• Yun Zhang, Yixin Zhang, Yanyun Wang, Xiaoyan Zhang, Guangcheng Qin, Dunke Zhang, Lixue Chen, and Jiying Zhou.
• Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yu Zhong District, Chongqing, 400016, China.
• J Headache Pain. 2023 Jun 30; 24 (1): 7777.

BackgroundPrior clinical studies suggest a shared mechanism between vestibular symptoms and migraine headache. However, the specific neuroanatomical substrate connecting vestibular symptoms with migraine remains to be largely unknown. Thus, the aim of this study was to further investigate the mechanisms that whether and how trigeminovestibular neurons produce effects on neuronal activation in vestibular nucleus (VN).MethodsA chronic-NTG rat model was established by recurrent intermittent administration of nitroglycerin (NTG). Pain- and vestibular-related behaviors were assessed. To selectively inhibit the glutamatergic neurons and trigeminal nucleus caudalis (TNC) to VN projection neurons, the AAVs encoding engineered Gi-coupled hM4D receptor were administered in the TNC or VN area.ResultsWe identify a glutamatergic projection from TNC to VN that mediates vestibular dysfunction in a chronic-NTG rat model. Inhibition of the GlutamateTNC neurons alleviates vestibular dysfunction in the chronic-NTG rat. Calcitonin gene-related peptide (CGRP)-expressing neurons in the VN received glutamatergic projections from TNC neurons. Silencing the glutamatergic TNC-VN projection neurons attenuates vestibular dysfunction in the chronic-NTG rat.ConclusionsTogether, we reveal a modulatory role of glutamatergic TNC-VN projection neurons in vestibular dysfunction of migraine.© 2023. The Author(s).

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