Neuro-modulation of Central Pain Pathways in Non Inflammatory Musculoskeletal Pain Syndrome

Overview

The aim of this clinical trial is to see if transcranial electrical stimulation (tES) can help reduce pain and improve quality of life in children and adolescents (ages 10-21, both sexes) with juvenile fibromyalgia or other non-inflammatory musculoskeletal pain syndromes. The main questions are whether active tES works better than sham (placebo) stimulation for pain relief and whether it leads to measurable changes in brain activity.Participants will be randomly assigned to receive either active or sham tES for 20 minutes a day over two weeks. They'll complete questionnaires about their pain and quality of life, do some simple physical and motor tests, and undergo non-invasive brain measurements before and after the intervention. The results will help understand if tES is a safe and effective option for managing chronic pain in young people. Specific Aims: Aim 1a. transcranial stimulation will be associated with significant improvements in pain and functioning (e.g., 30% or greater symptom relief or 20% or greater improvement in QoL) Aim 1b. For each tES condition, estimate mean changes in motor evoked potential (MEP) amplitudes induced by TMS stimulation. Aim 2. Compare the tES conditions (Active, Sham) in terms of the mean changes in MEP amplitude. Aim 3. Obtain statistical estimates of variance components needed for the planning of a future study. Therefore, we hypothesize that anodal tES stimulation decreases MEP amplitudes compared to sham tES condition. We further hypothesize that MEP amplitudes are positively correlated. This study will be the first randomized, double-blind, controlled study of tES technology in children as an adjunctive pain management strategy for MPS. Data from this trial will likely yield information regarding the feasibility and efficacy of tES as a chronic pain-management approach.

This clinical trial investigates the efficacy and safety of transcranial electrical stimulation (tES) as a non-pharmacological intervention for pain management in pediatric patients (ages 10-21, both sexes) with juvenile fibromyalgia (JFM) and other non-inflammatory musculoskeletal pain syndromes (MPS). These conditions are characterized by chronic, widespread musculoskeletal pain, fatigue, sleep disturbances, cognitive and psychological symptoms, and significantly reduced quality of life. Current management strategies are multidisciplinary, but there is no gold standard treatment, especially for pediatric patients.The study is a 24-month, open-label, randomized, actively controlled, mono-center, prospective, superiority trial. Forty-six participants will be randomly assigned to one of two arms: Active tES or Sham tES. The primary aim is to determine whether active tES leads to significant improvements in pain (≥30% reduction) and quality of life (≥20% improvement) compared to sham stimulation. Secondary aims include evaluating changes in neurophysiological markers (such as motor evoked potentials, MEPs) and functional outcomes.Participants will undergo a comprehensive assessment including behavioral, neurophysiological, and patient-reported outcome measures. Behavioral assessments include quality of life questionnaires (J-FiMAR), physical and motor function tests (6-Minute Walking Test, Shuttle Run, Sit-up, Long Jump, Flamingo Balance Test, Functional Mobility Scale), and patient-reported outcomes (pain, fatigue, sleep, mood). Neurophysiological assessments involve transcranial magnetic stimulation (TMS) and electromyography (EMG) to measure cortical excitability and MEPs before and after the intervention.The intervention consists of 10 consecutive daily sessions (over 2 weeks) of either active or sham tES. Active tES is delivered for 20 minutes per session, with the anodal electrode placed over the left primary motor cortex (C3, 10-20 EEG system) and the reference electrode over the contralateral supraorbital region. Sham tES mimics the initial sensation of stimulation but does not deliver active current after the first minute. Both protocols use CE-certified, pediatric-appropriate equipment and follow international safety guidelines.Randomization is performed using random permuted blocks via Random.org to ensure balanced group allocation. The study includes interim analysis after 50% enrollment. Data analysis will use appropriate statistical methods (t-tests, ANOVA, non-parametric tests, Bonferroni correction) to compare outcomes between groups and assess effect sizes.Risks associated with tES and TMS are minimal, with the most common adverse effects being mild and transient (e.g., headache, tingling). Strict inclusion/exclusion criteria and continuous monitoring ensure participant safety. Ethical conduct is maintained according to international guidelines, with informed consent/assent required from all participants and their guardians.The results of this trial will provide valuable evidence on the feasibility, safety, and effectiveness of tES as a pain management strategy in young people with JFM and related conditions. The study also aims to identify objective neurophysiological and functional markers that could guide future personalized interventions and improve quality of life for affected patients.