How is migraine caused?

The exact cause and pathogenesis of migraine are still under discussion. Many factors can induce, aggravate or relieve migraine attacks. Scholars have also put forward some theories through physical or chemical methods.

For some individuals, many changes in the external or internal environment can stimulate or aggravate the migraine attack.

1. Hormone changes Oral contraceptives will increase the frequency of migraine attacks; Menstruation is a common trigger or aggravating factor of migraine ("periodic headache"); Pregnancy and sexual intercourse can cause migraines ("sexual headaches").

2. Some drugs Some susceptible individuals may have typical migraine attacks after taking nifedipine, isosorbide nitrate or nitroglycerin.

The weather is changeable, especially when it becomes hot, cloudy or humid.

4. Some food additives and drinks are the most common alcoholic drinks, such as some red wine; Dairy products, cheese, especially hard cheese; Coffee; Foods containing nitrite, such as soup and hot dogs; Some fruits, such as citrus fruits; Chocolate ("chocolate headache"); Certain vegetables; Yeast; Artificial candy; Fermented pickled products such as pickles; Monosodium glutamate.

5. Slight movement of moving head can induce or aggravate migraine attack, and some patients are afraid to take the bus for fear of causing migraine attack; Football players can induce headaches by heading the ball ("footballer's migraine"); Going upstairs and climbing stairs can cause migraine.

6. Too much or too little sleep.

7. Miss or postpone the meal.

8. Smoking or exposure to smoke.

9. Flash, the light is too strong.

10. Nervousness, anger, depression, crying ("crying headache"), many women go shopping or go to crowded places to cause migraine attacks; Some people ride horses abroad, although the crowd is less than 1min, but it can also aggravate migraine.

Among the stimulating factors, quantity, interaction and individual differences should be considered. For sensitive individuals, eating an orange may not cause headaches, while eating a few oranges may cause headaches. In some cases, eating a few oranges won't cause headaches, but if there are menstrual effects at the same time, this combined effect will cause migraine attacks. Some individuals will have migraine attacks if they stay in the mall for a while, and some individuals will have migraine attacks if they stay in the mall for a long time.

There are many factors to improve migraine. When migraine attacks, lying down for a while can relieve headaches. Someone closed his eyes in a dimly lit room to relieve his headache. Some people like to press their temples with their hands when they have a headache to relieve the headache, while others use cold water to wash their hair to relieve the headache. Migraine often relieves in postmenopausal women and after 3 months of pregnancy.

(2) Pathogenesis

Several theories about pathogenesis;

1. The theory of vasoactive substance 5- hydroxytryptamine is the most mentioned theory by scholars. It was found that the concentration of 5-HT in platelets decreased during migraine attack, while the 5-HT metabolite 5-HT hydroxyindoleacetic acid in urine increased.

5-HT neurons and noradrenergic neurons in the brain stem can regulate the relaxation and contraction of intracranial blood vessels. Many 5-HT receptor antagonists are effective in treating migraine. Depletion of 5-HT with reserpine can accelerate the occurrence of migraine.

2. Neurovascular meningeal response of trigeminal nerve stimulates trigeminal nerve in rodents, which can cause meningeal inflammation, and ergotamine, dihydroergotamine, sumatriptan and other drugs for migraine can prevent this neurogenic inflammation.

Calcitonin gene-related peptide (CGRP) released by trigeminal nerve can be detected in migraine patients, and CGRP is a strong vasodilator. Dihydroergotamine and sumatriptan can not only relieve headache, but also reduce the content of calcitonin gene-related peptide. So the pain of migraine is aseptic meningitis caused by neurovascular inflammation. Wilkinson believes that trigeminal nerve is distributed in pain-related areas, and migraine may be a neurogenic inflammation. Solomon pointed out that the diplopia of migraine with ophthalmoplegia in children originated from the swelling of internal carotid artery in cavernous sinus and the third damage to brain nerve after reviewing the research literature of migraine in children. Another explanation is that the swelling of the superior cerebellar artery and the posterior cerebral artery causes the third injury to the brain, which may also be inflammation of the nerve.

3. There are a large number of endogenous opioid peptides related to analgesia, such as enkephalin and β-endorphin, in periaqueductal gray matter and the fourth ventricle floor of midbrain with endogenous pain control system disorder. Under normal circumstances, these substances play an analgesic role by regulating afferent pain. Although the reported results are different, most reports show that β -endorphin or its analogues in cerebrospinal fluid or plasma of migraine patients decrease, suggesting that migraine patients have endogenous pain control system disorder. This disorder leads to the decrease of pain threshold, the enhancement of pain sensitivity and the easy occurrence of pain. Salmon calcitonin can improve the plasma β -endorphin level while treating migraine.

4. The autonomic nervous dysfunction has been concerned by scholars for a long time. The study of instantaneous heart rate variability and cardiovascular reflex shows that the sympathetic nerve function of migraine patients is low. The study of 24-hour dynamic heart rate variability shows that migraine patients have sympathetic and parasympathetic nerve dysfunction. Some scholars have also reported that the pupil diameter of migraine patients is uneven, suggesting that these patients have abnormal autonomic nervous function. Some people think that sudden death of migraine patients may be related to autonomic nerve dysfunction.

5. Family aggregation and genetic research. Migraine patients have a certain tendency of family aggregation. Genetic factors are the most obvious, and familial hemiplegic migraine and basal migraine are also studied more. Migraine with aura has higher family aggregation than migraine without aura. Threatened migraine and hemiplegia can appear alternately in the same individual and the same family at the same time. Based on this, scholars believe that familial hemiplegic migraine and uncomplicated migraine may have the same pathophysiology and etiology. Baloh et al. reported several families, many of whom have migraine, dizziness or primary nystagmus, some have progressive peripheral vestibular dysfunction in their later years, and some family members tend to have the same onset age, such as symptoms before the age of 25.

It has been reported that the genetic defect of hemiplegic migraine families is related to chromosome 19, but some studies have found that some hemiplegic migraine families are not related to chromosome 19, suggesting that there is genetic variation in familial hemiplegic migraine. The frequency of paroxysmal disturbance of consciousness in migraine patients with familial hemiplegia associated with chromosome 19 is high, suggesting that the lower external trigger threshold of migraine associated with chromosome 19 is determined by genes. Ophoff reported 34 families with familial hemiplegic migraine related to chromosome 19. There are four different crossover mutations in the functional region encoded by voltage-gated calcium channel α 1 subunit gene.

There is a familial paroxysmal ataxia with intermittent nystagmus, which is manifested as ataxia. Vertigo with intermittent nystagmus is a dominant hereditary neurological dysfunction. About 50% of these patients suffer from migraine without aura, and their clinical symptoms overlap with familial hemiplegic migraine. Both of them are related to the typical state of basal migraine, and both of them can have primary nystagmus and progressive ataxia. Ophoff reported two cases of familial ataxia with paroxysmal nystagmus, and there was a voltage-dependent calcium channel gene mutation on chromosome 19, which was the same as that detected in familial hemiplegic migraine. The difference is that its reading frame is interrupted, resulting in a truncated α 1 subunit, which leads to the decrease of calcium channel density which can be expressed in cerebellum in a large amount under normal circumstances, which may explain its paroxysmal and progressive ataxia. In familial hemiplegic migraine, it is still unknown how the same crossover mutation leads to hemiplegia.

Baloh reported 3 cases of familial migraine with bilateral vestibular lesions. Many members of the family experienced migraine, dizziness (for a few minutes) and vestibular dysfunction in their later years. The cessation of vertigo attack, balance disorder and walking swing in the later stage are caused by the loss of bilateral vestibular function. The author thinks that the calcium channel subunit mutation may be selectively expressed on vestibular hair cells, which explains paroxysmal vertigo and progressive bilateral vestibular lesions when hearing is normal.

6. Vasospasm theory Extracranial vasodilation can be accompanied by a typical migraine attack. Whether migraine patients have intracranial vasospasm is still controversial. It used to be thought that the visual aura of migraine was caused by vasospasm. Now there is definite evidence that this halo is caused by the inhibition of neuronal activity (3mm/min) from occipital cortex to frontal cortex. Vasospasm is more like the initial cause of retinal migraine. Some patients have short-term monocular blindness, and retinal artery spasm can be found during the attack. In addition, these patients responded to vasospasm drugs. Hearing loss and/or vertigo associated with migraine can be explained based on vasospasm of cochlea and/or vestibular branch of internal auditory artery. Vasospasm can lead to ischemic injury of internal lymphatic vessels or cysts, damage of lymphatic circulation, and finally develop into edema. Transcranial Doppler (TCD) measurement of cerebral blood flow velocity found that the blood flow velocity increased during or between migraine attacks, suggesting that intracranial vascular tension in these patients increased.

7. Many clinical features of ion channel disorder migraine syndrome are related to hereditary ion channel disorder. There is local extracellular potassium accumulation in the inner ear of migraine patients. When calcium enters neurons, potassium leaves. Because ion channels in the inner ear are very important to maintain the excitation function of potassium-rich endolymph and neurons, the defects of ion channels in the brain and inner ear can lead to reversible hair cell depolarization and auditory and vestibular symptoms. Headache in migraine is a secondary phenomenon, which is the result of the increase of extracellular potassium concentration. Many inducing factors of migraine syndrome, including tension and menstruation, may be the result of hormone affecting defective calcium channels.

8. Other theories have found that migraine has spontaneous platelet aggregation and increased viscosity during the attack. It has also been found that migraine patients have the imbalance of TXA2 and PGLI2, and the changes of substance P and neurokinin.