TMS Pain Relief Approaches and Related Mechanisms

The International Association for the Study of Pain has designated the third Monday of October each year as "World Pain Day." Neuropathic pain (NP) refers to pain caused by damage or disease affecting the somatosensory system. It is characterized by injury to the central or peripheral nervous system and is one of the most difficult types of pain to treat in clinical settings, with an annual incidence rate of 0.82%.

Functional magnetic resonance imaging (fMRI) has enabled researchers to discover the potential pain-relieving effects of TMS. TMS can alleviate pain through multiple mechanisms, including altering cortical excitability, improving cerebral blood flow, activating or inhibiting pain perception areas, changing neural plasticity, influencing the hypothalamic-pituitary-adrenal (HPA) axis, and regulating neurotransmitters and inflammatory factors.

In areas such as chronic pain and neuropathic pain, TMS technology has already demonstrated significant therapeutic effects. In the 2019 "Evidence-Based Guidelines for TMS Therapy" published by the International Federation of Clinical Neurophysiology (IFCN), high-frequency rTMS stimulation of the contralateral M1 region is rated as an A-level recommendation for treating neuropathic pain. This shows that TMS can be confidently used in clinical practice to improve patients' pain symptoms.

We have reviewed the literature to gather treatment protocols for various pain-related indications using TMS and have provided a summary of the underlying mechanisms.

Migraine

• Protocol:

Target	Intensity	Frequency	Number of Trains	ITI	Number of Sessions
Occipital Cortex	100%RMT	iTBS(50Hz/5Hz)	20	10s	5 sessions per week for two weeks

• Possible Mechanisms: TBS may affect the formation and spread of cortical spreading depression (CSD), which is part of the neurological theory of migraines, thereby reducing migraine attacks. It may also influence the process of activating the trigeminal nerve endings around cerebral blood vessels, as proposed in the trigeminovascular reflex theory of migraines, affecting the pain transmission pathways in patients.

Postherpetic Neuralgia

• Protocol

Target	Intensity	Frequency	Train Duration	ITI	Total Pulses
Healthy Side M1	80%RMT	10Hz	0.5S	3s	1500

• Possible Mechanism: Stimulating the M1 region may excite the thalamus through the cortico-thalamic circuit, thereby inhibiting the transmission of pain signals through the spinothalamic pathway.

Neuropathic Pain Following Spinal Cord Injury

• Protocol

Target	Intensity	Frequency	Train Duration	ITI	Total Pulses
M1 on the Painful side of the body	110%RMT	10Hz	5s	25s	1500

• Possible Mechanism: The analgesic effect of TMS stimulation on the motor cortex depends on altering the activity of the motor cortex and inducing plasticity changes, as well as its projections to brain areas involved in pain processing, such as the thalamic nuclei, anterior cingulate cortex, and periaqueductal gray in the brainstem.

Chronic Pain After Ischemic Stroke

• Protocol

Target	Frequency	Total Pulses	Duration
Bilateral M1	1Hz	1000	15min per side, 1 session per day

• Possible Mechanism: After localized current generation, stimulation induces the release of endogenous opioid peptides in the central nervous system while repairing damaged neuronal cells, thereby achieving a therapeutic effect on post-stroke pain.

Fibromyalgia

• Protocol

Target	Intensity	Frequency	Train Duration	ITI	Total Pulses
L-DLPFC	120%RMT	10Hz	4s	21s	3000

• Possible Mechanism: The DLPFC is a key area that regulates pain perception by directly modulating subcortical and cortical pathways. Additionally, the DLPFC is involved in multiple cognitive, emotional, and sensory networks, which can improve various symptoms of fibromyalgia, including mood and fatigue.

Primary Trigeminal Neuralgia

• Protocol

Target	Intensity	Frequency	Train Duration	ITI	Total Pulses
Healthy Side M1	80%RMT	10Hz	0.5s	3s	1500

• Possible Mechanism: rTMS acts on the cortical areas of the brain, influencing the trigeminal nerve by regulating neural conduction and neurotransmitter secretion, thereby improving facial movement.

Glossopharyngeal Neuralgia

• Stimulation Protocol: Use the iTBS mode, targeting the glossopharyngeal nerve.  
• Possible Mechanism: Peripheral magnetic stimulation generates analgesic effects by interfering with peripheral impulse conduction, activating large afferent nerve fibers, regulating peripheral nerves and dorsal root ganglia, affecting endogenous opioid pathways, and activating spinal and supraspinal inhibitory mechanisms.

Complex Regional Pain Syndrome (CRPS)

• Stimulation Protocol: Use the iTBS mode, targeting the superficial flexor muscles of the fingers.
• Possible Mechanism: Peripheral magnetic stimulation can increase proprioceptive signals flowing to the brain from the bottom up, thereby influencing neural plasticity as well as pain and motor control mechanisms.

Carpal Tunnel Syndrome

• Protocol

Target	Frequency	Train Duration	ITI	Total Pulses
median nerve	10Hz	1s	5s	1000

• Possible Mechanism: Stimulating the median nerve may project through pathways to the sensorimotor cortex, modulating cortico-spinal motor commands and increasing proprioceptive input, thereby enhancing cortical excitability and improving motor performance.

Lumbar Radiculopathy

• Protocol

Target	Frequency	Train Duration	ITI	Total Pulses
Lumbar	10Hz	0.5s	5s	1000

• Possible Mechanism: Peripheral repetitive magnetic stimulation significantly alleviates pain caused by lumbar radiculopathy, with notable improvements in electromyographic (EMG) indicators. The possible mechanisms include terminal nerve reinnervation or nerve sprouting.

Statement 

1. This content is organized by the Clinical Support Department of Shenzhen Yingchi Technology Co.,Ltd. Criticisms and corrections are welcome. For reprint, please indicate the source.

2. Reference:

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