Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model
Abstract 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 headac...
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10194-022-01384-1 |
| _version_ | 1818332910668742656 |
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| author | Tzu-Ting Liu Andreia Morais Tsubasa Takizawa Inge Mulder Bruce J. Simon Shih-Pin Chen Shuu-Jiun Wang Cenk Ayata Jiin-Cherng Yen |
| author_facet | Tzu-Ting Liu Andreia Morais Tsubasa Takizawa Inge Mulder Bruce J. Simon Shih-Pin Chen Shuu-Jiun Wang Cenk Ayata Jiin-Cherng Yen |
| author_sort | Tzu-Ting Liu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-13T13:43:15Z |
| format | Article |
| id | doaj.art-0e084bdc90a24594ba3851b9a08166c8 |
| institution | Directory Open Access Journal |
| issn | 1129-2369 1129-2377 |
| language | English |
| last_indexed | 2024-12-13T13:43:15Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-0e084bdc90a24594ba3851b9a08166c82022-12-21T23:43:31ZengBMCThe Journal of Headache and Pain1129-23691129-23772022-01-0123111310.1186/s10194-022-01384-1Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat modelTzu-Ting Liu0Andreia Morais1Tsubasa Takizawa2Inge Mulder3Bruce J. Simon4Shih-Pin Chen5Shuu-Jiun Wang6Cenk Ayata7Jiin-Cherng Yen8Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung UniversityNeurovascular Research Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical SchoolNeurovascular Research Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical SchoolNeurovascular Research Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical SchoolelectroCore, IncDepartment of Neurology, Taipei Veterans General HospitalDepartment of Neurology, Taipei Veterans General HospitalNeurovascular Research Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical SchoolInstitute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung UniversityAbstract 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.https://doi.org/10.1186/s10194-022-01384-1Cortical spreading depressionVagus nerve stimulationNeuroinflammationTrigeminal activation |
| spellingShingle | Tzu-Ting Liu Andreia Morais Tsubasa Takizawa Inge Mulder Bruce J. Simon Shih-Pin Chen Shuu-Jiun Wang Cenk Ayata Jiin-Cherng Yen Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model The Journal of Headache and Pain Cortical spreading depression Vagus nerve stimulation Neuroinflammation Trigeminal activation |
| title | Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model |
| title_full | Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model |
| title_fullStr | Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model |
| title_full_unstemmed | Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model |
| title_short | Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model |
| title_sort | efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model |
| topic | Cortical spreading depression Vagus nerve stimulation Neuroinflammation Trigeminal activation |
| url | https://doi.org/10.1186/s10194-022-01384-1 |
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