To explore the mechanism of action of nVNS in this same study, the research team intracisternally injected those rats exposed to CBL with the GABAA antagonist bicuculline, the 5-HT3 antagonist ondansetron, or the 5-HT7 antagonist SB-269970. 5-HT3 and 5-HT7 receptors were targeted because of the strong evidence of their involvement in descending pain modulation, explained Dr Durham in conversation with Neurology Times. “They are known to cause release of the inhibitory neurotransmitters GABA and glycine from inhibitory neurons to block ascending pain signaling.” The injection of GABAA antagonists or injection of 5-HT3 and 5-HT7 antagonists in a subset of rats did block the analgesic effect of nVNS.
The nVNS pathway differs from that of triptans, which bind to and stimulate 5-HT1B and 5-HT1D and block pain signaling neurotransmitters ascending toward the thalamus.4 “The triptans are believed to block the release of CGRP and glutamate from primary trigeminal nerves that project into the spinal cord and thus inhibit activation of second order neurons involved in the ascending pain pathway,” noted Dr Durham. The “take-home,” according to him is that “VNS provides a viable alternative therapy for episodic migraine patients that do not respond to triptans or when triptans are contraindicated,” adding that the use of nVNS may be more beneficial in patients with impaired descending pain modulation.
In addition, nVNS may have value in preventing transformed migraine if initiated early enough. “We have evidence in our lab from animal studies that daily nVNS can prevent the development of chronic trigeminal sensitization in our chronic migraine model when administered early in the transition to a more sensitized system,” said Dr Durham.
1. Cornelison LE, Woodman SE, Durham PL. Noninvasive vagus nerve stimulation inhibits trigeminal nociception in two episodic migraine models by enhancing descending pain modulation. Presented at: 61st Annual Meeting of the American Headache Society; July 11-14, 2019; Philadelphia, PA.
2. Tassorelli C, Grazzi L, de Tommaso M, et al; PRESTO Study Group. Noninvasive vagus nerve stimulation as acute therapy for migraine: the randomized PRESTO study. Neurology. 2018;91:e364-e373.
3. Grazzi L, Tassorelli C, de Tommaso M, et al; PRESTO Study Group. Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial. J Headache Pain. 2018;19:98.
4. Cortelli P, Allais G, Benedetto C. Overview of triptans in the treatment of acute migraine. Euro Neurologic Rev. 2017;12:71-77.