Efficacy and mode of action of external trigeminal neurostimulation in migraine

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

Transcranial direct current stimulation

Migraine is the most prevalent neurological disorder worldwide; nevertheless, its pathophysiology is not yet completely understood. Recent scientific progresses in migraine research disclosed new possible targets for novel non-pharmacological treatment strategies for migraine treatment, such as noninvasive neuromodulation methods. Among them, transcranial direct current stimulation (tDCS) gave promising results in pilot studies. tDCS is a noninvasive, safe, and relatively not expensive technique of cortical electrical stimulation, aimed to modulate cortical activity in many ways, according to the stimulated sites and the polarity used. Unfortunately, large sham-controlled trials are not yet available to confirm its potential use as a preventative treatment for migraine

External trigeminal nerve stimulation

Besides having incomplete efficacy, acute and preventive migraine drug treatments have minor and major contraindications and side effects, frequently leading to patients’ dissatisfaction and treatment discontinuation. There is thus a need to explore new therapeutic approaches that have a better efficacy over side effect profile. Targeting different pathophysiological aspects, many nondrug treatments have been tested in migraine. Among them, noninvasive peripheral neurostimulation of the first division of the trigeminal nerve—central cornerstone to the initiation and maintenance of migraine pain and associated symptoms—has attracted much attention recently. A transcutaneous external trigeminal nerve stimulation (eTNS) device called Cefaly®, developed and marketed by Cefaly Technology (Seraing, Liège, Belgium), has been approved for the acute and preventive treatment of migraine by the American Food and Drug Administration. In a sham-controlled, double-blind randomized trial (the PREMICE trial), the efficacy of eTNS with Cefaly® was found to be comparable to that of prophylactic pharmacotherapies. More recently, eTNS was also proven to be effective as abortive therapy. Possible mechanisms of action through which the device induces clinical improvement in migraine include short-term effects on the peripheral and long-term effects the central nervous system