Evaluation of the Efficacy of Neuromodulation in the Control of Chronic Orofacial Pain

Официальное название

Evaluation of the Efficacy of Neuromodulation in the Control of Chronic Orofacial Pain: A Randomized Controlled Trial

Обзор

Chronic orofacial pain significantly affects patients' quality of life, compromising essential functions such as chewing and speech. Although conventional treatments are available, many patients do not achieve adequate and lasting relief. This project investigates the effectiveness of neuromodulation techniques, namely transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), as innovative therapeutic alternatives for the control of chronic orofacial pain. The study will be conducted in adult patients diagnosed with orofacial pain. Participants will be divided into two groups: one group will receive active neuromodulation (tDCS or TMS) and the other a sham treatment (placebo). Sessions will take place daily over two weeks. Assessments will include pain intensity, pain pressure threshold, masticatory function, and bite strength, in order to observe any functional changes. The group undergoing neuromodulation is expected to show a significant reduction in pain levels and improvements in quality of life compared to the placebo group. This study could support the adoption of neuromodulation as a complementary approach in the treatment of chronic orofacial pain, offering an effective and non-invasive alternative for patients who do not respond to conventional treatments.

Подробное описание

The study will be conducted at the University Clinic of the Egas Moniz School of Health and Science - Department of Orofacial Pain. The objective is to evaluate the effects of electrical and magnetic neuromodulation on different chronic pain conditions using standardized non-invasive brain stimulation protocols and validated clinical and functional assessment instruments.

Sample

Individuals with chronic low back pain (score between 40 and 80 on the Portuguese version of the Oswestry Disability Index) and chronic orofacial pain (score between 40 and 80 on the Portuguese version of the Manchester Orofacial Pain Disability Scale) will be selected.

For each chronic pain condition, 50 individuals will be enrolled and allocated into two groups: a control group and an intervention group.

Inclusion Criteria

Age between 18 and 75 years.

Diagnosis of chronic orofacial pain lasting longer than 3 months, confirmed by validated diagnostic criteria such as DC/TMD.

Initial Visual Analogue Scale (VAS) score ≥ 4.

Previous attempt of at least one conventional treatment with limited effectiveness.

Cognitive capacity sufficient to understand study procedures and provide informed consent.

Stable chronic pain medication regimen for at least four weeks prior to the intervention.

Exclusion Criteria

History of epilepsy, seizures, or other neurological conditions that contraindicate tDCS or TMS.

Presence of implanted medical devices, including pacemakers, cochlear implants, or other electronic/metallic devices in the head or neck region.

Pregnancy or breastfeeding.

Severe psychiatric disorders that may compromise adherence to study procedures.

Current or recent history (within the last six months) of alcohol or substance abuse.

Active infections or untreated systemic diseases that may interfere with the intervention or outcomes.

History of temporomandibular joint surgery or recent invasive dental procedures (within the last three months).

Known contraindications to TMS or tDCS, including intolerance to neuromodulation.

Participation in another clinical trial within the last three months.

Randomization

Participants will be randomly allocated to the control or intervention group by an independent investigator using an electronic randomization tool (Research Randomizer). Allocation will remain concealed until completion of assessments.

Sample Size Calculation

Sample size estimation indicates the need for 15 participants per group to ensure a statistical power of 85% (β = 0.20) and a significance level of p \< 0.05. The final sample size was expanded to enhance the robustness of statistical analyses and to compensate for potential dropouts.

Assessment Instruments Visual Analogue Scale (VAS)

A 0-10 numerical scale used to quantify pain intensity, where 0 indicates no pain and 10 represents the worst imaginable pain.

Brief Pain Inventory (BPI)

A multidimensional tool that assesses pain intensity and pain interference with daily activities over the past 24 hours.

Graded Chronic Pain Scale (GCPS)

A scale that classifies chronic pain into severity grades based on pain intensity and functional disability.

SF-36 Health Survey

A generic quality-of-life questionnaire comprising 36 items distributed across eight domains, with scores ranging from 0 (worst health status) to 100 (best health status).

Manchester Orofacial Pain Disability Scale

An instrument that measures functional disability associated with orofacial pain, focusing on daily activities such as chewing and speaking.

Pressure Pain Threshold (PPT)

Assessed using a portable algometer. The minimum pressure that elicits a painful sensation will be recorded. Each site will be measured twice, and the mean value will be used for analysis.

Intervention Transcranial Direct Current Stimulation (tDCS)

tDCS will be administered using 35 cm² electrodes for 20 minutes across five consecutive days. The anode will be positioned at C3 or C4, contralateral to the primary site of pain, according to the international 10-20 EEG system. The control group will receive sham stimulation with identical electrode placement and procedures.

Transcranial Magnetic Stimulation (TMS)

Вмешательства

• Устройство Active Neuromodulation (tDCS or TMS)
  Participants receive active non-invasive neuromodulation using either transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS). For tDCS, stimulation is delivered with 35 cm² electrodes, 1-2 mA, for 20 minutes, with the anode placed over C3 or C4 contralateral to the pain side, for five consecutive sessions. For TMS, stimulation is delivered with a figure-of-eight coil targeting the motor cortex corresponding to the orofacial region, following established safet
• Устройство Sham Neuromodulation (tDCS or TMS)
  Participants receive sham stimulation designed to mimic the sensory experience of tDCS or TMS without producing physiological neuromodulatory effects. For tDCS, the device uses brief ramp-up/ramp-down currents to simulate tingling without active stimulation. For TMS, a sham coil or angled coil is used to reproduce acoustic and scalp sensations while preventing magnetic induction. Session duration, procedures, and interaction with the operator are identical to the active arm to maintain blindi

Первичные конечные точки

• Pain Intensity Assessed by Visual Analogue Scale (VAS) [Срок оценки: Baseline, at the end of the 2-week intervention period (after 10 sessions), and 1 month after completion of the intervention]

Вторичные конечные точки (5)

• Pain Interference Measured by the Brief Pain Inventory (BPI) [Срок оценки: Baseline, at the end of the 2-week intervention period (after 10 sessions), and 1 month after completion of the intervention]
• Chronic Pain Severity Assessed by the Graded Chronic Pain Scale (GCPS) [Срок оценки: Baseline, at the end of the 2-week intervention period (after 10 sessions), and 1 month after completion of the intervention]
• Health-Related Quality of Life Measured by SF-36 [Срок оценки: Baseline, at the end of the 2-week intervention period (after 10 sessions), and 1 month after completion of the intervention]
• Pressure Pain Threshold (PPT) [Срок оценки: Baseline, at the end of the 2-week intervention period (after 10 sessions), and 1 month after completion of the intervention]
• Orofacial Functional Disability Assessed by the Manchester Orofacial Pain Disability Scale (MOPDS) [Срок оценки: Baseline, at the end of the 2-week intervention period (after 10 sessions), and 1 month after completion of the intervention]

Критерии участия

Критерии включения

• Age: Participants between 18 and 75 years old.
• Diagnosis of Chronic Orofacial Pain: Patients with persistent orofacial pain for more than 3 months, confirmed using DC/TMD or other validated diagnostic criteria.
• Pain Intensity: Baseline score on the Visual Analogue Scale (VAS) ≥ 4 (moderate to severe pain).
• Treatment History: Patients who have previously tried at least one conventional treatment (e.g., medication or physiotherapy) with limited or no success.
• Cognitive Ability: Participants cognitively able to understand the study procedures and provide informed consent.
• Stable Medication Regimen: Stable chronic pain medication for at least four weeks prior to the intervention.

Критерии исключения

• Neurological Disorders: History of epilepsy, seizures, or other neurological disorders that contraindicate TMS or tDCS.
• Implanted Medical Devices: Presence of pacemakers, cochlear implants, or other electronic/metallic devices in the head or neck region.
• Pregnancy: Pregnant or breastfeeding individuals, due to potential risks.
• Psychiatric Disorders: Severe psychiatric disorders (e.g., schizophrenia, unstable major depression) that may interfere with study adherence.
• Substance Abuse: Current or recent history (within the last 6 months) of alcohol or substance abuse.
• Active Medical Conditions: Active infections or untreated systemic diseases that may interfere with results.
• TMJ Surgery: History of recent temporomandibular joint surgery or invasive dental procedures (within the last 3 months).
• Contraindications for TMS/tDCS: Sensitivity, intolerance, or inability to tolerate the neuromodulation device.
• Participation in Another Study: Simultaneous or recent (within the last 3 months) participation in another clinical trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Португалия · 1 центр

• Egas Moniz School of Health and Science — Almada

Публикации

• Fricova J, Englerova K, Rokyta R. Noninvasive transcranial direct current stimulation (tDCS) for the treatment of orofacial pain. Neuro Endocrinol Lett. 2016 Oct;37(5):368-372. PMID 28231681
• Fricova J, Rokyta R. Transcranial Neurostimulation (rTMS, tDCS) in the Treatment of Chronic Orofacial Pain. Prog Neurol Surg. 2020;35:125-132. doi: 10.1159/000511134. Epub 2020 Oct 12. PMID 33045706
• Mayor RS, Ferreira NR, Lanzaro C, Castelo-Branco M, Valentim A, Donato H, Lapa T. Noninvasive transcranial brain stimulation in central post-stroke pain: A systematic review. Scand J Pain. 2024 Jul 3;24(1). doi: 10.1515/sjpain-2023-0130. eCollection 2024 Jan 1. PMID 38956966
• Ferreira NR, Junqueira YN, Correa NB, Fonseca EO, Brito NBM, Menezes TA, Magini M, Fidalgo TKS, Ferreira DMTP, de Lima RL, Carvalho AC, DosSantos MF. The efficacy of transcranial direct current stimulation and transcranial magnetic stimulation for chronic orofacial pain: A systematic review. PLoS One. 2019 Aug 15;14(8):e0221110. doi: 10.1371/journal.pone.0221110. eCollection 2019. PMID 31415654
• Herrero Babiloni A, Guay S, Nixdorf DR, de Beaumont L, Lavigne G. Non-invasive brain stimulation in chronic orofacial pain: a systematic review. J Pain Res. 2018 Aug 1;11:1445-1457. doi: 10.2147/JPR.S168705. eCollection 2018. PMID 30122975
• Knotkova H, Hamani C, Sivanesan E, Le Beuffe MFE, Moon JY, Cohen SP, Huntoon MA. Neuromodulation for chronic pain. Lancet. 2021 May 29;397(10289):2111-2124. doi: 10.1016/S0140-6736(21)00794-7. PMID 34062145

Идентификаторы

NCT: NCT07352384 · CEEM1660

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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