electroCore LLC

Mechanism of Action

Novel, non-invasive vagus nerve stimulation (nVNS) with gammaCore

The therapeutic role of implanted vagus nerve stimulation is well established in several disorders related to autonomic dysfunction.1–4

In an animal model, excessive glutamate levels in the trigeminal nucleus caudalis (TNC) are believed to be a marker for increased trigeminal pain.5

In an animal model, non-invasive vagus nerve stimulation (nVNS) demonstrates the ability to suppress high glutamate levels in the TNC, which may be the mechanism by which it alleviates the symptoms of headache.5

gammaCore nVNS Mechanism of Action5


Pre-Clinical Data

An animal model of trigeminal allodynia simulating the hypersensitivity found in patients with migraine was used to examine the mechanism of action of nVNS5

nVNS increased periorbital pain threshold

  • Rats were given prostaglandin E2 infusion 3 times a week for 3 to 4 weeks to produce matching patterns of migraine pain5
  • Following 2 minutes of nVNS, periorbital pain threshold increased 4.7 ± 1.0 times within 5 minutes (vs pre-stimulation levels) and was maintained for 3.5 hours after nVNS5

nVNS decreased trigeminal nociceptive stimulation by suppressing the rise in glutamate5

  • Glyceryl trinitrate (GTN) treatment administered to allodynic rats caused a 7.7 ± 0.9-fold increase in extracellular glutamate5
  • 2 minutes of nVNS plus GTN treatment resulted in only a 2.3 ± 0.4-fold increase in extracellular glutamate in allodynic rats and was not significantly different from the glutamate increases in naïve rats after GTN (1.9 ± 0.1-fold increase)5
  • Delayed nVNS (120 minutes after GTN in allodynic rats) effected a rapid glutamate level decrease from 4.8 ± 2.4-fold to 1.9 ± 0.9-fold5


Allodynic rats that were treated with nVNS after the GTN injection reversed the increase in glutamate5

gammaCore Augmented Reality (AR) Application

This application was designed to create an interactive format to learn more about primary headaches and the proposed mechanism of action of the gammaCore® device.



Step 1: Download “Trackable” Image and view the gammaCore augmented reality instructional video

Download and print the gammaCore “trackable” image designed specifically to be scanned by the AR application. Click here.


Step 2: Download App
Download the app from the App Store. Click here to download.


Step 3: Follow App Instructions
After you launch the app, follow the on-screen instructions and point your mobile device camera at the gammaCore “trackable” image to experience the AR effect.


gammaCore: Clinical Results


1. Groves DA, Brown VJ. Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neurosci Biobehav Rev. 2005;29(3):493-500.
2. Krahl SE, Clark KB, Smith DC, Browning RA. Locus coeruleus lesions suppress the seizure- attenuating effects of vagus nerve stimulation. Epilepsia. 1998;39(7):709-714.
3. Berry SM, Broglio K, Bunker M, Jayewardene A, Olin B, Rush JA. A patient?level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression. Med Devices (Auckl). 2013; 6: 17-35.
4. Daban C, Martinez-Aran A, Cruz N, Vieta E. Safety and efficacy of Vagus Nerve Stimulation in treatment-resistant depression. A systematic review. J Affect Disord. 2008;110(1-2):1-15.
5. Oshinsky ML, Murphy AL, Hekierski H Jr., Cooper M, Simon BJ. Non-invasive vagus nerve stimulation as treatment for trigeminal allodynia. Pain (2014), doi: