My own slim attempt at covering the extremely complex and ever evolving field of migraine pathophysiology. Not intended by any means to be exhaustive but more like a unique take and beginner's guide.

1. PATHOPHYSIOLOGY OF
MIGRAINE
DR MALLUM C.B

2. EXCITABLE BRAIN
• DRN- direct stimulation causes migraine.
Serotonin- central to forebrain. 5HT2- migraine.
5HT1 presynaptic- inhibits DRN, peripheral
stimulation from circulating serotonin.
Unstable serotonergic system.Ergot- 5HT1
stimulator. Ergotamine- vasodilator. Triptans-5HT1D
agonist.
• Descending analgesic pathway-
• PAG - Midbrain

3. PROF’S PATHOPHYSIOLOGY
• Prophylaxis – Inhibit 5HT2 in forebrain. eg
propranolol.
• Providing serotonin eg amitryptiline for
accumulation of serotonin at 5HT1.
• Tension headache – low level of serotonin.
• Moscowicz- AAN
• Goadsby.
• Genetic predisposition
• Menstrual- premenstrual migraine.

4. • Triggers that are repeatedly associated with an
Attack e g glare, loud noise, certain odors,
certain foods (or delaying a meal), hormonal
changes, head trauma, and NO.
premonitory symptoms irritable, have food
cravings, or experience fatigue or excessive
yawning.

5. CSD
• a migraine trigger
• CSD occurs in the cerebral cortex, cerebellum,
and hippocampus.
• Intracellular calcium rises
• NO, arachidonic acid, protons (H+), and
potassium (K+) are released extracellularly.
• Matrix metalloprotease affects the bloodbrain
barrier.
• Speed 3mm/s, goes to occipital,
• CSD causes aura.

6. CSD
• Meningeal nociceptors are activated.
• Mast cells are activated and degranulate.
• The trigeminovascular reflex is activated.
• Trigeminal neurons supplying the dural vessels
release calcitonin gene-related peptide (CGRP),
substance P, and neurokinin A.
• The vessels dilate and become inflamed, and
plasma protein extravasation occurs (also known
as sterile neurogenic inflammation).

7. peripheral sensitization
• At this point, the first-order trigeminal neuron
has been activated (peripheral sensitization)
and carries pain signals centrally.
• The patient may experience pounding pain
and pain with head movement.
• If treated during the early stages of an attack
when only peripheral sensitization has
occurred, the migraine may be terminated
fully.

8. trigeminoparasympathetic
reflex
• Through its polysynaptic connections with the
SSN(superior salivatory nucleus)
• parasympathetic fibers innervating the dural
vessels release acetylcholine, NO, and
vasoactive intestinal polypeptide.
• Clinically, the patient may develop miosis,
ptosis, a red eye, lacrimation, and nasal
stuffiness or rhinorrhea.

9. central sensitization
• second- and third-order neurons may be
activated (trigeminothalamic and
thalamocortical).
• the phenomenon known as wind-up is
involved.
• Glutamatergic and NO transmission are
involved.
• The clinical manifestation of
• central sensitization is cutaneous allodynia.

10. central sensitization
• The patient may report scalp tenderness and
facial, neck, or even extremity pain occurring
spontaneously or in response to nonpainful
stimuli.
• Patients may even report that their hair hurts.
• Once central sensitization has occurred, the
attack is much harder to treat, and triptan drugs,
such as sumatriptan, may no longer work.
• However, nonsteroidal anti-inflammatory drugs
• (NSAIDs) and dihydroergotamine may still be
effective.

11. central sensitization
• Central sensitization is more likely to occur as
the duration of an attack increases and is also
more likely to be present in chronic migraine
than episodic migraine.

12. Possible substrates for clinical features
of migraine
• Pain – trigeminovascular system
- throbbing: pain producing innervation of large
cranial vessels
- Unilateral: trigeminal nerve/nucleus.
• Nausea –Trigeminal connections with caudal
medial NTS
• Light- Abnormal brain stem modulation of
sensory input(locus coerulus)

13. ANATOMY OF MIGRAINE
Opthalmic division of the trigeminal nucleus –
cerebral vessels,pial vessels, large venous sinuses,
dura mater.
Upper cervical dorsal roots –posterior fossa
Neurons secrete substance P and CGRP
First order neuron- Trigeminal ganglion
Second order neuron- Trigeminal nucleus
(Quintothalamic tract) : Trigeminal nucleus caudalis
& and C1-2 dorsal horns.

14. PHYSIOLOGY OF PERIPHERAL
CONNECTIONS
• Plasma protein extravasation-
• Neuropeptide studies-CGRP & Substance P

15. PHYSIOLOGY OF CENTRAL
CONNECTIONS
• The Trigeminocervical complex-
From nucleus caudalis to dorsal horn of high
cervical cord.
These are second order neurons for intracranial
pain producing structures.
• Higher order processing- Thalamus: Ventral
posteromedial,medial nucleus of posterior
complex,intralaminar thalamus, Ventrobasal
complex

16. CENTRAL MODULATION
• Midbrain - Periaqueductal gray matter
• Hypothalamus -?
• Final - Cortex - Insulae , Frontal cortex ,
Anterior cingulate cortex ,Basal ganglia

17. RX
• Steroids as rescue medication in Chronic Daily
Headache.