Efficacy of Repetitive Transcranial Magnetic Stimulation in Temporomandibular Disorders.

Official title

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

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

• 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.]
• 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.]

Secondary outcome measures (6)

• 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.]
• 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.]
• 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.]
• 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.]
• 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.]
• Functional connectivity [Time frame: Change from baseline to one week after the end of treatment.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Portugal · 1 center

• University of Coimbra — Coimbra

Publications

• Okeson JP, de Leeuw R. Differential diagnosis of temporomandibular disorders and other orofacial pain disorders. Dent Clin North Am. 2011 Jan;55(1):105-20. doi: 10.1016/j.cden.2010.08.007. PMID 21094721
• Schiffman E, Ohrbach R, Truelove E, Look J, Anderson G, Goulet JP, List T, Svensson P, Gonzalez Y, Lobbezoo F, Michelotti A, Brooks SL, Ceusters W, Drangsholt M, Ettlin D, Gaul C, Goldberg LJ, Haythornthwaite JA, Hollender L, Jensen R, John MT, De Laat A, de Leeuw R, Maixner W, van der Meulen M, Murray GM, Nixdorf DR, Palla S, Petersson A, Pionchon P, Smith B, Visscher CM, Zakrzewska J, Dworkin SF PMID 24482784
• Lovgren A, Haggman-Henrikson B, Visscher CM, Lobbezoo F, Marklund S, Wanman A. Temporomandibular pain and jaw dysfunction at different ages covering the lifespan--A population based study. Eur J Pain. 2016 Apr;20(4):532-40. doi: 10.1002/ejp.755. Epub 2015 Aug 27. PMID 26311138
• Rammelsberg P, LeResche L, Dworkin S, Mancl L. Longitudinal outcome of temporomandibular disorders: a 5-year epidemiologic study of muscle disorders defined by research diagnostic criteria for temporomandibular disorders. J Orofac Pain. 2003 Winter;17(1):9-20. PMID 12756926
• Cohen SP, Mao J. Neuropathic pain: mechanisms and their clinical implications. BMJ. 2014 Feb 5;348:f7656. doi: 10.1136/bmj.f7656. PMID 24500412
• Yin Y, He S, Xu J, You W, Li Q, Long J, Luo L, Kemp GJ, Sweeney JA, Li F, Chen S, Gong Q. The neuro-pathophysiology of temporomandibular disorders-related pain: a systematic review of structural and functional MRI studies. J Headache Pain. 2020 Jun 19;21(1):78. doi: 10.1186/s10194-020-01131-4. PMID 32560622
• de Souza RF, Lovato da Silva CH, Nasser M, Fedorowicz Z, Al-Muharraqi MA. Interventions for the management of temporomandibular joint osteoarthritis. Cochrane Database Syst Rev. 2012 Apr 18;2012(4):CD007261. doi: 10.1002/14651858.CD007261.pub2. PMID 22513948
• Greene CS, Manfredini D. Transitioning to chronic temporomandibular disorder pain: A combination of patient vulnerabilities and iatrogenesis. J Oral Rehabil. 2021 Sep;48(9):1077-1088. doi: 10.1111/joor.13180. Epub 2021 Jun 3. PMID 33966303

Identifiers

NCT: NCT06813040 · ICNAS-FM-10,2022

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗