Department of Neurology, Tokai University School of Medicine, Isehara 259-1193, Japan.
Department of Human and Information Science, Tokai University, Hiratsuka 259-1292, Japan.
Int J Mol Sci. 2024 Jul 22;25(14):7980. doi: 10.3390/ijms25147980.
Migraine is a complex disorder characterized by episodes of moderate-to-severe, often unilateral headaches and generally accompanied by nausea, vomiting, and increased sensitivity to light (photophobia), sound (phonophobia), and smell (hyperosmia). Photophobia is considered the most bothersome symptom of migraine attacks. Although the underlying mechanism remains unclear, the intrinsically photosensitive retinal ganglion cells (ipRGCs) are considered to be involved in photophobia associated with migraine. In this study, we investigated the association between the sensitivity of ipRGCs and migraines and cortical spreading depression (CSD), which may trigger migraine attacks. The pupillary responses closely associated with the function of ipRGCs in patients with migraine who were irradiated with lights were evaluated. Blue (486 nm) light irradiation elicited a response from ipRGCs; however, red light (560 nm) had no such effect. Melanopsin, a photosensitive protein, phototransduces in ipRGCs following blue light stimulation. Hypersensitivity of ipRGCs was observed in patients with migraine. CSD was more easily induced with blue light than with incandescent light using a mouse CSD model. Moreover, CSD was suppressed, even in the presence of blue light, after injecting opsinamide, a melanopsin inhibitor. The hypersensitivity of ipRGCs in patients with migraine may induce CSD, resulting in migraine attacks.
偏头痛是一种复杂的疾病，其特征是发作性中度至重度、常为单侧头痛，通常伴有恶心、呕吐和对光（畏光）、声音（恐声症）和气味（超敏反应）的敏感性增加。畏光是偏头痛发作最恼人的症状。尽管其潜在机制尚不清楚，但内在感光视网膜神经节细胞（ipRGC）被认为与偏头痛相关的畏光有关。在这项研究中，我们研究了 ipRGCs 的敏感性与偏头痛和皮质扩散性抑制（CSD）之间的关联，CSD 可能引发偏头痛发作。评估了偏头痛患者在接受光照刺激时与 ipRGC 功能密切相关的瞳孔反应。蓝光（486nm）照射会引起 ipRGCs 的反应；然而，红光（560nm）则没有这种效果。视蛋白是一种感光蛋白，在蓝光刺激下在 ipRGCs 中进行光转导。偏头痛患者的 ipRGCs 敏感性增加。使用小鼠 CSD 模型，与白炽灯相比，蓝光更容易诱导 CSD。此外，即使在注射视蛋白抑制剂 opsinamide 后，CSD 也会被抑制，即使在蓝光存在的情况下也是如此。偏头痛患者 ipRGCs 的高敏感性可能会诱导 CSD，从而导致偏头痛发作。
