Vagus nerve stimulation inhibits cortical spreading depression exclusively through central mechanisms
| Autor: | Ilknur Ay, David Y. Chung, Damla Yagmur, Jiin Cherng Yen, Andreia Morais, Rubem Carlos Araújo Guedes, Tzu Ting Liu, Shih Pin Chen, Cenk Ayata, Homa Sadhegian, Rosangela Mendes Da Silva, Shuu Jiun Wang, Tao Qin, Bruce J. Simon |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Vagus Nerve Stimulation Migraine Disorders medicine.medical_treatment Stimulation Pharmacology Serotonergic Article Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine 030202 anesthesiology Animals Medicine Glutamate receptor antagonist business.industry Cortical Spreading Depression Vagus Nerve Vagotomy Rats Vagus nerve Anesthesiology and Pain Medicine Neurology chemistry Cortical spreading depression CNQX Neurology (clinical) business 030217 neurology & neurosurgery Vagus nerve stimulation |
| Zdroj: | Pain |
| ISSN: | 1872-6623 0304-3959 |
| Popis: | Experimental and clinical data strongly support vagus nerve stimulation (VNS) as a novel treatment in migraine. Vagus nerve stimulation acutely suppresses cortical spreading depression (CSD) susceptibility, an experimental model that has been used to screen for migraine therapies. However, mechanisms underlying VNS efficacy on CSD are unknown. Here, we interrogated the central and peripheral mechanisms using VNS delivered either invasively (iVNS) or noninvasively (nVNS) in male Sprague-Dawley rats. Cortical spreading depression susceptibility was evaluated 40 minutes after the stimulation. iVNS elevated the electrical CSD threshold more than 2-fold and decreased KCl-induced CSD frequency by 22% when delivered to intact vagus nerve. Distal vagotomy did not alter iVNS efficacy (2-fold higher threshold and 19% lower frequency in iVNS vs sham). By contrast, proximal vagotomy completely abolished iVNS effect on CSD. Pharmacological blockade of nucleus tractus solitarius, the main relay for vagal afferents, by lidocaine or glutamate receptor antagonist CNQX also prevented CSD suppression by nVNS. Supporting a role for both norepinephrine and serotonin, CSD suppression by nVNS was inhibited by more than 50% after abrogating norepinephrinergic or serotonergic neurotransmission alone using specific neurotoxins; abrogating both completely blocked the nVNS effect. Our results suggest that VNS inhibits CSD through central afferents relaying in nucleus tractus solitarius and projecting to subcortical neuromodulatory centers providing serotonergic and norepinephrinergic innervation to the cortex. |
| Databáze: | OpenAIRE |
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