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Abstract
Introduction Chronic low back pain may be associated with pathoanatomical, neurophysiological, physical, psychological and social factors; thus, treatments to reduce symptoms are important to improve the quality of life of this population. We aimed to evaluate the effects of transcranial direct current stimulation (tDCS) combined with Pilates-based exercises compared with sham stimulation on pain, quality of life and disability in patients with chronic non-specific low back pain.
Methods and analysis This is a protocol for a double-blind randomised controlled trial with participants, outcome assessor and statistician blinded. We will include 36 individuals with a history of non-specific chronic low back pain for more than 12 weeks and minimum pain intensity of 3 points on the Numerical Pain Rating Scale. Individuals will be randomised into two groups: (1) active tDCS combined with Pilates-based exercises and (2) sham tDCS combined with Pilates-based exercises. Three weekly sessions of the protocol will be provided for 4 weeks, and individuals will be submitted to three assessments: the first (T0) will be performed before the intervention protocol, the second (T1) immediately after the intervention protocol and the third (T2) will be a follow-up 1 month after the end of the intervention. We will assess pain, disability, central sensitisation, quality of life, pressure pain threshold, global impression of change, adverse events and medication use. The Numerical Pain Rating Scale and the Roland-Morris Disability Questionnaire will be used at T1 to assess pain and disability, respectively, as primary outcome measures.
Ethics and dissemination This trial was prospectively registered in ClinicalTrials.gov website and ethically approved by the Ethics and Research Committee of the Faculty of Health Sciences of Trairi (report number: 5.411.244) before data collection. We will publish the results in a peer-reviewed medical journal and on institution websites.
Trial registration number ClinicalTrials.gov (NCT05467566).
- Chronic Pain
- Back pain
- Spine
- PAIN MANAGEMENT
- Physical Therapy Modalities
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STRENGTHS AND LIMITATIONS OF THIS STUDY
Robust randomised controlled trial design: the study employs a prospective, two-arm, double-blind randomised controlled trial design, considered a gold standard for evaluating treatment effects.
Adherence to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 recommendations: the trial protocol was developed according to the SPIRIT 2013 checklist, ensuring a comprehensive and standardised approach to study design and reporting.
Comprehensive outcome measures: the study incorporates a range of validated measures enhancing the comprehensiveness of the study findings.
Results’ generalisability: the specific population, with strict exclusion criteria, may limit the generalisability of the study findings to a broader population.
Single-centre setting: conducting the study in a single centre could potentially introduce site-specific biases and limit the external validity of the results.
Introduction
Low back pain affects a large part of the population and has been associated with disability, absence from work and socioeconomic impacts.1–3 Although most individuals recover within the first 3–6 months, a small portion continues to develop pain, leading to chronic low back pain.4 Several clinical conditions result in low back pain, but most cases have no defined cause and are classified as non-specific.5 Furthermore, even defined diagnoses may often be questioned since the source of pain may include a combination of several factors, such as pathoanatomical, neurophysiological, physical, psychological and social.6 7
In recent years, great attention has been given to the role of the central nervous system in chronic pain. Growing evidence associates chronic pain with significant changes in the central nervous system function, including central sensitisation and changes in structure and function of brain areas that control the perceived amount of pain.8–10 Therefore, new therapeutic strategies to treat pain using brain modulation have also been increasingly studied.11
Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates neuronal excitability in the brain by applying low-intensity direct current using electrodes placed in brain areas associated with pain processing.12–14 tDCS modifies brain activity by increasing or decreasing the excitability of neurons positioned between the anode and cathode electrodes.13–16 The electrode placement is one of the factors that can influence pain neuromodulation. The anodic electrode is usually positioned at M1, preferably in the hemisphere contralateral to the source of pain or in the dominant hemisphere when the pain is not specific to one side.17 The location of M1 is determined by the C3/C4 coordinates according to the International 10–20 System for electroencephalography electrodes. Anode stimulation at M1 can potentially alleviate pain by activating neural circuits located in the precentral gyrus, which consist of afferent and efferent connections interconnecting structures related to the sensory and emotional aspects of pain processing, such as the thalamus, anterior cingulate cortex and dorsolateral prefrontal cortex, or by facilitating the descending inhibitory control of pain.17 18
As a result, anodic stimulation on the primary motor cortex may reduce pain perception and provide temporary plastic changes in target areas.16 19–21 Although some studies suggested promising benefits of tDCS in chronic pain syndromes,20–23 a Cochrane review11 highlighted that evidence regarding tDCS in this population is still low due to the limitations of studies.
The hypothesised mechanism by which tDCS promotes plasticity is calcium dependent at glutamatergic synapses, possibly regulated by the reduction of the neurotransmitter GABA activity. This calcium-dependent plasticity is a process in which changes in calcium ion concentration play a fundamental role. Furthermore, it is important to emphasise that the magnitude and directionality of the plasticity induced by tDCS do not follow a linear relationship. This means that it is not simply a matter of stimulation intensity or duration; other factors, such as individual characteristics and the current state of the brain, also play a significant role in how tDCS influences synaptic plasticity.24
tDCS may be optimised when combined with other techniques, obtaining synergistic and additive effects.25 Some studies showed the association of tDCS with transcutaneous electrical nerve stimulation,25–27 cognitive–behavioural therapy11 28 and different therapeutic exercise modalities15 21 29 for chronic pain management. A review by Cardenas-Rojas et al15 showed moderate to strong effects favouring physical exercises combined with non-invasive cranial stimulation over placebo or isolated exercises, suggesting the association of these techniques as a viable alternative for chronic pain management.
The literature also demonstrated that exercise was more effective than other treatments for chronic low back pain and should be incorporated into patient management.30–32 Physical activity also increased the release of beta-endorphins related to motivation and pleasure, modulated intracortical excitability and has been associated with increased endogenous opioids in healthy individuals and individuals with pain, regulating nociception.33–36 Furthermore, Pilates-based exercises are recommended for healthy individuals or individuals under rehabilitation37 38 due to the benefits in physical and psychological function, such as balance, flexibility, muscle strength, endurance, pain, incapacity, mental health and quality of life.37–39 In this sense, tDCS combined with exercises may help restore the endogenous pain modulation system, decreasing pain perception,15 enabling better performance during exercise and increasing motor performance.40
To our knowledge, only one study assessed the effects of tDCS combined with strengthening exercises in individuals with chronic low back pain.29 However, this was a pilot study conducted with a small sample size, in which tDCS was performed before the physical activity and not simultaneously, as our study proposes.29 Therefore, we aimed to assess the effects of tDCS combined with Pilates-based exercises compared with sham stimulation combined with Pilates-based exercises on pain, disability, central sensitisation, quality of life and medication use in individuals with non-specific chronic low back pain. We hypothesised that both techniques performed simultaneously will reduce pain and improve exercise performance.
Methods and analysis
Study design
This will be a prospective, two-arm, double-blind randomised controlled trial (figure 1) with participants, outcome assessor and statistician blinded. Plan for data collection is from November 2023 to July 2024.
Flow diagram of the planned protocol. tDCS, transcranial direct current stimulation.
In addition, this trial protocol was written according to Standard Protocol Items: Recommendations for Interventional Trials 2013 checklist41 (online supplemental material A), and the study design schedule is presented below (figure 2).
Supplemental material
Study design schedule in accordance with the Standard Protocol Items: Recommendations for Interventional Trials checklist. tDCS, transcranial direct current stimulation.
Participants
The sample size was based on a relation of superiority for a parallel group trial with normal data, calculated on the website https://app.sampsize.org.uk/. Thirty individuals are necessary considering that pain intensity measured with a Numerical Pain Rating Scale (NPRS) as the primary outcome. A minimum clinically important difference of 3 points is expected for this measurement,42 and a population SD of 2.4.43 The design will involve two groups, a statistical power of 90% and an alpha value of 5%. A dropout rate of 20% is expected, so the final sample size required will be 36 individuals, 18 per group.
Voluntary individuals will be invited after disclosing verbal and printed material in the community; orthopaedic, rheumatological and Pilates clinics; primary healthcare in the region; and social media. We will randomly allocate the individuals into groups performing active tDCS+exercise (EG) or sham tDCS+exercise (SG), and outcome measures will be assessed at the time points shown in table 1.
Time point of outcomes
Recruited individuals will be men and women between 18 and 65 years with history of non-specific low back pain for more than 12 weeks44 and minimum pain intensity of 3 points on the NPRS.44 We will exclude those with diagnosis of fracture, diseases or spinal surgery in the last year; fibromyalgia; low cognitive level, assessed by the Mini-Mental State Examination (applied when necessary); presence of central neurological (eg, Parkinson’s disease and stroke) or psychiatric (eg, depression and schizophrenia) diseases; history of epileptic illness or seizure; brain implants; pacemaker; or pregnancy. Individuals will be able to continue medications during the study, but type and dosage will be recorded. Those included will be informed about the study procedures, including the side effects of the intervention and sign the informed consent form (online supplemental material B).
Supplemental material
Randomisation
An independent researcher, who is not involved in the allocation process, will individually randomise the individuals into EG and SG groups using block design through the randomization.com website; the same researcher will be responsible for placing the randomised order of individuals into opaque and sealed envelopes. Three researchers will conduct the study: researcher one (R1), responsible for assessments; researcher two (R2), responsible for the intervention protocol; and researcher three, responsible for the statistical analysis.
Assessments
We will conduct a pilot study to assess the adequacy of all study procedures and train the researchers involved. Its primary objective is to assess the viability, practicality and effectiveness of the methods, protocols and procedures that will be employed in the full study. It serves as a ‘trial before the trial’, enabling the identification of potential issues and fine-tuning of project details. First, in assessments, the included individuals will fill out an evaluation form containing personal and anthropometric data and questions about medication use. Assessments will be blindly conducted by R1 at baseline (T0), after 4 weeks of intervention (T1) and after 1 month of follow-up from T1 (T2). The data will be collected and stored in electronic capture.
Primary outcomes
Physical and emotional function, pain, satisfaction with treatment, adverse events and disposition are important measures to assess in individuals with chronic pain.45 Therefore, we will use the NPRS and the Roland-Morris Disability Questionnaire at T1 to assess pain and disability, respectively, as primary outcome measures.
Pain
Low back pain intensity will be measured using a Numerical Pain Scale consisting of 11 items, in which 0 is no pain and 10 is the worst possible pain. Individuals will be instructed to mark the number that best reflects pain intensity in the last 24 hours and while performing flexion–extension of the lumbar spine during assessments.46
Disability
The Roland-Morris Disability Questionnaire translated and adapted for the Brazilian population47 48 will assess functional performance associated with low back pain. It consists of a 24-item scale describing everyday situations that individuals have difficulty performing due to low back pain; 0 represents no disability and 24 represents severe disability.49
Secondary outcomes
Central sensitisation
Central sensitisation will be measured using the Central Sensitization Inventory, a valid and reliable instrument to screen individuals for assessment and clinical outcomes.50 51 The first part of this self-report instrument (scoring from 0 to 100) measures 25 somatic and emotional symptoms, while the second part relates to specific previous diagnoses. The severity level is classified as subclinical, mild, moderate, severe or extreme.52
Quality of life
The 36-Item Short Form Health Survey translated and validated to Portuguese will assess the quality of life. This multidimensional questionnaire comprises 36 items divided into eight subscales: (1) limitations in physical activities because of health problems; (2) limitations in social activities because of physical or emotional problems; (3) limitations in usual role activities because of physical health problems; (4) bodily pain; (5) general mental health (psychological distress and well-being); (6) limitations in usual role activities because of emotional problems; (7) vitality (energy and fatigue); and (8) general health perceptions.53 54
Pressure pain threshold
Pain threshold will be measured using a pressure algometer with a tip of 1 cm2. A perpendicular and progressive force will be applied to the skin at a rate of 1 kgf/s until the individual reports that the pressure sensation has changed to pain (threshold).55 Measurements will be performed 5 cm lateral to the spinous processes of L3 and L5 on the most affected side, according to reports of the individual.56 If the individual does not differentiate the most painful side, the measurement will be performed on the dominant side. Three measurements will be obtained at each point (30 s between measurements), and we will use the average of the two closest attempts for analysis.57 Also, a pre-familiarisation test will be previously performed on the forearm of the dominant limb.
Global impression of change
The Patient Global Impression of Change Scale will access the global impression of change after each session and during T1 and T2 assessments. This scale has 7 points, in which 1 represents no change or worse and 7 represents very much improved.58
Adverse events
Individuals will be asked about adverse or unexpected side effects experienced after each session and at T1 and T2 assessments.
Medication use
Medication use will be monitored in all assessments and intervention sessions. Individuals will be asked about the medication and dose.
Intervention
Intervention protocols will be performed three times a week, in an interleaved way, for 4 weeks, totalling 12 sessions. The sessions will be individual, face-to-face, offered by a trained physiotherapist and carried out at the Outpatient Rehabilitation Service of the Federal University of Rio Grande do Norte, Brazil. Before starting, the level of physical activity will be recorded and individuals will be instructed to not initiate any type of exercise or treatment for their condition.
The EG group will receive stimulation using a direct current stimulator (Genius, NKL, Brazil), in which a pair of porous electrodes soaked in saline solution (10–15 mL per electrode) will be fixed to the head with non-conductive elastic bands. The centre of the active electrode (anode) will be positioned in the primary motor cortex (M1), corresponding to the area C3 and C4, according to the mapping 10–20 of the electroencephalography, contralateral to the predominant side of pain.59 If pain is bilateral or central, the electrode will be positioned contralateral to the dominant side.60 The reference electrode (cathode) will be positioned horizontally in the contralateral supraorbital region (Fp2 area). The applied current intensity will be 2 mA11 15 26 29 with rise and fall ramps of 30 s at the beginning and end of the session, respectively26 55 (30 min of total treatment time).26 61
It is important to highlight that tDCS generally provides mild and transient adverse effects in nature, primarily manifesting as sensations of tingling, itching, burning, and, in some cases, may involve skin lesions or contact dermatitis and headaches.62 There are no records of noticeable adverse effects or significant cognitive effects in healthy individuals undergoing tDCS.63 It is worth noting that adverse effects appear to be correlated with variables such as skin conditions, allergic predisposition, high current intensities, stimulation duration, multiple sessions, use of small-sized electrodes, electrode configuration, uneven skin pressure, sponge salinity and sponge degradation during the procedure.63
The EG group will also be submitted to an exercise programme (online supplemental appendix A) of 30 min combined with tDCS. The Pilates-based exercise programme will consist of stretching, spinal mobilisation, stabilisation and strengthening of core muscles that will be progressed weekly depending on the evolution of each individual.64–68 The assessment of individual exercise progression will be conducted on a weekly basis, based on the quality of movement. In the event of the patient being unable to perform a specific exercise in a satisfactory standard, they will be asked to perform the equivalent exercise of the previous week while keeping the other exercises unchanged. The SG group will perform the same procedures as the EG, but the stimulator will be turned off after 30 s; individuals will not receive the current for the rest of the session.
Supplemental material
Interventions may be interrupted or modified in the following circumstances: failure to carry out the treatment or to return for the assessments, insufficient adherence to protocol or incomplete data. As strategies to improve intervention adherence, individuals will be notified by messages and calls reminding them of interventions and assessments. On the last day, information about their progress and continuity of treatment at home will be provided, and every effort will be made to ensure that the individuals who discontinued the treatment return to the follow-up.
Blinding
To ensure blinding, envelopes will be opened by R2 only at the time of the first session, while the baseline assessment will be conducted before opening envelopes to avoid the influence of group sequencing; only R2 will know the intervention protocol. After data collection, groups will be colour coded (blue and green) by R2 to enable a blind statistical analysis. The corresponding colours of each group will only be revealed after data analysis. Unblinding will not be permissible in any circumstance during the trial.
Moreover, individuals will be blinded to tDCS and instructed to avoid talking about the experience with other individuals involved in the study. In addition, study interventions and measurements will occur at separate places, while treatment sessions will be individualised to facilitate the blinding. After the follow-up, we will ask which group (active tDCS, tDCS sham or I do not know) individuals believed to be participating.
Statistical analysis
Data will be analysed using the SPSS V.20.0 and GraphPad Prism V.5 (GraphPad Prism Software, La Jolla, California, USA). Baseline results will be compared between groups using one-way analysis of variance (ANOVA) to verify data homogeneity. Levene’s test will verify the homogeneity of variances, and Mauchly’s test of sphericity will validate the correlation of repeated measures. The Greenhouse-Geisser correction (ε) will be applied if sphericity is violated.
A two-way mixed model ANOVA (2×3) will be used to analyse differences between groups (EG×SG), the effect of the time variable (T0, T1 and T2) and time×group interaction. The one-way ANOVA test with Tukey’s post hoc for multiple comparisons will determine the mean differences between groups when time×group interaction is detected. Mean differences and 95% CIs will be calculated to indicate the accuracy of estimates. Missing data will be included using analysis by data imputation through mixed linear models.69 The η2 will be calculated as a measure of effect size, and values will be considered small (η2=0.01), moderate (η2=0.06) or large (η²=0.14). Statistical significance will be set at ≤0.05.
Patient and public involvement
No patients were involved in this study as it is a protocol design. However, in the development of the clinical trial, patients will be required.
Trial status
At the time of study submission, the team was already trained to apply the techniques and was initiating the literature review.
Clinical relevance
tDCS is a useful tool for chronic pain. Its use combined with other techniques may optimise their effects and add synergistic and additive responses, contributing to pain reduction and improvement of quality of life.
This topic is still scarce in the literature, since tDCS is a recent method for treating chronic pain. Studies about tDCS and low back pain are limited and its effects in association with other techniques are poorly studied.
The results of this study will indicate whether tDCS combined with Pilates-based exercises is effective for treating non-specific chronic low back pain, decreasing pain, improving functionality and quality of life, and increasing adherence and satisfaction with the treatment.
Ethics and dissemination
Our study will be developed at the outpatient rehabilitation service of the Physiotherapy Department of the Federal University of Rio Grande do Norte and will be conducted according to Resolution 466/12 of the National Health Council and the Declaration of Helsinki. The study was approved by the Ethics and Research Committee of the Faculty of Health Sciences of Trairí (report number: 5.411.244) and registered on ClinicalTrials.gov (NCT05467566). Any protocol modifications after ethics approval will be communicated to the Ethics Committee.
In addition, all participants involved will be invited to provide their written informed consent prior to participating. The informed consent form will comprehensively address the study’s purposes, the procedures involved, potential risks and benefits, as well as data confidentiality. These data will be securely stored in a purpose-built database by the responsible researcher for a period of 5 years and only the main investigators will have access to the final trial dataset. It will be emphasised that participation is voluntary and that participants can withdraw their consent at any time without facing penalties.
The dissemination of the results of this study will be disclosed ethically in academic settings, conferences and/or scientific publications, as well as on social media platforms such as university websites and other social networks, with the aim of expanding the reach of knowledge to clinicians, patients and other interested parties.
Ethics statements
Patient consent for publication
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Funding This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (CAPES) (Finance Code 001).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.