Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model

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; howev...

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Bibliographic Details
Published in:Journal of headache and pain 2022-01, Vol.23 (1), p.12-12, Article 12
Main Authors: Liu, Tzu-Ting, Morais, Andreia, Takizawa, Tsubasa, Mulder, Inge, Simon, Bruce J., Chen, Shih-Pin, Wang, Shuu-Jiun, Ayata, Cenk, Yen, Jiin-Cherng
Format: Article
Language:English
Subjects:
Animals
c-Fos protein
Calcitonin
Calcitonin gene-related peptide
Cortical Spreading Depression
Cyclooxygenase-2
Ganglia
Headache
Immunohistochemistry
Inflammation
Internal Medicine
Medicine
Medicine & Public Health
Mental depression
Migraine
Migraine Disorders - therapy
Neuroinflammation
Neuroinflammatory Diseases
Neurology
Pain Medicine
Potassium chloride
Rats
Research Article
Translational Research in Headache
Trigeminal activation
Trigeminal ganglion
Vagus nerve
Vagus Nerve Stimulation
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Summary: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 min 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 min prior to CSD. The optimal nVNS also attenuated CSD-induced upregulation of cortical cyclooxygenase-2, calcitonin gene-related peptide in trigeminal ganglia, and c-Fos expression in trigeminal nucleus caudalis. Conclusions 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.
ISSN:1129-2369
1129-2377
DOI:10.1186/s10194-022-01384-1