Migraine

Question 1

what is the International Headache Society definition:

Answer 1

(1) a headache that lasts for 4-72 hours
(2) at least two of:
- unilateral localization
- pulsating quality
- moderate to severe pain intensity
- aggravation by movement
(3) at least one of:
- nausea and/or vomiting
- photophobia and phonophobia

Question 2

what are the Four main phases of the migraine:

Answer 2

Four main phases of the migraine:
(i) premonitory, (ii) aura (e.g. visual), (iii) headache, and (iv) postdrome

Question 3

what is the Pathophysiology of migraine

Answer 3

Theories have evolved from purely vascular to purely neurological
- Current thinking is that both are involved -> neurovascular
- Activation of trigeminovascular pathways -> meningeal vasodilation,
neurogenic inflammation, central sensitization, perceived head pain
Huff and Daly 2020. PMID: 29489263
Henry Gray – 1918 Gray’s Anatomy Plates

Question 4

what is the target of the migraine medications

Answer 4

Agents that target the serotonin 5-HT 1 receptors

Question 5

give two examples of the ergot alkaloids medications

Answer 5

ergotamine (no longer used in Canada)
(ii) dihydroergotamine
- nasal spray and injection (IV, SC, IM)
- high dose and drug interactions can cause adverse effects

Question 6

how does First generation migraine medications work

Answer 6

ergot alkaloids
- act as an agonists at 5-HT 1B and 5-HT 1D receptors
- reduce trigeminal neuron activation, inducing vasoconstriction
of meningeal blood vessels
- are also agonists at additional 5-HT receptors and D1/D 2 receptors,
and likely other receptors

Question 7

what is the Second generation anti migraine

Answer 7

Second generation: triptans

Question 8

which receptor does triptans target

Answer 8

act as an agonists at 5-HT 1B and 5-HT 1D receptors

Question 9

what is the effects of triptans on the Periphery

Answer 9

Periphery
(i) activation of 5-HT 1B receptors induces vasoconstriction
(ii) activation of 5-HT 1D receptors blocks the release of vasoactive
peptides that trigger neurogenic inflammation

Question 10

what is the effects of triptans on the Central

Answer 10

Central
(iii) interference with afferent nociceptive signalling to the
trigeminocervical complex

Question 11

what are the NSAIDS

Answer 11

NSAIDS
- non-specific agents: ibuprofen, diclofenac, and naproxen
- analgesic, antipyretic, anti-inflammatory
- inhibit cyclooxygenase (COX) 1- and 2-mediated synthesis of prostanoids
from arachidonic acid

Question 12

where are the Calcitonin gene-related peptide (CGRP) located

Answer 12

Calcitonin gene-related peptide (CGRP)
- found in the sensory fibers from the dorsal root and trigeminal ganglia
- the CGRP receptor activates the Ga s G protein-coupled receptor

Question 13

what is the erenumab injection

Answer 13

• for the prevention of migraine
• launched December of 2018
• humanized monoclonal antibody
  against CGRP receptor
• administered monthly by the
  patient via AUTO injection
• subcutaneous administration

Question 14

what is the pathophysiology of Calcitonin gene-related peptide (CGRP)

Answer 14

Calcitonin gene-related peptide (CGRP)
- likely involved in migraine pathophysiology
(i) CGRP levels increased in serum and saliva during migraines
(ii) triptans lower CGRP levels
(iii) injection of CGRP induces headache in migraineurs
(iv) CGRP receptor antagonists relieve pain and other symptoms