic review conducted by Ferreira demonstrated promising results of TMS in orofacial pain.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Individuals of both sexes, literate, aged over 18 years with the diagnosis of muscular and/or joint TMD by the Diagnostic Criteria for Temporomandibular Disorders (DC-TMD).
  • Pain duration longer than 6 months.
  • Intensity of orofacial pain greater than 5 on the visual analogue scale (VAS).

Exclusion criteria

  • Volunteers who present verbal communication impairment due to a neurological disorder, a sequel to a previous illness, or a psychiatric condition.
  • Pregnant women
  • Individuals with any impediment to MRI: having a pacemaker or implantable defibrillator, cochlear implant, ferromagnetic aneurysm clips, electrodes used for deep brain stimulation, ocular implants, Swan-Ganz catheter, orthopedic prostheses or metallic bodies close to the area of interest.
  • Individuals with any contraindication for transcranial magnetic stimulation: have focal or generalized encephalopathies, increased intracranial pressure, and severe heart disease; history of head trauma, epilepsy, and individuals with first-degree relatives diagnosed with idiopathic epilepsy; use of drugs that lower the seizure threshold (tricyclic antidepressants and antipsychotics); chronic use of alcohol or epileptogenic drugs.

Treatment and study plan

Active rTMS

Device

Repetitive TMS will be applied at 10Hz on the motor cortex. The protocol consists of 2000 pulses per session and an intensity of 90% of the resting motor threshold. There will be 10 sessions with a minimum interval of 24 hours and a maximum of 72 hours. A figure-8 coil will be used.

sham rTMS

Device

The sham TMS will have the same visual and sound characteristics, but without the passage of the magnetic field to the scalp.

Primary outcomes

  1. Pain intensity

    Time frame: Primary outcomes will be assessed before and after all TMS sessions. Follow-up will be carried out one week, two weeks, and 1 month after treatment.

    Visual Analogue Scale Visual Analogue Scale ranges from 0 to 10 and consists of a 100 mm horizontal line. The left end is labeled 'No pain,' while the right end is marked 'Worst pain imaginable

  2. Functional limitation

    Time frame: Primary outcomes will be assessed before and after all TMS sessions. Follow-up will be carried out one week, two weeks, and 1 month after treatment.

    Visual Analogue Scale The Visual Analogue Scale (VAS) ranges from 0 to 10 and consists of a 100 mm horizontal line. The left end is labeled 'No functional limitation,' while the right end is marked 'Worst functional limitation imaginable.

Secondary outcomes

  1. Disability associated with pain

    Time frame: Change from baseline to mid-treatment, immediately after the last simulated or active TMS session, and follow-up will be carried out one week, 15 days and 1 month after the end of treatment.

    Graded Chronic Pain Scale version 2.0

  2. Depression

    Time frame: Change from baseline to mid-treatment, immediately after the last simulated or active TMS session, and follow-up will be carried out one week, 15 days and 1 month after the end of treatment.

    Patient Health Questionnaire - PQ-9;

  3. Anxiety

    Time frame: Change from baseline to mid-treatment, immediately after the last simulated or active TMS session, and follow-up will be carried out one week, 15 days and 1 month after the end of treatment.

    Generalized Anxiety Disorder 7 - GAD-7

  4. Central sensitization

    Time frame: hange from baseline to mid-treatment, immediately after the last simulated or active TMS session, and follow-up will be carried out one week, 15 days and 1 month after the end of treatment.

    Central Sensitization Inventory

  5. Quality of Life

    Time frame: Change from baseline to mid-treatment, immediately after the last simulated or active TMS session, and follow-up will be carried out one week, 15 days and 1 month after the end of treatment.

    World Health Organization Quality of Life Assessment Tool - WHOQOL The WHOQOL-BREF instrument assesses the quality of life across four domains: physical, psychological, social relationships, and environment. The questionnaire provides a score for each domain, as well as an overall score derived from all domains. All scores follow a positive, increasing order, with higher scores indicating a better quality of life.

  6. Functional connectivity

    Time frame: Change from baseline to one week after the end of treatment.

    Functional magnetic resonance imaging (fMRI)

Study contacts

Contact information is provided by the study sponsor or research team.

Catarina Duarte

CONTACT

[email protected]

+351 239 488510

Miguel Castelo-Branco

CONTACT

[email protected]

+351 239 488510

Sponsors and collaborators

Lead sponsor

University of Coimbra

Other

Registry information

Official study title

Efficacy of Repetitive Transcranial Magnetic Stimulation in Chronic Pain in Patients with Temporomandibular Disorders.

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Feb 6, 2025
Registry last updated
Feb 13, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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