ARTICLE IN BRIEF
A new study found Class III evidence that remote non-invasive electrical stimulation was effective in 71 patients with acute migraine headache.
A non-invasive, electrical stimulation device significantly reduced or halted migraine pain, according to a study published in the March 1 online issue of Neurology.
The stimulating device (Nerivio Migra made by Theranica Ltd. in Netanya, Israel) is discrete and portable, consisting of a pair of rubber electrodes mounted on an armband with a power source that is controlled by the user's smartphone using a custom-made phone app. It appears to work on the central nervous system and inhibit pain perception.
“Unlike the currently approved non-drug treatments, the stimulation does not have to be local. There are no wires, only electrodes that are put on the skin of the arm that are battery operated and controlled by a phone app,” said David Yarnitsky, MD, director of the department of neurology, who led the trial with colleagues at the Rambam Healthcare Campus and Technion Faculty of Medicine in Haifa, Israel. “We believe they actually activate the endogenous analgesic system to inhibit pain and prevent the migraine attack from developing.”
The built-in endogenous analgesia system, he explained, “serves in inhibiting incoming pain messages, as part of our ability to cope with pain. This system can be activated by many factors, in either a ‘top down’ manner, by various brain structures, or ‘bottom up’ by stimuli from remote body parts. The latter is the basis of the well-known ‘pain inhibits pain’ phenomenon, which is explored in the clinical lab by one ‘conditioning’ pain inhibiting another ‘test’ pain. It has recently been described that the conditioning stimulus can be at an intensity just below pain threshold, and does not have to be painful.”
The analgesia produced by this phenomenon is limited, Dr. Yarnitsky continued, so it will not work on intense, ongoing pain syndromes. However, with migraine, there is a “golden window” in the beginning of the attack when pain is still low and full sensitization has not occurred. “This is the basis of applying the remote non-painful stimulus to alleviate migraine.”
The study provides Class III evidence (evidence from a controlled trial in a representative population, where outcome is independently assessed, or independently derived by objective outcome measurement) that remote non-invasive electrical stimulation was effective in patients with acute migraine headache, he said.
The most satisfying finding from the study, Dr. Yarnitsky told Neurology Today, was that people who used the device early enough found it to be as effective as the use of triptans for migraine. (Dr. Yarnitsky serves on the medical advisory board of Theranica Ltd., which makes the stimulating device.)
STUDY PROTOCOLS, RESULTS
This prospective, double-blinded, randomized, cross-over, and sham-controlled trial looked at treatments of 71 patients with acute migraine. The migraineurs applied skin electrodes to their upper arm for 20 minutes (with pulse widths varying between 200, 150 and 100 μsec) early in their migraine attack and did not take any medications for two hours. They were told to do this for up to 20 migraine attacks. Using their smartphone, patients were instructed to adjust the stimulus “to a well perceived, but not painful level, and readjust along the stimulation period.”
Patients also self-reported time and pain levels at onset, 10, 20 and 120 minutes after stimulation onset on a numeric 0-10 Pain Scale (NPS) on their smartphones. Researchers conducted two follow-up phone interviews with each patient, two weeks and two months into the experiment, to gather feedback regarding treatment perception, adverse effects, and use of migraine medications.
Dr. Yarnitsky and colleagues found that 64 percent of the patients using active stimulation reported a 50 percent reduction in pain, compared with 26 percent of patients using the sham stimuli. Those who initially had severe or moderate pain reported that they experienced mild or no pain 58 percent of the time (25/43 participants or 66/134 treatments) for the 200 μsec stimulation protocol, compared with 24 percent (4/17; 8/29 treatments) for placebo (p=0.02).
The earlier the application, the more effective the treatment, Dr. Yarnitsky and colleagues noted, adding that those who used the device within 20 minutes of migraine onset experienced a 46.7 percent pain reduction as opposed to 24.9 percent reduction when started later (p=0.02). No adverse events were reported by the participants.
“Migraine is a cyclical pain syndrome, where it takes a few hours to develop full sensitization of pain systems, so it is an ideal candidate for this type of pain modulation therapy,” Dr. Yarnitsky told Neurology Today.
Future studies, he said, will help determine the most effective parameters for stimulation and verify pain reduction in a larger group of patients. “We still need to test whether this is effective and safe in patients who are pregnant or breastfeeding, but we suspect that this should be the case.” Additionally, Dr. Yarnitsky said, “we would like to see if this works on other types of headaches, such as tension and cluster headaches, as well as in patients who are already taking preventative migraine medications.” The researchers are about to start a pivotal multi-center study in the US.
MIGRAINE EXPERTS RESPOND
Experts said the study findings were “very interesting,” but noted that larger trials were needed to test the device. Stephen S. Silberstein, MD, FAAN, professor of neurology and director of the headache clinic at Thomas Jefferson University Hospital in Philadelphia, told Neurology Today: “Unlike other approved non-drug devices, such as Cefaly and transcranial magnetic stimulators, this device stimulates nerves by turning off the pain perception in the brain. You can control it with your cell phone, and if the pain comes back you can turn it back on again. And unlike a triptan patch, which can be hundreds of dollars, this will likely be relatively inexpensive because much of the technology is already in your phone.” (Dr. Silberstein disclosed that he has consulted on this project in the past.)
Dr. Silberstein noted that the trial was small and it will need to be replicated in a larger number of patients, but, he added, the results so far are promising. “I think it's going to be a very interesting new adjunct for people with migraines that will not be terribly expensive.”
Dawn C. Buse, PhD, director of behavioral medicine for the Montefiore Headache Center and associate professor in the department of neurology of Albert Einstein College of Medicine, noted that electrical and magnetic stimulation of the nervous system is proving to be a valuable therapeutic approach for many reasons. “In the case of migraine, there are several approved electrical stimulation modalities with a range of reported efficacy. Unlike most electrical stimulation treatments currently approved for or being tested for the prevention of migraine, the therapy in this study is tested as an acute treatment with recommendations for use as early as possible in the beginning of a migraine attack,” she told Neurology Today.
The strengths of this trial, she said, include its prospective, double-blinded, randomized, cross-over, and sham-controlled design. Although the authors note that the blinding may not have been complete, they also point to the fact that “the observed difference between the groups may have been attenuated by this rather than enhanced by it,” said Dr. Buse.
However, she said that she would like to see imaging studies to fully understand and verify the mechanism of action of this therapy. “The authors propose that pain relief stems from ‘activating descending inhibition pathways, via the conditioned pain modulation effect.’ It is a limitation that the study did not conduct imaging or provide neurophysiological based proof that this was the underlying mechanism,'” Dr. Buse told Neurology Today.
Both experts agreed that there is a growing need for more non-pharmaceutical options for patients with migraine. “These treatment options can usually be combined with pharmacologic treatments, behavioral and physical treatments, or be used independently. They are good options for people who cannot tolerate or want or need to avoid pharmaceutical therapy for a range of reasons. It would be valuable to determine the safety of these treatments for women who are pregnant, trying to get pregnant or breastfeeding,” Dr. Buse said. “More safe and effective treatment options are needed for women of child bearing potential who comprise a sizable proportion of the total migraine population.”