Lecture 40: The pathophysiology of migraine and other headaches

Question 1

What are the two types of headaches?

Answer 1

Primary headaches: a disorder unto itself like migraine

Secondary: a symptom of another disorder

Question 2

What is migraine?

Answer 2

Headache +
-unilateral, pulsating quality
-photo/phonophobia
-nausea or vomiting
-aggravated by movement
Can also have aura

Question 3

What is aura?

Answer 3

A fully reversible visual, sensory or speech disturbance
Example: seeing kaleidoscopes
Lasts between 5-60 mins

Question 4

If a patient presents with aura (seeing kaleidoscopes), what type of headache should you think about?

Answer 4

Migraine (second phase of migraine)

Question 5

What is a tension-type headache?

Answer 5

Tightening quality (like something is clamping
Non-pulsatile
-not aggravated by movement

Question 6

Aside from tension headaches and migraines, what do other primary headaches present with?

Answer 6

Autonomic features (watery eye, droopy eyelid, runny nose)
Side-locked features
Examples: Cluster headache, paroxysmal hemicranias

Question 7

What are chronic headaches?

Answer 7

The chronic form of primary headaches

-associated with a high frequency for at least several months

Question 8

What causes pain at the back of your head?

Answer 8

C2 cervical root via the occipital nerve

Question 9

What is the epidemiology of headache?

Answer 9

Episodic tension-type headache = 40%

Migrains = 18% in women and 6% in men

Question 10

What are the areas of the head that are sensitive to pain?

Answer 10

1. Face (trigeminal and C2)
2. scalp
3. Dura
4. Arteries
5. Venous sinus
   Opthalmic branch is responsible for pain sensation in these structures

Question 11

Why do patients often report pain in forehead/behind their eyes?

Answer 11

Because ophthalmic branch of trigeminal nerve innervates pain sensation for all the intracranial structures…this is a referred pain

Question 12

What is the pathway for painful messages coming from the head?

Answer 12

Afferents in trigeminal ganglion  spinal trigeminal tract  nucleus caudalis of spinal trigeminal  VPM  S1

Question 13

Why do patients with migraine feel pain in back of head?

Answer 13

Because the spinal trigem nucleus receives input from the occipital area innervated by C2

Question 14

How do you explain the symptoms besides pain that comes with migraine?

Answer 14

Spinal trigeminal nucleus makes connections with other nuclei in brainstem, thalamus, hypothalamus
Example: nuclei in brainstem can send reciprocal signals back down to modify pain
Connected to the superior salivatory nucleus (parasympathetic)
Connected to hypothalamus that leads to appetite changes
Connected to posterior nucleus of thalamus that leads to vision, hearing, memory, motor deficits

Question 15

What is the trigeminocervical complex (TCC)?

Answer 15

The area where afferent CNV neruons that innervate meninges terminate
Comprises C1-C2 dorsal horns of cervical spinal cord as well
So nucleus caudalis + C1,2

Question 16

What is Vascular theory of headache?

Answer 16

Blood vessels have been theorized to be sensitive to pain
VasoCONSTRICTION  decreased blood flow  compensatory vasodilation in blood vessles  inflammation  headache
Evidence supporting is that vasodilators can trigger migraine
Evidence against: functional imaging shows headache does not start until normalization of blood flow (so not due to initial reaction to vasoconstriction)

Question 17

What is the pathophysiology of migraine (neurovascular theory)?

Answer 17

1. Abnormal cortical activity
2. Cortical Spreading Depression
3. Activation/Sensitization of Trigeminovascular System
   4a. Abnormal brainstem activity
   4b. Central Sensitization
4. Pain and other symptoms

Question 18

What initiates migraine? Genetic component?

Answer 18

Abnormal cortical activity
Brains that are hyperexcitable by shit like alcohol or disrupted sleep are more likely to have migraine
Is heritable; relatives of migraineurs have 3x risk of having migraine
Example of gene: CACNA1A leads to Familial Hemiplegic Migraine

Question 19

What is Familial Hemiplegic Migraine?

Answer 19

Symptoms: Headache, aura, MOTOR WEAKNESS
-associated with 3 genes (CACNA1A, ATP1A2 and SCN1A)
Example of heritable migraine

Question 20

What leads to hyperexcitability?

Answer 20

1. hormones (like menstruation
2. stress, diet, sleep change, sensory stimuli
   Leads to abnormal cortical activity

Question 21

What is cortical spreading depression?

Answer 21

One step of the pathway that leads from hyperexcitability of brain to migraine symptoms (rest of shit unknown)
-phenomenon in which the ELECTRICAL ACTIVITY spreads from occipital lobe rostrally during headache
Mechanism unclear but could have to do with inappropriate release of glutamate

Question 22

So what is the theoretical connection between CSD and trigeminal activation?

Answer 22

CSD triggers release of chemicals that sensitize meningeal nociceptors. When they are sensitized, they perceive non-painful stimuli as painful (allodynia)
Example: normal pulsations of blood vessels then become painful and walking up stairs makes it worse
Possible molecular mechanism in more detail:
1. K+, H+ efflux leads to inflammation of blood vessels
2. perivascular axons release neruopeptides in response that leads to histamine, serotonin and bradykinin release from mast cells
3. this then sensitizes meningeal nociceptors which send shit to trigeminal ganglion

Question 23

Where does the pain come from?

Answer 23

The activation and sensitization of the trigeminovascular system
-involves transmission of signals from the trigeminal nerve and nucleus

Question 24

What is responsible for central sensitization?

Answer 24

Aberrant sensitization of the second order neuron

Consequence: messages of normal touch from A-beta fibers become painful because second order-neurons are sensitized

Question 25

What is responsible for allodynia?

Answer 25

Central (as in second order neuron) Sensitization

Question 26

What is the concept of central sensitization illustrated with The drug triptan?

Answer 26

When first order neuron is sensitized, then you have pain and throbbing and no allodynia
-this guy can be treated with Triptan
However, when the second order neuron becomes sensitized (the central sensitization part)
-then he or she can no longer be treated with triptan
-presents with pain, throbbing and allodynia

Question 27

Increased Iron stores in periaqueductal gray

Answer 27

Present in people with migraines vs. normal control

Iron increased with duration of illness