Efficacy of Remote Electrical Neuromodulation (REN) on Migraine-Induced Neuronal Activity: A Systematic Review

A BSTRACT This systematic review evaluated the efficacy of Remote Electrical str Neuromodulation (REN) in migraine-induced neuronal activity. A PubMed and Google Scholar search identified studies published between 2007 and 2025. Inclusion criteria focused on randomized controlled trials, open-label studies, and real-world observational studies that evaluated REN for migraine treatment. Duplicate reports and studies with insufficient information were excluded. Data extraction and quality assessment followed preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and the Newcastle-Ottawa Scale. The results showed that 10 peer-reviewed studies were included (4 Randomized Controlled Trials [RCTs], 4 open-label studies, and 2 real-world observational studies). REN demonstrated significant improvements in pain freedom and pain relief at 2 hours compared to placebo (pain freedom: 41-46% vs. 20-25%, pain relief: 59-67% vs. 35-42%). Patients treated with REN also showed significant reductions in migraine attacks and improved daily functioning. REN was well-tolerated, with minimal side effects, primarily mild local paresthesia or skin sensitivity. The majority of RCTs had low risk of bias, though observational studies exhibited a higher risk. It was concluded that REN may serve as a valuable nonpharmacologic option for migraine management.