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TMS Off-Label Treatment for Chronic Pain

Currently, treatment-resistant Depression, OCD, and migraine are the only conditions approved by the U.S. Food and Drug Administration (FDA) for TMS therapy.

However, clinical trials show that TMS can potentially benefit a wide range of other conditions not yet approved by the FDA.

Thus, despite the promising potential, TMS remains an investigational and off-label treatment for several conditions, one of which is chronic pain.

First-line treatments for chronic painful conditions are typically medications like anti-inflammatory medicines, muscle relaxants, antidepressants, anticonvulsants, and opioids. Other interventions include physical therapy or TENS.

However, not all people with chronic pain respond to them. Even people who respond are prone to severe adverse effects of these medications. To make things worse, these medicines negatively impact cognition, particularly executive functions, affecting the ability to work. Their addictive potential is also a concern. All these pitfalls can cause patients with chronic pain to stop the treatment.

Hence, experts have been hunting for other safe and effective therapeutic options for chronic pain, one of which is TMS.

How Does TMS Work for Chronic Pain?

Experts have been studying the application of TMS for various chronic painful conditions. rTMS presents a promising alternative, or at least an add-on, as it has been shown to alleviate pain without the risks of painkillers.

How rTMS helps alleviate chronic pain is largely unknown. However, a recent systematic review suggests that TMS tends to fine-tune the activities of neurons in an area called periaqueductal gray matter (PAG). This area of gray matter in the midbrain is best known to play a role in pain processing and reduction. Hence, stimulating the PAG via TMS in chronic pain may help induce analgesia (pain-relieving effects).

rTMS may also help with pain by tweaking the brain’s plasticity and activating inhibitory pain control systems.

In addition, activation of endogenous opioids may contribute to the pain-relieving effects of rTMS on the motor cortex.

The significant overlap between chronic pain and depression paves another way to effectively address painful symptoms, such as fibromyalgia. Because TMS alleviates depression, it can also help relieve the physical pain that often accompanies depression.

Besides, TMS helps modulate an area in the prefrontal part of the brain, which further moderates the pain sensation. As a result, pain scores drop.

Chronic painful conditions that seem to benefit from rTMS include:

Chronic Neuropathic Pain

Neuropathy (nerve damage) is a common complication of diabetes, affecting over 90% of patients with long-lasting disease. Pain is one of the main symptoms of diabetic neuropathy.

Research shows that rTMS applied over the motor cortex can relieve neuropathic pain, at least partially, if not entirely.

It is also seen that high-frequency (≥5 Hz) rTMS of the area of the brain that represents the legs opposite to the site of pain can help alleviate chronic nerve pain. A study published in The Egyptian Journal of Neurology, Psychiatry, and Neurosurgery showed considerable improvement in the symptoms of diabetic neuropathy after five days of high-frequency (10 Hz) rTMS sessions.

Trigeminal Neuralgia

Another chronic painful nerve disorder shown to benefit from TMS clinically is trigeminal neuralgia (TN). It is a condition in which sharp, lancinating pain occurs along the distribution of the trigeminal nerve, which carries sensations from your face.

In a study conducted on 12 patients with chronic intractable TN who did not respond to surgery, patients reported good-to-excellent pain relief with about 58% response rate following rTMS.

Central Poststroke Pain Syndrome

One of the most promising, off-label uses of rTMS is treating the chronic and debilitating pain that follows a stroke in 1 in every ten stroke patients. This condition is named central post-stroke pain (CPSP).

A majority of cases of CPSP are challenging and refractory to medical therapy. Thus, it’s essential to delve into other more effective yet safe treatments for CPSP, like rTMS.

An open-label study on 18 patients with CPSP showed an effective (61%) reduction in pain scores after weekly sessions of rTMS. Not only that, pain levels worsened to the levels before rTMS in almost all patients after the end of the treatment sessions. Moreover, patients who continued rTMS for one year reported long-term relief of their symptoms, underscoring the benefits of this therapy in controlling pain.

Central Pain after Traumatic Brain Injury (TBI)

Chronic central pain can also occur following TBI.

2018 clinical trial studied the effects of high-frequency rTMS on central pain after TBI. rTMS induced considerable improvement in the pain scores and quality of life of these patients following ten sessions of 10-Hz rTMS over the motor area.

Fibromyalgia (FM)

FM is another painful disorder for which TMS shows promise as an alternative therapy.

People with fibromyalgia not only endure widespread musculoskeletal pains, but they also often deal with depression. In fibromyalgia, the pain worsens depression and vice versa.

The effect of TMS on the pain levels of fibromyalgia is interesting. In six controlled trials, rTMS substantially dampened the pain response in patients with FM. Three of these trials also showed an improved quality of life in FM patients for up to 2–25 weeks after the sessions.

Another recent clinical study showed a beneficial effect of low-intensity 5-day rTMS on chronic pain levels in people with fibromyalgia. These positive effects of rTMS lasted up to 6 months in the follow-up phase.

Phantom Limb Pain (aka PLP)

PLP is a neuropathic condition manifested by a stabbing, throbbing, or burning pain in the patients’ remaining perception of an amputated limb. The state is taxing due to its negative impact on the quality of life and failure to respond to traditional treatments.

Moreover, maladaptive plasticity has been associated with PLP. Because rTMS can alter the plasticity of the affected brain areas, its use can improve the traumatic symptoms of PLP.

According to a study published in The Journal of Pain, 14 days of rTMS sessions caused a significant drop in pain scores in 70% of amputees with PLP.

Low Back Pain

Low back pain (LBP) is a fairly common problem. It is considered chronic when it lasts for more than three months. In most cases, it tends to subside with acute pain-relieving strategies. However, if it becomes chronic, LBP can take a heavy toll on the quality of life of the affected person.

According to the literature review, changes in postural and trunk muscles may lead to LBP. The primary motor area of the brain is thought to play a role in controlling these muscles. Hence, stimulating this area via TMS can benefit patients with LBP.

In a clinical trial on patients with LBP, there was an 80% reduction in pain from baseline in those who received high-intensity rTMS stimulation over the primary motor area. Two other case studies also showed that rTMS sessions minimized pain in patients with chronic LBP and depression.