Non-invasive vagus nerve stimulation for primary headache: A clinical update

Abstract

Background Non-invasive vagus nerve stimulation (nVNS) is a proven treatment for cluster headache and migraine. Several possible mechanisms of action by which nVNS mitigates headache have been identified. Methods We conducted a narrative review of recent scientific and clinical research into nVNS for headache, including findings from mechanistic studies and their possible relationships to the clinical effects of nVNS. Results Findings from animal and human studies have provided possible mechanistic explanations for nVNS efficacy in headache involving four core areas: Autonomic nervous system functions; cortical spreading depression inhibition; neurotransmitter regulation; and nociceptive modulation. We discuss how overlap and interplay among these areas may underlie the utility of nVNS in the context of clinical evidence supporting its safety and efficacy as acute and preventive therapy for both cluster headache and migraine. Possible future nVNS applications are also discussed. Conclusion Significant progress over the past several years has yielded valuable mechanistic and clinical evidence that, combined with the excellent safety and tolerability profile of nVNS, suggests that it should be considered a first-line treatment for both acute and preventive treatment of cluster headache, an effective option for acute treatment of migraine, and a highly relevant, practical option for migraine prevention.

Non-invasive vagus nerve stimulation for prevention of migraine: The multicenter, randomized, double-blind, sham-controlled PREMIUM II trial

“…Consistent with previous research (4), in PREMIUM II the migraine with aura subgroup had a more pronounced response than those without aura and appear to be particularly well suited to nVNS therapy. This clinical finding is consistent with mechanistic data from animal models, which suggest that nVNS inhibits susceptibility to and diminishes the frequency and propagation speed of cortical spreading depression, an electrophysiological phenomenon that is believed to be a major mechanism behind migraine aura (15,23,24). There is an opportunity for future research and analysis to determine whether the more prominent response of nVNS among patients with aura in this study is appreciated in other clinical settings.…”

Human organ donor-derived vagus nerve biopsies allow for well-preserved ultrastructure and high-resolution mapping of myelinated and unmyelinated fibers

“…Vagus nerve stimulation (VNS) has emerged as a neuromodulation strategy to provide an adjunctive therapy for medication-refractory epilepsy 1 , 2 and treatment-resistant depression 3 , 4 . Non-invasive approaches to electrically stimulate the vagus nerve have more recently emerged as an additional treatment strategy for migraine and cluster headache pain 5 , 6 . VNS may also inhibit cytokine production and modulate inflammatory conditions 7 .…”

Music and low-frequency vibrations for the treatment of chronic musculoskeletal pain in elderly: A pilot study

“…Although there is consensus that VNS affects pain processing, it remains unclear how this happens exactly [ 15 , 16 ]. In the last decades, traditional VNS is gradually being replaced by safer t-VNS, but t-VNS is predominantly applied in the treatment of headache, epilepsy and depression disorders [ 17 , 57 ]. Literature about the effect of electrical t-VNS on nociception is conflicting: while one study found an increase in pressure pain threshold and a decrease in reported pain ratings after an hour of transcutaneous stimulation of the auricular branch of the vagal nerve, another found that only most participants showed an increase in pain threshold after 30 minutes of similar stimulation [ 23 , 24 ].…”