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Poster

Calcitonin gene-related peptide receptor antagonist BIBN4096BS regulates synaptic transmission in the vestibular nucleus and improves vestibular function via PKC/ERK/CREB pathway in an experimental chronic migraine rat model

Beitrag in

Poster session 1

Posterthemen

Migraine

Basic science, animal models in headache research

Mitwirkende

Ruimin Tian (Chongqing/ CN), Yun Zhang (Chongqing/ CN), Qi Pan (Chongqing/ CN), Yunfeng Wang (Chongqing/ CN), Qianwen Wen (Chongqing/ CN), Xiaoping Fan (Chongqing/ CN), Guangcheng Qin (Chongqing/ CN), Dunke Zhang (Chongqing/ CN), Lixue Chen (Chongqing/ CN), Yixin Zhang (Chongqing/ CN), Jiying Zhou (Chongqing/ CN)

Abstract

Abstract text (incl. figure legends and references)

Questions: Vestibular symptoms are frequently reported in patients with chronic migraine (CM). The neuropeptide calcitonin gene-related peptide (CGRP) and CGRP1 receptor are essential to facilitate central sensitization in CM. However, the role of CGRP/CGRP1 receptor signaling in vestibular dysfunction after CM remains unclear.

Methods: A CM rat model was established by recurrent intermittent administration of nitroglycerin. Migraine- and vestibular-related behaviors were assessed. BIBN4096BS and protein kinase C (PKC) inhibitor-chelerythrine chloride were administered intracerebroventricularly. The expressions of CGRP and CGRP1 receptor components in the vestibular nucleus (VN) were evaluated. Synaptic associated proteins and synaptic morphological characteristics were explored. The expressions of down-stream molecules including PKC, phosphorylated extracellular signal regulated kinase (p-ERK), and phosphorylated cAMP response element-binding protein at serine 133 site (p-CREB-S133) were detected.

Results: The expressions of CGRP and CGRP1 receptor components were significantly upregulated in CM rats. CGRP1 receptor components were expressed mainly in neurons. BIBN4096BS treatment and PKC inhibition alleviated mechanical allodynia, thermal hyperalgesia and vestibular dysfunction in CM rats. Additionally, BIBN4096BS treatment and PKC inhibition markedly inhibited the overexpression of synaptic associated proteins and restored the abnormal synaptic structure in VN after CM. Furthermore, BIBN4096BS treatment dysregulated the expression levels of PKC, p-ERK and p-CREB-S133, and attenuated neuronal activation in VN after CM.

Conclusions: The present study demonstrated that CGRP1 receptor inhibition improved vestibular function after CM by reversing the aberrant synaptic transmission via downregulating PKC/ERK/CREB signaling pathway. Therapeutic interventions by inhibiting CGRP/CGRP1 signaling may be a new target for the treatment of vestibular symptoms in CM.