Cortical Spreading Depression Closes Paravascular Space and Impairs Glymphatic Flow: Implications for Migraine Headache

During the past few decades, much controversy has surrounded the pathophysiology of migraine. Cortical spreading depression (CSD) is widely accepted as the neuronal process underlying visual auras. It has been proposed that CSD can also cause the headaches, at least in migraine with aura. We describe three patients, each fulfilling the International Headache Society criteria for migraine with aura, who suffered from headaches 6–10 days per month. Two patients were treated with flunarizine and the third patient with topiramate for the duration of 4 months. All patients reported that aura symptoms resolved completely, whereas the migraine headache attacks persisted or even increased. These observations question the theory that CSD (silent or not) is a prerequisite for migraine headaches.

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Pathophysiology of migraine: From molecular to personalized medicine

Medicinski pregled ◽

10.2298/mpns1302053k ◽

2013 ◽

Vol 66 (1-2) ◽

pp. 53-57 ◽

Cited By ~ 9

Author(s):

Zvezdana Kojic ◽

Dobrica Stojanovic

Keyword(s):

Personalized Medicine ◽

Cortical Spreading Depression ◽

Migraine Headache ◽

Spreading Depression ◽

Occipital Lobe ◽

Peripheral Sensitization ◽

Cutaneous Allodynia ◽

Migraine Pathophysiology ◽

Hereditary Nature ◽

The Brain

Introduction. Understanding of migraine pathophysiology has substantially improved over the last two decades. As a result, migraine is now mainly considered to be a disorder of the brain, rather than one of the vasculature or the meninges. Pathophysiology. Although it remains speculative how exactly they relate to each other, the following three processes are important in migraine: 1. Cortical spreading depression is a wave of intense depolarization, it starts in the occipital lobe, propagates through the brain and is followed by a period of suppressed activity. 2. Activation of the trigemonovascular system causes the release of neuropeptides (e.g. calcitonin gene-related peptide, substance P) from the peripheral trigeminal nerve endings. These neuropeptides are thouglt to play a role in causing and maintaing headache. 3. Sensitization of peripheral and central brain areas, it is thought that pulsating quality of migraine headache is caused by a process of peripheral sensitization. Cutaneous allodynia is a marker of central sensitization. Link between Aura and Headache. The view that the aura is caused by cortical spreading depression has become generally accepted, and the same is true for the view that activation of the trigemonovascular system underlies migraine headache. However, the relationship between the aura and the activation of the trigemonovascular system and the start of headache remains elusive. Genetics of Migraine. One of the most important aspects of the pathophysiology of migraine is the hereditary nature of the disorder. Conclusion. Identification of polymorphisms and genetic biomarkers should help us to understand migraine pathophysiology better and thus enable the development of specific, effective ?individually-tailored treatment? for each particular migraine patient (personalized medicine).

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A potential role for two brainstem nuclei in craniovascular nociception and the triggering of migraine headache

Cephalalgia ◽

10.1177/0333102420960039 ◽

2020 ◽

pp. 033310242096003

Author(s):

Alessandro S Zagami ◽

Sumaiya Shaikh ◽

David Mahns ◽

Geoffrey A Lambert

Keyword(s):

Dura Mater ◽

Cortical Spreading Depression ◽

Migraine Headache ◽

Spreading Depression ◽

Light Flash ◽

Discharge Rate ◽

Indirect Evidence ◽

Second Order ◽

Facial Skin ◽

Migraine Triggers

Aim To use an animal model of migraine to test whether migraine headache might arise from a brainstem-trigeminal nucleus pathway. Methods We measured evoked and spontaneous activity of second-order trigeminovascular neurons in rats to test whether the activity of these neurons increased following the induction of cortical spreading depression or the imposition of light flash – two potential migraine triggers, or headache provokers. We then tested whether drugs that could activate, or inactivate, neurons of the nucleus raphe magnus or the periaqueductal gray matter, would affect any such increases selectively for the dura mater. Results Injection of sodium glutamate (a neuronal excitant) into these two nuclei selectively inhibited the responses of trigeminovascular second-order neurons to dura mater, but not to facial skin, stimulation. Injection of lignocaine (a local anaesthetic) into these nuclei selectively potentiated the responses of these neurons to dura, but not to facial skin, stimulation. Furthermore, injections into either nucleus of glutamate inhibited the increase in the ongoing discharge rate of these neurons produced by cortical spreading depression and light flash. Conclusions These results provide indirect evidence that trigeminovascular nociception may be tightly controlled by these two nuclei, whereas cutaneous trigeminal sensation may be less so. These nuclei may be relays of one possible brainstem-trigeminal pathway that could mediate migraine headache. Modification of neuronal activity in these two nuclei produced by migraine (headache) triggers may lie behind the pain of a migraine attack, at least in some cases.

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