Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Neurology, Danish Headache Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark; Translational Research Centre, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Trends Neurosci. 2024 Nov;47(11):918-932. doi: 10.1016/j.tins.2024.08.012. Epub 2024 Sep 19.
Migraine is a highly prevalent and disabling pain disorder that affects >1 billion people worldwide. One central hypothesis points to the cranial meninges as a key site underlying migraine headache genesis through complex interplay between meningeal sensory nerves, blood vessels, and adjacent immune cells. How these interactions might generate migraine headaches remains incompletely understood and a subject of much debate. In this review we discuss clinical and preclinical evidence supporting the concept that meningeal sterile inflammation, involving neurovascular and neuroimmune interactions, underlies migraine headache genesis. We examine downstream signaling pathways implicated in the development of migraine pain in response to exogenous events such as infusing migraine-triggering chemical substances. We further discuss cortex-to-meninges signaling pathways that could underlie migraine pain in response to endogenous events, such as cortical spreading depolarization (CSD), and explore future directions for the field.
偏头痛是一种普遍存在且使人丧失能力的疼痛障碍，影响着全球超过 10 亿人。一个中心假说指出，颅脑膜作为偏头痛头痛发生的关键部位，通过脑膜感觉神经、血管和相邻免疫细胞之间的复杂相互作用。这些相互作用如何产生偏头痛头痛仍不完全清楚，这也是一个争论的话题。在这篇综述中，我们讨论了支持脑膜无菌性炎症的概念的临床和临床前证据，该炎症涉及神经血管和神经免疫相互作用，是偏头痛头痛发生的基础。我们研究了下游信号通路，这些通路涉及对外部事件（如输注偏头痛触发化学物质）的反应，从而导致偏头痛疼痛的发展。我们进一步讨论了皮质到脑膜信号通路，该通路可能是对皮质扩散性去极化（CSD）等内源性事件引起的偏头痛疼痛的基础，并探讨了该领域的未来方向。
