Key result
Two 2-minute noninvasive vagus nerve stimulations delivered 5 minutes apart increased the electrical cortical spreading depression threshold by 68% and reduced its frequency by 24%.
Why the study?
Noninvasive vagus nerve stimulation emerged as a promising migraine therapy that inhibits cortical spreading depression, but the optimal stimulation paradigm had not been defined.
Does noninvasive vagus nerve stimulation reduce cortical spreading depression susceptibility and neuroinflammation in a rat model?
Does noninvasive vagus nerve stimulation reduce cortical spreading depression susceptibility and neuroinflammation in a rat model?
Effect estimate: 68% higher electrical CSD threshold and 24% lower KCl-induced CSD frequency
Noninvasive vagus nerve stimulation suppresses cortical spreading depression susceptibility and associated neuroinflammation in an intensity-dependent manner, with two 2-minute stimulations providing optimal efficacy.
Animal nVNS optimization data should not yet change migraine practice; leaves open optimal dosing for clinical translation.
Background Noninvasive vagus nerve stimulation (nVNS) has recently emerged as a promising therapy for migraine. We previously demonstrated that vagus nerve stimulation inhibits cortical spreading depression (CSD), the electrophysiological event underlying migraine aura and triggering headache; however, the optimal nVNS paradigm has not been defined. Methods Various intensities and doses of nVNS were tested to improve efficacy on KCl-evoked CSD frequency and electrical threshold of CSD in a validated rat model. Chronic efficacy was evaluated by daily nVNS delivery for four weeks. We also examined the effects of nVNS on neuroinflammation and trigeminovascular activation by western blot and immunohistochemistry. Results nVNS suppressed susceptibility to CSD in an intensity-dependent manner. Two 2-minute nVNS 5 minutes apart afforded the highest efficacy on electrical CSD threshold and frequency of KCl-evoked CSD. Daily nVNS for four weeks did not further enhance efficacy over a single nVNS 20 minutes prior to CSD. The optimal nVNS also attenuated CSD-induced upregulation of cortical cycloogenase-2, calcitonin gene-related peptide in trigeminal ganglia, and c-Fos expression in trigeminal nucleus caudalis. Conclusion Our study provides insight on optimal nVNS parameters to suppress CSD and suggests its benefit on CSD-induced neuroinflammation and trigeminovascular activation in migraine treatment.
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Liu et al. (2021) studied Cortical spreading depression (Migraine model) (n=104). Noninvasive vagus nerve stimulation (nVNS) vs. Sham stimulation or noninvasive femoral nerve stimulation (nFNS) was evaluated on Electrical CSD threshold and KCl-evoked CSD frequency (68% higher electrical CSD threshold and 24% lower KCl-induced CSD frequency). Two 2-minute noninvasive vagus nerve stimulations delivered 5 minutes apart increased the electrical cortical spreading depression threshold by 68% and reduced its frequency by 24%.
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