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Updated: Feb 9, 2026

Investigating Migraine-Like Behavior Using Light Aversion in Mice
Published on: August 11, 2021
Efficacy and mode of action of external trigeminal neurostimulation in migraine
Jean Schoenen1, Gianluca Coppola2
1a Headache Research Unit , University Department of Neurology CHR Citadelle Hospital , Liège , Belgium.
Introduction:
Available preventive drug treatments for migraine lack complete efficacy and often have unpleasant adverse effects. Hence, their clinical utility and therapeutic adherence are limited. Noninvasive neurostimulation methods applied over various peripheral sites (forehead, mastoid, upper arm, cervical vagus nerve) have raised great interest because of their excellent efficacy/tolerance profile. Among them external trigeminal nerve stimulation (eTNS) was first to obtain FDA approval for migraine therapy. Areas covered: All clinical trials of eTNS as preventive or acute migraine treatment published in extenso or presented at congresses are reviewed. The paper analyzes neuroimaging and neurophysiological studies on mechanisms of action of eTNS. As many of these studies point toward the anterior cingulate cortex (ACC) as a likely eTNS target, the paper scrutinizes the available literature on the ACC implication in migraine pathophysiology. Expert commentary: eTNS is a viable alternative to standard pharmacological antimigraine strategies both for prevention and abortive therapy. eTNS could chiefly exert its action by modulating the perigenual ACC, which might also be of interest for treating other disorders like fibromyalgia or depression. It remains to be determined if this might be a common mechanism to other peripheral noninvasive neurostimulation methods.
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