Mechanism of action of electroCore’s non-invasive vagus nerve stimulation therapy published in the Journal of Pain


In a paper published in the Journal of Pain, it was reported that electroCore’s non-invasive vagus nerve stimulation (nVNS) therapy can significantly reduce excessive glutamate levels in key regions of the central nervous system of animals sensitised to experience migraine-like symptoms.

The author of the paper, associate professor Michael Oshinsky, at Thomas Jefferson University, USA, says, “These experiments suggest a rational mechanism of action for nVNS that improves our understanding of why nVNS may be an effective treatment for headache and trigeminal allodynia (facial pain) in humans.”



The researchers used GTN, a well-known headache trigger used in animal models of headache and in human volunteer studies of migraine, to cause a significant increase in pain symptoms among the sensitised animals, but not among naïve animals.  The enhanced pain experienced in the first group was further correlated with an 8-fold increase in glutamate expression in the trigeminal nucleus caudalis, consistent with prior studies of GTN effects in this model. The study showed that when 60-seconds of nVNS treatment was given contemporaneous with the administration of GTN, the expected 8-fold increase in glutamate levels was entirely suppressed, and levels were indistinguishable from levels in the naïve animals (controls). The study further found that if the nVNS treatment was delayed for 90 minutes after the GTN administration, after glutamate levels had already begun to rise significantly, the therapy was highly effective in reducing the glutamate expression within 30 minutes. It is believed that this is more consistent with how naturally occurring migraines would be treated in humans.


Oshinsky continued, “The behavioural portion of this study reflects the clinical observations and reinforces that non-invasive vagus nerve stimulation is effective in reducing glutamate and would suggest that it has potential as a safe treatment for pain and migraine.”


electroCore chief executive officer, JP Errico, comments, “We continue to be encouraged by the research conducted by Professor Oshinsky, and others, that supports our thesis that nVNS modulates key neurotransmitters within the central nervous system. We look forward to continuing this basic science, alongside our extensive clinical efforts, to explain how the enhancement of inhibitory neurotransmitters, and the suppression of excitatory neurotransmitters, like glutamate, shown in this study, has a beneficial effect on conditions, like headache, in which the symptoms experienced by sufferers are related to an imbalance of these neurotransmitters.”