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Chronic pathology;

Affects about 1% to 3% of the population;

Hard to manage and understand;

Prevalence increases with age, being more frequent in women and between 30 and 35 years;

Symptoms: widespread pain (the most common), cognitive impairment ("fibro-fog” and memory loss), sleep changes, physical and mental exhaustion, blurred vision, among others.

Has no specific signals or exams that can lead to a diagnostic, although there is some criteria sets.

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Changes in cortical-subcortical processing;

Reduced intrinsic conectivity between important areas of the brain linked to pain and the primary sensorimotor sites;

Increased activity in pain areas of the brain;

Less grey matter in cortical and subcortical sites;

Excitatory neurotransmitters, which leads to hypersensitivity (linked to issues in the amplification of pain or in the central nervous system).

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Pain generated by mental status when the copying systems fail (makes a difference in the intensity of the pain felt);

Psychological disorders (e.g. depression).

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Hypersensitivity to surrounding stimulus (e.g. light, sounds, odors and pain).

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Pain felt in FM;

Pain that continues to exist even after the stimulus that causes her its gone;

Induced by damages in the nervous system that are almost entirely reversible and lead to hypersensitivity.

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Major sensitivity to pressure at some precise locations, which is not enough to define the condition, but helps excluding others.

It is also possible to give a questionnaire to evaluate the ones who have more risk of developing the disease.

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Functional magnetic resonance imaging (fMRI)

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Functional magnetic resonance imaging (fMRI)

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Gives the degree of connection between the different brain sites, the neuronal activation of brain areas linked to pain and studies physiologic factors associated with pain.

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This condition can develop due to genetic causes, life experiences, cognitive and emotional status, and the ability to deal with stress.

Has no stipulated effective treatments, since it is difficult to define agreed criteria for its classification and diagnostic.

Some approaches: physical exercise, drugs, education about the condition and psychotherapy.

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Neurostimulation: transcranial magnetic stimulation (TMS) and transcranial electric stimulation (TES).

Both strategies are considered safe and noninvasive with the aim of adjust the activity of the cortex.

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Although both are effective, studies indicate that TMS has better results in controlling the symptoms.

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Help control the pain;

Stimulation given to the brain by electric stimuli;

Applied through single-pulse TMS (to analyze the brain function), repetitive TMS (modulation of the activity of cortical areas) or theta burst stimulation (provides changes in the excitability of the motor sites of the cortex).

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Leads to motor-evoked potential (MEP).

Uses a coil placed in the scalp to produce magnetic fields, which leads to electrical currents.

Intensity can be affected by: scalp, meninges, bones, direction and shape of the coil, number and pattern of pulses, among others.

Electric fields are stronger in superficial regions of the cortex than in subcortical sites.

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M1 and dorsolateral prefrontal cortex (DLPFC) are two sites of the brain that are connected with the operation and control of the feeling of pain.

Ideal for TMS modulation since it is easily accessible and is responsible for the accomplishment of the movements.

Some studies indicate that M1 can be affected by muscle pain, being related to chronic musculoskeletal disorders.

In FM patients, it is possible to have a M1 neuronal metabolic dysfunction.

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Circular coil: stimulation of surface motor areas of the brain and leads to a more spread stimulus;

Figure-of-eight coil: focused current;

H-coil: stimulation of deep layers of the brain;

Double-cone coil: stimulation of deep layers (up to 6 cm) of the cortex.

Among others.

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To evaluate the excitability of the motor sites of the brain and to provide information about the sensorimotor system, which is essential to the prognostic and diagnostic of the disease.

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For long periods of time can improve the quality of life of FM patients since it helps to reduce pain.

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Ansari, A. H., Pal, A., Ramamurthy, A., Kabat, M., Jain, S., & Kumar, S. (2021). Fibromyalgia Pain and Depression: An Update on the Role of Repetitive Transcranial Magnetic Stimulation. ACS Chemical Neuroscience, 12(2), 256–270. https://doi.org/10.1021/acschemneuro.0c00785

Argaman, Y., Granovsky, Y., Sprecher, E., Sinai, A., Yarnitsky, D., & Weissman-Fogel, I. (2022). Clinical Effects of Repetitive Transcranial Magnetic Stimulation of the Motor Cortex Are Associated With Changes in Resting-State Functional Connectivity in Patients With Fibromyalgia Syndrome. Journal of Pain, 23(4), 595–615. https://doi.org/10.1016/j.jpain.2021.11.001

Brighina, F., Curatolo, M., Cosentino, G., De Tommaso, M., Battaglia, G., Sarzi-Puttini, P. C., Guggino, G., & Fierro, B. (2019). Brain modulation by electric currents in fibromyalgia: A structured review on non-invasive approach with transcranial electrical stimulation. Frontiers in Human Neuroscience, 13(February), 1–14. https://doi.org/10.3389/fnhum.2019.00040

Chang, W. J., O’Connell, N. E., Beckenkamp, P. R., Alhassani, G., Liston, M. B., & Schabrun, S. M. (2018). Altered Primary Motor Cortex Structure, Organization, and Function in Chronic Pain: A Systematic Review and Meta-Analysis. Journal of Pain, 19(4), 341–359. https://doi.org/10.1016/j.jpain.2017.10.007

Che, X., Cash, R. F. H., Luo, X., Luo, H., Lu, X., Xu, F., Zang, Y. F., Fitzgerald, P. B., & Fitzgibbon, B. M. (2021). High-frequency rTMS over the dorsolateral prefrontal cortex on chronic and provoked pain: A systematic review and meta-analysis. Brain Stimulation, 14(5), 1135–1146. https://doi.org/10.1016/j.brs.2021.07.004

Choo, Y. J., Kwak, S. G., & Chang, M. C. (2022). Effectiveness of Repetitive Transcranial Magnetic Stimulation on Managing Fibromyalgia: A Systematic Meta-Analysis. Pain Medicine (United States), 23(7), 1272–1282. https://doi.org/10.1093/pm/pnab354

Forogh, B., Haqiqatshenas, H., Ahadi, T., Ebadi, S., Alishahi, V., & Sajadi, S. (2021). Repetitive transcranial magnetic stimulation (rTMS) versus transcranial direct current stimulation (tDCS) in the management of patients with fibromyalgia: A randomized controlled trial. Neurophysiologie Clinique, 51(4), 339–347. https://doi.org/10.1016/j.neucli.2021.03.002

Kankane, A. K., Pandey, A. K., Ramesh, P. M., & Agarwal, A. (2024). Role of Repetitive Transcranial Magnetic Stimulation in Treatment of Fibromyalgia: A Randomized Controlled Trial. 2024 Annals of Indian Academy of Neurology. https://doi.org/10.4103/aian.aian_1041_23

Kim, H., Jung, J., Park, S., Joo, Y., Lee, S., & Lee, S. (2022). Effects of Repetitive Transcranial Magnetic Stimulation on the Primary Motor Cortex of Individuals with Fibromyalgia: A Systematic Review and Meta-Analysis. Brain Sciences, 12(5). https://doi.org/10.3390/brainsci12050570

Klomjaia, W., Katzb, R., & Lackmy-Vallée, A. (2015). Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS). Annals of Physical and Rehabilitation Medicine, 58(4), 208–213. https://doi.org/10.1016/j.rehab.2015.05.005

Narayana, S., Zang, W., Rogers, W., Strickland, C., Franklin, C., Lancaster, J. L., & Fox, P. T. (2009). Concurrent TMS to the primary motor cortex augments slow motor learning. Neuron, 61(1), 1–7. https://doi.org/10.1016/j.neuroimage.2013.07.024.Concurrent

Pacheco-Barrios, K., Lima, D., Pimenta, D., Slawka, E., Navarro-Flores, A., Parente, J., Rebello-Sanchez, I., Cardenas-Rojas, A., Gonzalez-Mego, P., Castelo-Branco, L., & Fregni, F. (2022). Motor cortex inhibition as a fibromyalgia biomarker. Brain Network and Modulation, 1(2), 88–101. https://doi.org/10.4103/2773-2398.348254

Sarzi-Puttini, P., Giorgi, V., Marotto, D., & Atzeni, F. (2020). Fibromyalgia: an update on clinical characteristics, aetiopathogenesis and treatment. Nature Reviews Rheumatology, 16(11), 645–660. https://doi.org/10.1038/s41584-020-00506-w

Shahat, R. M. E., Sebaie, M. A. E., Ahmed, S. F., Fawaz, S. I., Kamel, M. A., & Nassef, M. A. (2025). Repetitive transcranial magnetic stimulation as a modality of treatment in patients with fibromyalgia. Egyptian Rheumatology and Rehabilitation, 52(1). https://doi.org/10.1186/s43166-025-00302-y

Short, E. B., Borckardt, J. J., Anderson, B. S., Frohman, H., Beam, W., Reeves, S. T., & George, M. S. (2011). Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: A randomized, controlled pilot study. Pain, 152(11), 2477–2484. https://doi.org/10.1016/j.pain.2011.05.033

Silva, V. A., Baptista, A. F., Fonseca, A. S., Carneiro, A. M., Brunoni, A. R., Carrilho, P. E. M., Lins, C. C., Kubota, G. T., Fernandes, A. M. B. L., Lapa, J. D. S., dos Santos, L. M., Sasso, I., Monte-Silva, K., Poindessous-Jazat, F., Mori, N., Miki, K., Baltar, A., Tanaka, C., Teixeira, M. J., … Ciampi de Andrade, D. (2025). Motor cortex repetitive transcranial magnetic stimulation in fibromyalgia: a multicentre randomised controlled trial. British Journal of Anaesthesia, 134(March), 1756–1764. https://doi.org/10.1016/j.bja.2024.12.045

Siracusa, R., Di Paola, R., Cuzzocrea, S., & Impellizzeri, D. (2021). Fibromyalgia: Pathogenesis, mechanisms, diagnosis and treatment options update. In International Journal of Molecular Sciences (Vol. 22, Issue 8). https://doi.org/10.3390/ijms22083891

Tanwar, S., Mattoo, B., Kumar, U., & Bhatia, R. (2020). Repetitive transcranial magnetic stimulation of the prefrontal cortex for fibromyalgia syndrome: A randomised controlled trial with 6-months follow up. Advances in Rheumatology, 60(1). https://doi.org/10.1186/s42358-020-00135-7

Zhang, J. H., Liang, J., & Yang, Z. W. (2023). Non-invasive brain stimulation for fibromyalgia: current trends and future perspectives. Frontiers in Neuroscience, 17(October), 1–8. https://doi.org/10.3389/fnins.2023.1288765

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High-frequency repetitive transcranial magnetic stimulation (rTMS) has been investigated as a therapeutic approach for fibromyalgia, efficacious as an add-on therapy for people who remain symptomatic despite optimised best medical therapy. especially when applied to the dorsolateral prefrontal cortex (DLPFLC) and the primary motor cortex (M1).

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Pain: High-frequency rTMS (≥10 Hz) applied to the left DLPCB can reduce the intensity of subjective pain (short-term), improve symptoms, such as fatigue and cognitive dysfunction, influence connectivity with the limbic system (amygdala, cingulate), responsible for the emotional component of pain.

Quality of Life: Effective in improving pain and associated symptoms (depression and anxiety) along with QoL. Improving of physical functioning in fibromyalgia, and it may also improve aspects of pain beyond pain intensity, such as stifness.

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Pain: High-frequency stimulation (10–20 Hz) on M1 appears to activate descending inhibitory circuits that reduce pain perception. It can also modulate pain-related subcortical areas, such as the thalamic nucleus and periaqueductal gray matter. Low-frequency also reduces pain perception.

Quality of Life: Significant improvement in the quality of life of the patients although it manifests late (detected during the follow-ups after the stimulation sessions).

Functional Connectivity: Active rTMS led to improvements in fibromyalgia symptoms, associated with changes in functional connectivity in brain areas related to pain processing and modulation.

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In fibromyalgia, there is central hypersensitization, an abnormal amplification of pain at the level of the central nervous system.

rTMS acts by inducing magnetic currents in the cortical tissue, capable of modulating neuronal excitability

High frequency (~10 Hz) → LTP-like effects: increases cortical excitability, antinociceptive effects by activating descending pain inhibitory controls.

Low frequency (~1 Hz) → LTD-like effects: inhibitory effect on brain, significantly reduce pain and related symptoms by targeting spinal pain circuits and top–down modulation

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Brain Network Dysregulation in Fibromyalgia

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Brain Network Dysregulation in Fibromyalgia

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Functional neuroimaging studies (fMRI and PET) indicate changes in the following regions in patients with fibromyalgia

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rTMS is associated with changes in several neurotransmitters, including:

NMDA: Disrupted neurotransmitter concentrations, notably glutamate NMDA receptor, contribute to central sensitization and fibromyalgia pain development. rTMS potentially mitigates pain by top-down neurotransmitter modulation

Glutamate/GABA: reinstates GABAergic and glutamatergic system balance, curbing excitatory and bolstering inhibitory neurotransmitter activity for fibromyalgia pain relief.

rTMS regulates dopamine, serotonin, and opioid peptide receptors, restoring homeostasis

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What method should be applied to treat chronic pain in FM using TMS?

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What method should be applied to treat chronic pain in FM using TMS?

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Pacheco-Barrios et al., 2022; Sarzi-Puttini et al., 2020; Short et al., 2011; Siracusa et al., 2021

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Pacheco-Barrios et al., 2022; Sarzi-Puttini et al., 2020; Siracusa et al., 2021

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Sarzi-Puttini et al., 2020

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Sarzi-Puttini et al., 2020

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Siracusa et al., 2021

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Sarzi-Puttini et al., 2020; Siracusa et al., 2021

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Brighina et al., 2019

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Forogh et al., 2021

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Pacheco-Barrios et al., 2022

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Ansari et al., 2021

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Short et al., 2011; Klomjaia et al., 2015

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Klomjaia et al., 2015

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Short et al., 2011; Klomjaia et al., 2015

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Kim et al., 2022; Silva et al., 2025

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Argaman et al., 2022; Che et al., 2021; Choo et al., 2022; Kankane et al., 2024; Kim et al., 2022; Silva et al., 2025

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Zhang et al., 2023

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Argaman et al., 2022; Brighina et al., 2011; Chang et al., 2018; Narayana et al., 2009; Short et al., 2011; Tanwar et al., 2020

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Kankane et al., 2024; Shahat et al., 2025

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Silva et al., 2025