Using magnetic fields to treat the brain sounds more than a bit woo-woo. The brain, though, is an electrical organ. Our central nervous system uses tiny bits of electricity – electrons – to send signals whizzing around the brain, and electrons in turn create magnetic fields, which in turn, can alter electrical currents.
Transcranial magnetic stimulation (TMS or repetitive magnetic stimulation – rTMS) produces brief magnetic pulses which alter the electrical currents in the brain. At first TMS was used in behavioral disorders like depression, but over time it’s come to be used in other central nervous system disorders.
TMS has been used to reduce depression and fatigue in multiple sclerosis and TMS significantly reduced episodes of “freezing” in which people with Parkinson’s Disease find them themselves unable to move. TMS appeared to be able to do this by increasing connectivity between the supplementary motor (e.g. movement) area and other parts of the brain.
Studies suggest that increased activity in the dorsolateral prefrontal cortex and orbitofrontal cortices is associated with increased pain. As the prefrontal cortex is a higher brain organ and is the seat of executive functioning (i.e. rational thought, planning, creativity, working memory, etc.), it seems surprising that increased activity there would result in more rather than less pain.
The brain is a complex organ, however, and the dorsolateral prefrontal cortex (DLPFC) is not only involved in pain control but also pain detection. Activity in the left side of the DLPFC has been associated with increased sensations of the unpleasantness side of pain. (The sensation of pain unpleasantness is distinct from the sensation of pain.) Increased DLFPC activity has also been associated with allodynia – a common problem in FM.
It’s possible that both pain activation and pain inhibition are regulated by the DLPFC. Activating one DLPFC circuit appears to result in increased pain catastrophizing and an intensification of pain, while activating another circuit results in increased pain control and reduced pain.
The Fibromyalgia TMS Study
Low or high frequency TMS can be used. While low frequency TMS generally results in reduced brain activity, high frequency TMS produces increased brain activity.
Figuring that the DLPFC in FM patients’ brains were already too active, this fibromyalgia study used low frequency TMS. It was hoped that calming the fires in the DLPFC would translate into reduced activity in other brain organs involved in pain production including the thalamus, brainstem, insular and cingulate cortices.
TMS was delivered over the right DLPFC of 45 FM patients for 27 minutes a day for 5 consecutive days/weekly for 4 weeks. (A sham TMS protocol was delivered to 45 more FM patients.) The patients were followed for a full six months – an exceptionally long time for a study like this – to see if the effects were long lasting.
The primary outcome of the study was something called the Numerical Pain Rating Scale (NPRS) which assesses pain on a 1-10 scale (1=no pain; 10=worst possible pain).
Using a magnet to calm the electrical signals in the DLPFC worked. The FM patients getting the electrical signals in their brains gently rearranged received quite significant pain benefits.
At the beginning of the study, both the sham TMS and the real TMS participants rated their pain at about a dauntingly high 7.5/10. From there the pain levels of the two groups diverged markedly. Those given the real TMS rated their pain at approximately a 3/10 while those given the sham TMS dropped a bit but still remained high (@ 7/10). Remarkably, the pain levels of those given the real TMS treatment remained low six months after the treatments had ended.
Pain-related depression and anxiety were also significantly reduced in those given the real TMS treatments.
Objective Evidence of Reduced Pain Sensitivity
The researchers also provided an objective assessment of pain using something called the nociceptive flexion response (NFR). There’s no other way to objectively assess pain without causing it, and that’s just what they did.
NFR is assessed by electrically stimulating a nerve in the biceps femoris muscle in the thigh. The test assessed the degree to which that muscle jumps in response to the painful stimulation. The magnitude of the reflex is related to the intensity of the pain evoked.
The researchers only did this test once 15 days after the TMS sessions had concluded. The biceps muscle of those getting the real TMS treatment was much less sensitive to the electrical stimulation (i.e. jumped at a higher level of stimulation.)
- Transcranial magnetic stimulation (TMS or rTMS) is a way of using a magnetic coil to alter the electrical impulses – aka the activity of the brain.
- TMS was first attempted in depression, but is now being tried in a variety of other illnesses including chronic pain states such as neuropathic pain, migraine and fibromyalgia as well as multiple sclerosis and Parkinson’s disease.
- This study used low frequency TMS to calm down the activity of the right dorsolateral prefrontal cortex – an area of the brain which has been associated with chronic pain.
- They hoped that calming down this area of the brain would calm down pain producing areas of the brain known to be upregulated in FM such as the insula and anterior cingulate cortex.
- Half of the participants received TMS five days a week for a month for about 30 minutes at a time. The other half of the participants received a sham treatment. They were then tracked for an unusually long period of time – six months.
- The study found that the FM patients getting the TMS treatment were in significantly less pain – dropping from about 7.5 on a pain scale to about a 3.5 throughout the six month study period. They also reported less depression and anxiety. Those getting the sham treatment remained about the same.
- The study also used an objective test using electrical currents to show that the FM patient’s pain producing system had calmed down.
- TMS results in FM have been mixed, with more studies showing positive effects. The variety of approaches the studies have used (low vs high frequency, aiming the TMS at different parts of the brain) have made it difficult to derive conclusions regarding the treatment’s effectiveness.
- A recent overview, however, stated there was probable efficacy for using high frequency rTMS on the left M1 (motor cortex) or left DLPFC in fibromyalgia. (This study used low frequency on the right DLPFC).
- Insurance reportedly does not cover TMS for fibromyalgia.
- Next up – could TMS help with the fatigue in FM or ME/CFS?
Nobody is exactly sure how TMS does what it does, but the authors believed the stimulation probably reduced blood flows between regions of the brain involved in producing pain. Several studies have found increased connectivity between the pain producing regions of the brain in FM.
Unfortunately, while TMS Advantage website recommends TMS for FM, it states that insurance does not cover TMS for fibromyalgia.
This study was noteworthy because it suggested that the effects of TMS, if done intensively over a month or so, may be long lasting – something the insurance companies might find helpful.
Field in Flux
Of the 10 TMS randomized control trials in FM (including this latest one), seven have had positive results. A 2017 meta-analysis, however, did not find that rTMS produced clinically meaningful reductions in pain. A 2016 meta-analysis found significant improvements in quality of life and a trend toward reducing pain. That review highlighted a key issue: the need to determine “optimal treatment protocols.”
The field is plagued by an abundance of variability. Studies have not consistently used the same frequency or aimed at the same areas of the brain. In contrast to this recent study, most studies have used high-frequency or stimulating TMS aimed at different areas of the brain such as the motor cortex or the left dorsolateral prefrontal cortex (DLPFC) (three studies).
The last FM study to employ the kind of low frequency stimulation used in this current study occurred in 2013. It produced significant reduction in pain thresholds, increased ability to perform daily activities, decreased perceived chronic pain and increased sleep quality.
Another approach concerns the use of multi-coil (as opposed to single-coil) magnetic stimulation to reach the deeper parts of the brain. A 2013 study found this approach significantly reduced pain for at least four weeks following the 20 rTMS sessions.
A European Commission recently published “Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)” on a variety of conditions. They concluded that there was Level B evidence (of probable efficacy) for using high frequency rTMS on the left M1 (motor cortex) or DLPFC in fibromyalgia.
It should be noted that rTMS or TMS is just one of several non-invasive stimulatory techniques being attempted. Others include transcutaneous electrical nerve stimulation (TENS), transcranial direct current stimulation (tDCS), remote electrical neuromodulation (REN) and vagus nerve stimulation (VNS).
With brain stimulation techniques becoming more refined, and with the NIH’s SPARC initiative (Stimulating Peripheral Activity to Relieve Conditions) taking a deep dive into the nerves in the bod, it’s possible that over time we will see more and more effective ways of non-invasively and safely modulating the bodies electrical fields for better health.
This study suggested that TMS can significantly reduce pain as well as anxiety and depression – but what about fatigue? If TMS can reduce pain in some people, could it also affect the fatigue in ME/CFS and other diseases? A blog on that is coming up shortly.
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