Fibromyalgia is a chronic widespread pain condition affecting up to 5% of the population. It is characterized by chronic musculoskeletal pain, fatigue, sleep disturbances and tenderness. The exact causes are unknown but theories suggest it may be due to abnormalities in pain processing by the central nervous system.
Current treatments such as medications, exercise and therapy are not curative so there is a need for more effective therapies targeting the central nervous system.
Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation where a weak electrical current is passed between electrodes on the scalp to modulate the activity of underlying brain regions. It has been suggested tDCS could help treat fibromyalgia by altering abnormal pain processing in the brain. This systematic review and meta-analysis aimed to evaluate the current evidence on the effectiveness of tDCS for reducing fibromyalgia pain.
Methods:
The authors searched major medical databases for randomized controlled trials and crossover studies investigating tDCS for fibromyalgia pain relief in adults compared to a sham stimulation control group. Risk of bias was assessed and meta-analysis conducted on pain intensity data, reported on a 0-10 scale.
Results:
14 studies with 452 mainly female participants were reviewed. 10 were randomized controlled trials and 4 were crossover studies. tDCS was applied to the left motor cortex in most studies, using 2mA current for 20 minutes per session, over 5-10 sessions.
Meta-analysis of 9 studies found active tDCS resulted in a small-moderate reduction in pain intensity ratings versus sham. This amounted to a percentage change of 17%, considered clinically meaningful. However, there was substantial heterogeneity across studies. Excluding one outlier study reduced heterogeneity but also reduced the pain relief effect to only 12% – below the threshold for clinical importance.
Most studies had low risk of bias apart from lack of sample size calculations. Mild adverse effects like scalp tingling were reported.
What are the optimal stimulation parameters (electrode placement, current intensity, duration) to achieve maximum pain relief in fibromyalgia patients?
Most studies placed the anode over the left motor cortex (M1) and cathode over the right supraorbital region, using a current intensity of 2mA for 20 minutes per session. However, there is likely substantial variability in current flow and brain regions modulated between individuals using this electrode montage. Computational modeling indicates the cortical regions stimulated depend on many factors including electrode size, position, and individual anatomy. More research is needed to model current flow patterns and determine optimal individualized electrode placements. Lower stimulation intensities of 1-1.5mA may be equally effective and warrant testing. Shorter or longer stimulation durations, or more sessions, could yield greater effects. Optimizing parameters would allow more focused stimulation of relevant cortical targets.
Can tDCS be combined or sequenced with other therapies like medications, exercise, or psychological interventions to boost treatment effects?
Only one study combined tDCS with exercise and found enhanced pain relief versus either intervention alone. tDCS could be combined with antidepressants or anti-epileptics to augment pain relief through synergistic effects on overlapping neural pathways.
Sequential or concurrent therapy with psychological techniques like CBT could promote helpful cognitive and behavioral changes alongside tDCS-induced neuroplasticity. Physical therapies and exercise could also complement tDCS through top-down and bottom-up mechanisms. Testing tDCS as an add-on treatment would determine if combinatorial approaches provide greater clinical improvements in fibromyalgia.
Are there individual differences that predict response to tDCS treatment?
Factors like age, gender, genetics, fibromyalgia duration, psychosocial variables, and baseline brain physiology could all influence tDCS effects. Younger patients, or those with shorter illness duration or fewer secondary psychiatric symptoms, may respond better. Neuroimaging and EEG measures of brain structure, function and neurochemistry could potentially be used to select optimal responders.
Testing interactions between these factors and tDCS response is important to establish whether treatment should be personalized based on individual differences.
Does repeated or maintenance tDCS treatment confer any long-term pain relief in fibromyalgia?
Current evidence comes from short treatment courses of 5-10 sessions. Longer interventions and follow-up periods are needed to assess whether tDCS can induce sustained, cumulative pain relief. Repeated tDCS boosters could conceivably maintain treatment benefits. Only a subset of studies did 1-month follow-up with mixed results. Longer-term follow up of 3-6 months would determine if repeated tDCS can produce stable, long-lasting improvements in fibromyalgia pain. This would support its potential as a maintenance therapy.
Through what mechanisms does tDCS over motor cortex provide pain relief?
The motor cortex is thought to modulate pain through connections with the thalamus, basal ganglia and descending inhibitory pathways. tDCS may alter excitability of motor regions, affecting their communication with these areas to inhibit pain signaling. However, the mechanisms are unclear as tDCS over motor cortex does not always increase excitability.
MRI and PET studies suggest tDCS may reduce activation or connectivity within pain processing networks involving the insula, cingulate, and prefrontal cortex. tDCS could also alter neurochemistry like GABA and glutamate. Simultaneous tDCS-EEG-fMRI is needed to elucidate the pharmacological, metabolic and network effects underlying pain relief.
Which brain regions should be targeted for optimal fibromyalgia pain relief?
As fibromyalgia likely involves dysfunctional pain processing networks, targets beyond motor cortex should be considered. The dorsolateral prefrontal cortex regulates anticipatory pain responses so tDCS to modulate activity here could improve coping and pain inhibition. Stimulating the thalamus or anterior cingulate could disrupt abnormal connectivity within pain matrices. Insula stimulation could modify interoceptive processing and affective pain components.
Computational models combined with functional neuroimaging could identify patient-specific targets within pain processing circuits. Multi-electrode tDCS could then stimulate these optimally.
Can tDCS be optimized in a personalized, brain state-dependent way for each patient?
Brain state variability affects tDCS response, suggesting tailored protocols based on each individual’s brain activity could improve results. EEG-guided tDCS approaches deliver stimulation timed to particular oscillatory rhythms like alpha waves. Closed-loop systems incorporate EEG feedback to adjust stimulation parameters in real-time.
Machine learning using EEG and neuroimaging data could construct predictive models and classifiers to optimize protocols for each patient’s brain state and anatomy. Such personalized approaches may be more effective than standardized stimulation.
What patient-reported outcomes beyond pain intensity does tDCS improve in fibromyalgia?
Few studies assessed effects on outcomes like fatigue, sleep, cognitive function, mood and quality of life, which are impacted in fibromyalgia.
Multidimensional assessments are needed to fully evaluate tDCS effects. Pain involves sensory, affective and cognitive processes so tDCS could improve emotional or functional status through central mechanisms beyond sensory pain relief. However, large variability in methodology and outcome measures limits conclusions about broader efficacy. Standardized batteries assessing multiple patient-reported domains should be implemented in future clinical trials.
Is tDCS cost-effective for managing fibromyalgia pain compared to current standard treatments?
No health economic evaluations have been conducted yet. tDCS devices have relatively low start-up costs compared to other neuromodulation techniques like repetitive TMS. But the costs of recurrent clinic visits for supervised, repeated sessions could become substantial.
Cost-effectiveness analyses should compare tDCS‐associated healthcare costs and impacts on quality of life/disability against current pharmacological, physical and psychological therapies for fibromyalgia. These would determine if tDCS provides good value for money. Models should also evaluate costs if tDCS was implemented for at-home self-administration without clinic visits.
How does tDCS compare or combine with other neurostimulation techniques like repetitive TMS for fibromyalgia treatment?
A direct head-to-head comparison between tDCS and rTMS has not yet been conducted in fibromyalgia patients. Indirect comparisons suggest effect sizes are similar for pain relief. rTMS may have more robust evidence at present, but advantages of tDCS include lower cost, portability and easier sham control.
The techniques could have synergistic effects as rTMS modulates cortical excitability while tDCS is proposed to affect synaptic plasticity. Combining the modalities may produce greater or more sustained pain relief and anti-hyperalgesic effects. Further research directly comparing stimulation techniques and investigating combined protocols is warranted to determine optimal usage of non-invasive brain stimulation for fibromyalgia.
Conclusions:
This meta-analysis provides tentative evidence that tDCS may relieve fibromyalgia pain compared to sham stimulation. However, significant variability between studies and methodological weaknesses prevent definitive conclusions on its effectiveness being made at this stage.
There is a need for further research to optimize tDCS protocols and identify the underlying biological mechanisms of action. Larger, more rigorous clinical trials investigating effects on pain and other outcomes are needed before tDCS can be recommended for fibromyalgia treatment. Understanding the brain networks involved through neuroimaging and electroencephalography studies could help target tDCS more effectively in the future.
References
Lloyd DM, Wittkopf PG, Arendsen LJ, Jones AK. Is transcranial direct current stimulation (tDCS) effective for the treatment of pain in fibromyalgia? A systematic review and meta-analysis. The journal of pain. 2020 Nov 1;21(11-12):1085-100.
MD, PhD. Physical Medicine & Rehabilitation Physician from São Paulo - Brazil. Pain Fellowship in University of São Paulo.