Nonpainful remote electrical stimulation alleviates episodic migraine pain

Yarnitsky D, Volokh L, Ironi A, Weller B, Shor M, Shifrin A, Granovsky Y.

Nonpainful remote electrical stimulation alleviates episodic migraine pain.

Neurology. 2017 Mar 1. pii: 10.1212/WNL.0000000000003760. doi:

10.1212/WNL.0000000000003760. [Epub ahead of print]

Abstract

OBJECTIVE:

To evaluate the efficacy of remote nonpainful electrical upper arm skin stimulation in reducing migraine attack pain.

METHODS:

This is a prospective, double-blinded, randomized, crossover, sham-controlled trial. Migraineurs applied skin electrodes to the upper arm soon after attack onset for 20 minutes, at various pulse widths, and refrained from medications for 2 hours. Patients were asked to use the device for up to 20 attacks.

RESULTS:

In 71 patients (299 treatments) with evaluable data, 50% pain reduction was obtained for 64% of participants based on best of 200-μs, 150-μs, and 100-μs pulse width stimuli per individual vs 26% for sham stimuli. Greater pain reduction was found for active stimulation vs placebo; for those starting at severe or moderate pain, reduction (1) to mild or no pain occurred in 58% (25/43) of participants (66/134 treatments) for the 200-μs stimulation protocol and 24% (4/17; 8/29 treatments) for placebo (p = 0.02), and (2) to no pain occurred in 30% (13/43) of participants (37/134 treatments) and 6% (1/17; 5/29 treatments), respectively (p = 0.004). Earlier application of the treatment, within 20 minutes of attack onset, yielded better results: 46.7% pain reduction as opposed to 24.9% reduction when started later (p = 0.02).

CONCLUSION:

Nonpainful remote skin stimulation can significantly reduce migraine pain, especially when applied early in an attack. This is presumably by activating descending inhibition pathways via the conditioned pain modulation effect. This treatment may be proposed as an attractive nonpharmacologic, easy to use, adverse event free, and inexpensive tool to reduce migraine pain.

CLINICALTRIALSGOV IDENTIFIER:

NCT02453399.

CLASSIFICATION OF EVIDENCE:

This study provides Class III evidence that for patients with an acute migraine headache, remote nonpainful electrical stimulation on the upper arm skin reduces migraine pain.

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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.)…

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…

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.)…

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.”

http://journals.lww.com/neurotodayonline/Fulltext/2017/03160/Non_Invasive_Stimulation_Found_Effective_for.3.aspx