Abstract
Cortical spreading depolarisation (CSD), the neural mechanism underlying migraine aura, may cause headache by sensitising the trigeminal system. Photophobia, the most bothersome accompanying symptom during migraine attacks, is more prevalent in migraine with aura than in migraine without aura. Whether CSD plays a role in developing photophobia remains unknown. Moreover, migraine-induced physical hypoactivity contributes to loss of productivity. We aimed to investigate the development of trigeminal sensitisation, photophobia and locomotive abnormality after KCl-induced CSD using 86 male C57BL/6 mice. Sham-operated mice were used as controls. We confirmed the presence of trigeminal sensitisation and photophobia at 24 h after CSD. CSD-subjected mice also exhibited significantly reduced locomotive activity in both light and dark zones. Hence, the CSD-induced hypomobility was likely to be independent of photophobia. The 5-HT1B/1D agonist, sumatriptan, corrected all these CSD-induced abnormalities. Moreover, dose dependency was demonstrated in the ameliorating effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, olcegepant, on these abnormalities. Sumatriptan and olcegepant improved mouse locomotion with therapeutic lags ranging from 20 to 30 min. Collectively, CSD caused trigeminal sensitisation, photophobia and hypomobility that persisted for at least 24 h by a mechanism involving the 5-HT1B/1D and CGRP activity.
Highlights
Cortical spreading depolarisation (CSD), the neural mechanism underlying migraine aura, may cause headache by sensitising the trigeminal system
The most convincing evidence in humans for the association between CSD and migraine aura came from observed alterations in blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) compatible with the visual percept experienced during an episode of visual aura 11
Vehicle-treated mice that underwent the CSD procedure were referred to as the CSD-Vehicle group. Those subjected to both CSD and pharmacological treatment were designated in accordance with the administered agent and dose: the CSD-Sumatriptan, CSDOlcegepant 0.25 and CSD-Olcegepant 1.0 groups
Summary
Cortical spreading depolarisation (CSD), the neural mechanism underlying migraine aura, may cause headache by sensitising the trigeminal system. The most convincing evidence in humans for the association between CSD and migraine aura came from observed alterations in blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) compatible with the visual percept experienced during an episode of visual aura 11. Based on these studies, CSD is speculated as the pathophysiological mechanism underlying migraine aura. In BOLD MRI studies and a sound-induced visual illusion test, MA patients showed greater excitability of the occipital cortex to visual stimuli compared with MO p atients[19,21,22] These findings raise the following two possibilities. Locomotive activity serves as an index to evaluate functionality of migraine patients
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