Nonpainful remote electrical stimulation alleviates episodic migraine pain

Yarnitsky, David; Volokh, Lana; Ironi, Alon; Weller, Boaz; Shor, Merav; Shifrin, Alla; Granovsky, Yelena

doi:10.1212/wnl.0000000000003760

Cited by 88 publications

(67 citation statements)

References 31 publications

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“…The device is applied for 45 minutes on the lateral upper arm between the bellies of the lateral deltoid triceps, so that it will mainly stimulate small skin nerves. The rationale for stimulating the arm and the underlying mechanism of action are described in details elsewere . The active device produces a proprietary electrical signal comprising a modulated symmetrical biphasic square pulse with a modulated frequency of 100‐120 Hz, pulse width of 400 μs, and output current up to 40 mA (adjusted by the participant).…”

Section: Methodsmentioning

confidence: 99%

“…The sham device differed from the active device in the pulse frequency which was ~0.083 Hz and the pulse width which was 40‐550 μs (modulated), aimed to induce a solid and perceptible sensation similar to the active device, but with a sufficient low frequency to prevent any modulation of nociceptive processes. The parameters of the sham and active devices were chosen following a pilot study which used several stimulation programs in a crossover design . The stimulation intensity of both the active and sham devices was adjusted by the users using the app.…”

Section: Methodsmentioning

confidence: 99%

“…Remote electrical neuromodulation (REN) is a novel acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation (CPM) – an endogenous analgesia mechanism in which conditioning stimulation inhibits pain in remote body regions . The mechanism of REN and its potential use in migraine have been described in details in a recent pilot study . Presumably, REN activates descending inhibition pathways that originate in the periaqueductal gray (PAG) and in the rostral ventromedial medulla (RVM) which globally inhibit pain by the release of serotonin and noradrenalin (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…). The pilot study demonstrated that early treatment of migraine attacks with REN can significantly reduce headache . In this paper, we report the results of a randomized, double‐blind, sham‐controlled, multicenter pivotal study designed to evaluate the efficacy and safety of REN for the acute treatment of migraine.…”

Section: Introductionmentioning

confidence: 99%

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Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial

et al. 2019

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Objective To assess the efficacy and safety of a remote electrical neuromodulation (REN) device for the acute treatment of migraine. Background There is a significant unmet need for novel effective well‐tolerated acute migraine treatments. REN is a novel acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation – an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. A recent pilot study showed that REN can significantly reduce headache. We have conducted a randomized, double‐blind, sham‐controlled study to further evaluate the efficacy and safety of REN for the acute treatment of migraine. Methods This was a randomized, double‐blind, sham‐controlled, multicenter study conducted at 7 sites in the United States and 5 sites in Israel. Two hundred and fifty‐two adults meeting the International Classification of Headache Disorders criteria for migraine with 2‐8 migraine headaches per month were randomized in a 1:1 ratio to active or sham stimulation. A smartphone‐controlled wireless device was applied for 30‐45 minutes on the upper arm within 1 hour of attack onset; electrical stimulation was at a perceptible but non‐painful intensity level. Migraine pain levels were recorded at baseline, 2, and 48 hours post‐treatment. Most bothersome symptoms (MBS) were also recorded. The primary efficacy endpoint was the proportion of participants achieving pain relief at 2 hours post‐treatment (improvement from severe or moderate pain to mild or none, or from mild pain to none). Relief of MBS and pain‐free at 2 hours were key secondary endpoints. Results Active stimulation was more effective than sham stimulation in achieving pain relief (66.7% [66/99] vs 38.8% [40/103]; therapeutic gain of 27.9% [CI95%, 15.6‐40.2]; P < .0001), pain‐free (37.4% vs 18.4%, P = .003), and MBS relief (46.3% vs 22.2%, P = .0008) at 2 hours post‐treatment. The pain relief and pain‐free superiority of the active treatment was sustained 48 hours post‐treatment. The incidence of device‐related adverse events was low and similar between treatment groups (4.8% [6/126] vs 2.4% [3/126], P = .499). Conclusions REN provides superior clinically meaningful relief of migraine pain and MBS compared to placebo, offering a safe and effective non‐pharmacological alternative for acute migraine treatment.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial

et al. 2019

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“…In their article "Nonpainful remote electrical stimulation alleviates episodic migraine pain," Dr. Yarnitsky et al 1 investigated the use of nonpainful electrical stimulation of the skin of the arm in reducing migraine attacks. Therapeutic electrical stimulation has been widely used for pain treatment.…”

Section: Migraine Reliefmentioning

confidence: 99%

Migraine relief

Monteith¹

2017

Neurology

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Acute Treatments for Episodic Migraine in Adults

VanderPluym

Singh

Urtecho

et al. 2021

JAMA

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IMPORTANCEMigraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy.OBJECTIVE To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults.DATA SOURCES Multiple databases from database inception to February 24, 2021.STUDY SELECTION Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks.DATA EXTRACTION AND SYNTHESIS Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small. MAIN OUTCOMES AND MEASURESThe main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews.FINDINGS Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT 1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham.CONCLUSIONS AND RELEVANCE There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.

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Nonpainful remote electrical stimulation alleviates episodic migraine pain

Abstract: 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.

Cited by 88 publications

References 31 publications

Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial

Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial

Migraine relief

Acute Treatments for Episodic Migraine in Adults

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