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Pathophys of migraines
Lecture 15
18
Pharmacology
Professional
09/12/2012

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Term
What are 4 changes that occur in patients with migraine?
Definition
- Genetics - 50% genetic. Chromosome 19, more women than men. Increases in calcium, increase in glutamate, reduced reuptake of glutamate, increased sodium.
- Peripheral sensitization - lower stimulation
- Central sensitization - TNC releases glutamate and CGRP to result in central sensitization. PAG, LC, and NRM lose inhibitory effects.
- Allodynia
Term
What is the prodromal phase?
Definition
preheadache phase occuring 24-72 hours before attack in 30-70% of sufferers.
- A release of dopamine in hypothalamus leads to depression, yawning, decr appetite, irritability, STIFF NECK
Term
What is the Aura stage in migraines?
Definition
seen in 20-25% of patients, shortly before the attack, VISUAL changes, motor and speech deficits. Neuronal depolarization seen as cortical spreading depression (CSD) --> high ECF potassium, excess glutamate, low magnesium.
Term
Where does the cortical spreading depression begin, and what is it?
Definition
In the occipital lobe -- hyperactivity initiates dilation using NO followed by constriction. Initially dilation causes the attack
Term
What is a scotoma?
Definition
Area of diminished vision (blind spot). Loss or addition to structures
Seen in an aura.
Term
What are the major features of a migraine attack?
Definition
Repeated episodic headache located in the sinuses, temples/eyes, and occipital region
Any two: Unilateral pain, throbbing, worsened by movement, moderate to severe
Any one: N/V, photophobia, phonophobia
Term
Which major artery is involved in migraines and also supplies blood to the dura mater?
Definition
Middle meningeal artery - a branch of the external carotid.
Behind the maxillary artery.
Term
What structures are involved in a migraine?
Definition
Internal and external cranial arterial BVs: External carotid, superficial, maxillary, and occipital artery.
Meninges
Nerves - trigeminal nerve
Term
Which arteries branch off the internal carotid?
Definition
Subclavian --> Common carotid --> Internal and external --> Internal carotid branches into vertebral artery and basilar artery. Opththamalic artery.
Term
What are the three meninges that protect the brain?
Definition
- Dura mater - outermost, supplied blood by middle meningeal artery
- Arachnoid mater - above the subarachnoid space
- Pia mater - covers surface of the brain
Term
Are there pain receptors in the brain?
Definition
No! Pain due to restriction of blood in the dura and pia mater, which is ennervated by the TGV system: Opthamalic (1) nerve and trigeminal (5) nerve
- Trigeminal nerve is sensory/motor and has 3 branches: Ophthalamic (1), Maxillary (2), and Mandibular (3)
Term
How does the TGV afferent system work?
Definition
A signal travels from a BV up trigeminal ganglia to the TNC (1st order) --> 2nd order neuron to the thalamus --> 3rd order to the somatosensory cortex and release of Ach. The PAG, LC, and RM normally filter impulses using serotonin. CGRP and NO released from blood vessels in response to signal --> dilation
Term
How do we known serotonin is low in migraine headaches?
Definition
The PAG, LC, and RM normally filter impulses using serotonin. If serotonin is not present, no filtering or modulation occurs.
Term
What are the two major theories of migraine headaches?
Definition
- Vasogenic - pain comes from extracranial vasculature. Constriction is the stimulus (aura) then vasodilation -- Vasoconstriction does not explain aura
- Neurogenic - pain comes from sensory nerves than innervate BVs of meninges. Mediators lead to vascular changes -- release of NO acting on the middle meningeal artery
Term
What is a brain freeze?
Definition
Sudden increase in blood flow, constriction to reduce this blood flow
Term
How does cortical spreading depression explain a migraine?
Definition
- Neurons prone to excitability
- Neurons release NO --> trigeminal nerve --> pain signals
- NO and CGRP--> dilation --> inflammation and pain from histamine, increase in vascular permeability
Term
How does the CSD release CGRP?
What are other genetic mutations that trigger migraine?
Definition
A major mediator, depolarization waves release CGRP, cause the AURA!
- increase in calcium on trigeminal nerves --> increase in glutamate and CGRP, decrease in Mg (prevents influx of Na/Ca)
- Loss of Na/K ATPase function - decreased reuptake of glutamate
- reduced firing of GABA neurons
- Increased sodium levels
Term
What effect does low magnesium have?
Definition
Exaggerated glutamate response, binds to sodium channels, sodium depolarizes nerve
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