Lecture 64 Serotonin and Migrane
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How much of the population is affected by migranes?
How many people who have migranes have ever consulted their doctor about their migrane?
Is a migrane a leading disabling medical illness according to WHO?
What is the ratio of children males to females who suffer from migranes?
How long can a migrane last?
What are the requirements for a migrane headache?
- Two of the following: unilateral pain, throbbing, aggrevation on movement, pain of moderate/severe intensity
- One of the following: nausea/vomiting, photophobia/phonophobia
What are the four things that must be assessed to make a migrane diagnosis?
- Medical Hx
- Headache Diary
- Migrane Triggers
- Exclusion of secondary causes: EEG, MRI, CT
What are the phases of an acute migrane headache?
When does a prodrome happen relative to the headache in a migrane?
12-36 hours before. but only last 15-20 minutes
What are the symptoms of the prodrome stage of a migrane headache?
- craving/distaste for certain foods
What is an aura?
- a warning or signal immediately before the onset of a headache that does not alway occur in migranes
- duration=15-30 minutes
What are the symptoms of an aura?
- flashing lights
- zig-zag lines
- difficulty focusing
What are the accompanying symptoms of a migrane headache?
How long can the postdrome phase of a migrane last?
few hours- 2 days
What are the symptoms of a postdrome phase of a migrane headache?
- severe exhaustion/feeling fresh
What is a common migrane?
Migrane without aura
What is a classic migrane?
Migrane with aura
What is the diagnosis of a complicated migrane?
includes migrane + other symptoms, such as tremor
What classification does serotonin/5-hydroxytryptamine fit into?
Where is serotonin located?
- in the GI enterochromaffin cells(90%)
- on platelets
- in the brain
How is serotinin synthesized?
- from tryptophan consumed in the diet
- it takes two step to make serotonin from tryptophan
Why is measuring serotonin in the blood not a good method for determining the brain's supply of serotonin?
B/c not distributed equally~very large amounts in the GI tract
How many different types of serotonin receptors exist in the body?
at least 15
What kind of receptors are serotonin receptors?
G-protein receptors with one exception: 5-HT3, which is ligand gated
What does the serotonin receptor 5-HT1A play a role in?
What does the receptor 5-HT1D play a role in?
What does the receptor 5-HT3 play a role in?
What are the two types of autoreceptors found in serotonigeric neurons?
- somatodendritic autoreceptors: 5-HT1A
- Pre-synaptic autoreceptors: 5-HT1D
What are the pharmacological/physiological effects of serotonin?
- GI tract/small intestine
- vomiting b/c of vagal afferents chemo-receptor trigger zone
- platelet aggregation
- Bezold Jarrisch Reflex
What is the Bezold Jarrisch Reflex?
stimulation of sensory nerve endings by serotonin in baroreceptors and vagal afferents in coronary circulation leading to bradycardia and hypotension
What kind of tumor presents with diarrhea, bronchoconstriction, and edema due to large amounts of serotonin release?
What are the roles of serotonin in the CNS?
- pain perception
- behaviors (disorders include: depression, schizophrenia, OCB
- neuroendocrine regulation
Where does the pain from migrane headaches come from?
- the vasodialation of vasculature
- remember brain parynchema is insence
Are migranes a vascular disorder or a CNS disorder?
What is the pathophysiology of a migrane headache?
neural events trigger symptoms and produce dialation of blood vessels, which, in turn causes pain and further neuronal activation
All genes that have been connected to migrane headaches encode for what?
- neuronal proteins
- this is why it is a CNS disorder!
What does the gene CACNL1A4 code for and what kind of mutation does it need to produce hemiplegic migranes?
- alpha1 subunit of brain specific P/Q-type Ca++ channels
- gain of function mutations would cause a hemiplegic migrane
What does the ATP1A2 gene code for and what kind of mutation of this gene would result in a hemiplegic migrane?
- alpha2 subunit Na+/K+ pump in astrocytes
- loss of function of this gene would cause hemiplegic migranes
What does the gene SCN1A code for?
neuronal voltage gated Na+ alpha subunit
What are tryptans used to treat?
What are the mechanisms of tryptans?
- cranial vasoconstriction
- peripheral neuronal inhibition
- inhibit transmission via neurons of the trigeminocervical complex
What effect do triptans have on CGRP?
they are antagonists and prevent CGRP from being released
What are some adverse effects of triptans?
- sensations of warmth
- neck pain/stiffness
- chest pains due to coranary artery constriction
Are triptans really that effective at relieving migranes?
No; recall study where only two drugs showed any improvement at all
What are four non-specific treatments for migranes?
What are the requirements for prophylaxis for migrane sufferers?
- >2 headaches a month
- duration>48 hours
- severity is extreme
- prolonged auras
- do not respond to normal therapy
- risk of permanent neurological injury
What is the gold standard for prophylaxis medication for migranes?
What is the starting dose for propanolol?
What is the maximum dose for propanolol?
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