Migraines Flashcards
Describe the pathopysiology of migraines
Initiates in the hypothalamus
Activation of the trigeminal nerve in the brain stem
= Then activation of the trigeminal ganglion
= C-fibre activation = A-delta afferent activation
Unmyelinated C fibres from the trigeminal nerve surround the large cerebral vessels and dura mater of the meninges
C fibre activation = release of
Calcitonin gene-related peptide (CGRP)
Substance P
Neurokinin A
Substances produce blood vessel dilation, inflammation, stimulate Adelta fibres
5HT in migraines
5HT metabolites increase during a migraine attack (5HT levels decrease)
A 5HT infusion suppresses spontaneous and evoked migraines
5HT1b/1d > expressed in cranial arteries and trigeminal ganglia nerve terminals
5HT1f > present in trigeminal nerve terminals
5HT1b/1d expression
5HT1f expression
5HT1b/1d > cranial arteries and trigeminal nerve terminals
5HT1f > various trigeminal nerve terminals
What is CGRP (made up of)?
Where is it expressed
Calcitonin gene-related peptide
CGRP ligand = CRLR Receptor + RAMP1
Expressed in cranial arteries and trigeminal ganglia
List the possible migraine treatments
Triptans
Gepants
Ditans
Triptans; example, MOA, side effects
Sumatriptan, almotriptan, eletriptan
5HT1b/1d agonist > constricts cranial blood vessels > targets the trigeminal ganglia outside the BBB
Cannot pass the BBB
Also reduces CGRP levels
*contraindicated in cardiovascular disease (as causes coronary vasospasm
Side effects:
Dizziness, Drowsiness or fatigue, Flushing, Nausea
Ditans; example, MOA, side effects
Lasmiditan
5HT1f agonist (these receptors are found on trigeminal nerve terminals of C-fibres)
= no CVD issues reported
Side effects:
Headache, nausea, vomiting, dizziness,
Gepants MOA
Small molecule antagonists of CGRP receptor
Rimegepant (biohaven)
Reduces headache pain up to 24hrs
Reduces photophobia, nausea
Zavegepant; in clinical trials but can be administered intranasally
Ubrogepant
Erenumab MOA, benefit
First human IgG2 monoclonal antibody for migraines
Selectively targets and binds to CGRP receptor, blocking CGRP
Has a long duration of action = monthly injection
What’s different about a CGRP receptor?
Has 1 7 transmembrane domain protein + a single transmembrane domain protein; Receptor activity modifying protein (RAMO)
CGRP= CRLR receptor + RAMP 1
CGRP in migraines
Calcitonin gene-related peptide (CGRP) levels are increased during a migraine attack
Migraine patients infused with CGRP develop a delayed headache
CGRP released from nerves dilates arteries
CGRP receptors are expressed in cranial arteries and trigeminal ganglia
List characteristics of a migraine.
Severe unilateral pulsating pain
Throbbing headache
Associated with: Nausea, Vomiting, Sensitivity to sound and light
Can be accompanied by Auras; visual disturbances numbness, tingling
What is the trigeminal nerovascular system?
trigeminovascular system consists of bipolar neurons, with cell bodies within the trigeminal ganglion, and peripheral and central fibres connecting to cranial blood vessels and the spinal division of the trigeminal nucleus located in brainstem and upper cervical cord
What is the postdromal stage?
Can last up to a day after a migraine, symptoms can include;
Feeling tired, drained
Feeling unusually refreshed or happy
Muscle pain or weakness
Food cravings or lack of appetite
List the types of migraines
Common migraine - no aura
Classic migraine
Silent migraine - aura but no headache
Hemiplegic migraine - with weakness, loss of sensation on one side of the body
Retinal migraine - accompanied by temporary vision loss in one eye
