REN Serves as Potential Treatment Alternative for Chronic Migraine

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Results of a multicenter study suggest remote electrical neuromodulation (REN) may serve as a nonpharmaceutical treatment option for migraine.

Remote electrical neuromodulation (REN) treatments resulted in relief of migraine and associated symptoms and may serve as a drug-free acute treatment option for individuals with chronic migraine, according to results of an open-label study. Findings were published in Pain Reports.

“Treatments of chronic migraine are mainly aimed at reducing the rate of monthly migraine headaches and decreasing the disability associated with migraine without overusing acute medications to avoid the development of medication overuse headache (MOH),” researchers explained. This poses a challenge to providers as they aim to relieve attack symptoms, while simultaneously reducing acute medication use.

To meet this challenge, REN has been developed as a nonpharmaceutical acute migraine treatment. The device noninvasively stimulates upper arm peripheral nerves and “triggers an endogenic analgesic mechanism named conditioned pain modulation, in which pain in one body part is inhibited by pain in another body region,” the authors wrote.

Previous research has aimed to confirm the efficacy of REN and yielded positive results. To build on these findings, the investigators conducted an open-label, single-arm safety and efficacy study. Ninety-one patients had an evaluable treatment with REN; each session lasts 45 minutes.


All participants were between the ages 18 and 75 with a diagnosis of chronic migraine. Within 2 months prior to enrollment, participants did not use preventive medications or were on a stable dose of a preventive medication and continued it throughout the study period.

Following a 4-week run-in phase, “eligible patients continued into a 4-week treatment phase, in which they were requested to treat all migraine attacks within 1 hour of symptom onset with an individualized stimulation intensity that is just below the pain threshold. Participants were asked to refrain from the use of medications within 2 hours after treatment.” Patients recorded their symptoms at treatment initiation, 2 hours after treatment, and 24 hours after treatment.

The average number of treatments per subject was 7.3 while around 82% of participants reported a moderate to severe pain intensity at treatment initiation.

Analyses revealed:

  • Pain relief and pain disappearance at 2 hours were achieved by 59.3% (54 of 91; 95% CI, 48.5%-69.5%) and 20.9% (19 of 91; 95% CI, 13.0%-30.6%) of modified intent-to-treat subjects, respectively (with worst-case sensitivity analysis indicating 54.5% and 19.2%, respectively)
  • Sustained pain relief at 24 hours was observed in 64.4% (29 of 45) of those who achieved pain relief at 2 hours (with worst-case sensitivity analysis indicating 45.6%)
  • Nausea or vomiting, photophobia, and phonophobia disappeared at 2 hours in 48.8% (20 of 41; 95% CI, 32.8%-64.8%), 40.5% (30 of 74; 95% CI, 29.2%-52.5%), and 44.6% (29 of 65; 95% CI, 32.2%-57.4%) of participants, respectively
  • 59.4% (19 of 32; 95% CI, 40.6%-76.3%) of patients experienced improvement in functional ability at 2 hours (only subjects with functional disability at baseline were included in the analysis)
  • 57.1% (52 of 91; 95% CI, 46.3%-67.4%) of patients achieved pain relief at 2 hours in at least half of their treatments
  • 1 patient experienced a device-related adverse event in which pain in the arm was felt after the use of the device on that arm; this adverse event was mild, resolved within 24 hours without medication

“No serious device-related adverse events were reported, and no subject withdrew consent because of an adverse event,” the authors added.

Although no head-to-head trials have been conducted, data comparisons indicate the consistent response to REN is similar to that to triptans (57% for REN vs 47%-72% for triptans) and could be superior to noninvasive vagal nerve stimulation (nVNS) (57% for REN vs 47% for nVNS).

The direct effects of REN on MOH were not assessed in the current analysis, and more research is needed to better understand this association. In addition, REN treatment was not compared with a sham stimulation, marking limitationd to this analysis.

Of the 126 participants recruited to the study, only data from 91 were reflected in the dataset. However, “27 of the 35 participants were excluded in the run-in phase, in which the REN device was not yet given to the participants and was not used or tested,” the researchers said.

“This study supports the efficacy and positive benefit-to-risk ratio for REN used for the acute treatment of chronic migraine. This investigation demonstrates that REN may provide an alternative nonpharmacological acute treatment option in people with chronic migraine, holding the potential to diminish medication use in a population prone to develop MOH,” they concluded.


Grosberg B, Rabany L, Lin T, et al. Safety and efficacy of remote electrical neuromodulation for the acute treatment of chronic migraine: an open-label study. Pain Rep. Published online October 14, 2021. doi:10.1097/PR9.0000000000000966