Headache Pathophysiology

Question 1

what’s difference between primary and secondary headache?

Answer 1

Primary: a disorder unto itself like migraine
Secondary: a symptom of another disorder - after trauma for example

Question 2

what are examples of primary headaches?

Answer 2

cluster, tension-type and migraine

Question 3

what is the definition of migraine?

Answer 3

Headache +
 > or equal  2 of these characteristics
- Unilateral (can be bilateral in kids)
- Pulsating quality
- Moderate-Severe
- Aggravated by movement

1 or more of these associated features
-Nausea or vomiting- Photo and phonophobia

Question 4

what is aura?

Answer 4

Fully reversible visual, sensory, speech disturbance

Aura has 2 or more of the following

• Unilateral
• Develops over _5 minutes
• Lasts between 5-60 min

preceeds 20% of migraines

Question 5

what is a tension-type headache?

Answer 5

Headache lasts 30min _ 7 days
with 2 or more of these characteristics
- Bilateral
- Non-pulsatile/tightening quality
- Mild-Moderate
- Not aggravated by movement
- Does not have associated features of migraine

Question 6

what were the other examples of primary headaches? (4 - I don’t think we need to know these)

Answer 6

Side-locked and/or autonomic features

• Hemicrania Continua
• Cluster Headache
• Paroxysmal Hemicrania
• Short-lasting Unilateral Neuralgiform Headache with Conjunctival Injection and Tearing (SUNCT)

-vary in the amount of time headaches lasts

Question 7

how common are headache disorders?

Answer 7

one year prevalance of migraine - 18% women, 6 % men (different due to hormones)
episodic tension-type - 40% both men & women
frequent headaches - 5% women, 3% men

Question 8

what nerve is responsible for relaying sensory and pain information from the face?

Answer 8

trigeminal

Question 9

what nerve is responsible for Sensation and pain from the back of the head

Answer 9

C2 via occipital nerve

Question 10

what other areas on the head are sensitive to pain?

Answer 10

the scalp, the dura, the arteries and the venous sinuses.

Question 11

what nerve is responsible for pain from scalp, dura, and others?

Answer 11

ophthalmic branch of the Trigeminal Nerve.

This overlap is important when we consider why patients often report pain in their forehead and behind their eyes, when in fact that pain is referred from an intracranial process

Question 12

how are painful messages transmitted in headaches?

Answer 12

Painful messages are relayed through the trigeminal ganglion, down the spinal trigeminal tract to the nucleus caudalis, which is a subdivision of the spinal trigeminal nucleus.

Question 13

why can headache pain be felt on the back of the head?

Answer 13

The spinal nucleus is a hub of communication with other cranial nerves and with messages from the occipital area innervated by C2.

Question 14

where do fibers go from nucleus caudalis?

Answer 14

Fibers from the nucleus caudalis then cross and ascend in the trigeminothalamic tract to the ventral posteromedial (VPM) nucleus of the thalamus, and then the messages are relayed to the somatosensory cortex.

Question 15

what other nuclei does spinal trigeminal nuclei make connections with?

Answer 15

1) the superior salivatory nucleus, is involved in the parasympathetic system, and it plays a role in blood vessel dilatation as well as autonomic symptoms that can accompany headache.
2) The spinal nucleus also makes ascending connections with the hypothalamus, which explains why there are changes in appetite and sleep during the headache.
3) the spinal nucleus projects to the posterior nucleus of the thalamus, which in turn projects to multiple association areas of the cortex. These contribute to disturbances in neurological functions involved in vision, hearing, memory, motor, and cognitive performance during the headache.

*noted in slide we don’t need to know these details - just that anatomy explains symptoms of migraine

Question 16

what is the vascular theory?

Answer 16

vasoconstriction of the cerebral vessels led to
decreased cerebral bloodflow –> symptoms of aura and simultaneous compensatory vasodilation of blood vessels –> perivascular inflammation which causes headache.

Question 17

what is the evidence for & against vascular theory?

Answer 17

Evidence supporting this:
_ Vasodilators in migraineurs trigger migraine HA
_ Vasoconstrictors relieve migraine HA
_ Migraine is associated with some vasculopathies
Evidence against this:
_ Functional imaging has shown that regional blood flow decreases during aura, but headache often starts before normalization of blood flow
_ Vasodilation of meningeal and/or extracranial arteries is neither necessary nor sufficient for migraine pain

Question 18

what are five steps in pathophys of migraine ?

Answer 18

1) abnormal cortical activity
2) corical spreading depression
3) activation/sensitization of trigeminovascular system
4) abnormal brainstem activity
5) central sensitization

Question 19

what is abnormal cortical activity?

Answer 19

people with migraines have hyperexcitable brains - heightened reactivity to sensory stimuli. (stress, sleep, diet changes, sensory stimuli trigger migraine)

Simple things like disrupted sleep or alcohol can trigger the cascade of events that will lead to a migraine in someone who is susceptible, but similar triggers will not cause headache in someone without this predisposition.

Question 20

are migraines genetic?

Answer 20

yes- high rate of concordance in mono vs dizygotic twins, relatives have 3x higher risk

Question 21

what is familial hemiplegic migraine?

Answer 21

uncommon type with unilateral headache, aura, and motor weakness.
-associated with three genes - all for ion channels –> increased gluatamate

Question 22

what is cortical depressing spreading?

Answer 22

is a wave of electrophysiological hyperactivity followed by a wave of inhibition, usually in the visual cortex

rate of propagation of CSD and aura are the same

Question 23

what is the mechanism of CSD?

Answer 23

unclear but the following is known:

• efflux of K+ ions
• glial glutamate transmission at sites other than synapses -> synchronization of neurons (like in seizures)
• Several medications used to prevent migraines have been shown to inhibit glutamate-induced CSD

Question 24

how does CSD sensitize/activate the trigeminal nerve? (details from notes)

Answer 24

1)CSD is accompanied by large increase in the concentration of extracellular potassium ions and protons as well as neuropeptides 2) This triggers vasodilatation of blood vessels. The perivascular axons also release neuropeptides such as substance P and calcitonin gene-related peptide, which contribute to an inflammatory soup.
3) This in turn causes mast cells to release histamine, serotonin, bradykinin, TNF-alpha, and nitric oxide, again leading to more inflammation. These inflammatory substances activate receptors that are coupled to second-messenger cascades which, in turn, modulate voltage-gated ion channels.
4) Through this mechanism, the meningeal nociceptors become hypersensitive (hence, the term sensitized), and normal fluctuations like pulsation of the blood vessels are perceived as painful.
5) The meningeal nociceptors
send these messages of pain through the trigeminal ganglion to the trigeminal nucleus caudalis.

Question 25

what is a basic understanding of how CSD sensitizes trigeminal nerve?

Answer 25

Cortical spreading depression triggers the release of several chemicals that sensitize the meningeal nociceptors. When they are sensitized, they perceive non-painful stimuli as painful.

Question 26

what is allodynia?

Answer 26

where non-painful touch is perceived as painful

Question 27

what is central sensitization? How does it occur?

Answer 27

sensitized peripheral nociceptors interpret normal blood vessel pulsation as above the threshold of pain –> release of neuropeptides like CGRP at the central terminals of the nociceptors.

As wide-dynamic range neurons in the trigeminal nerve caudalis are stimulated over and over, this leads to sensitization, meaning increased excitability, increased synaptic strength, and enlargement of the receptive field beyond the original site of inflammation.

Messages of normal touch from the A-beta fibers are then perceived as painful.

Question 28

how do triptan medicines work?

Answer 28

two methods of action depending on timing in migraine:

1) If given early in an attack, they act at both ends of the trigeminovascular neuron and block transmission of pain signals, thus stopping the pain and the throbbing sensation.
2) after allodynia set in, they are no longer effective at stopping the pain. They still act to interrupt the signal from the periphery, so can decrease the pain and stop the throbbing sensation, but do not eliminate pain nor allodynia

Question 29

how is the brainstem involved in the pathophys of a migraine?

Answer 29

many brainstem nuclei send projections to the TNC –> signals modify the effect of the message coming from the TNC.

for example periaqueductal grey matter seems to reduce pain –> PAG is activated when subjects were distracted from their pain, but not activated when they focused on their pain

Dysfunction in brainstem nuclei involved in central control of pain and central sensitization may lead to hyperexcitability of central trigeminovascular

Question 30

what is the relationship between iron in PAG and migraines?

Answer 30

ion accumulation in PAG correlates with duration of illness

-unknown why

Question 31

what are the phases of a migraine?

Answer 31

1) prodrome - can start up to 24hrs before the pain, and is the earliest warning that pain is coming. Common symptoms include mood changes, dizziness, concentration problems, neck pain, yawning, and food cravings.
2) aura comes 5 to 60 minutes before the pain, and involves vision more often than sensory changes, and rarely involved motor weakness. (only 20% of migraines)
3) headache phase can last hours to days, and is usually accompanied by sensitivity to light, sound, and smells as well as nausea.
4) postdrome is a time of headache hangover when people feel tired and unwell. This can last for a day or so.

Question 32

what part of migraine pathophys is related to prodrome?

Answer 32

Prodrome _ represents some changes in neurologic function from disruption of homeostasis in the CNS. This is not well understood, but likely relates to the hyperexcitability of the migraine brain.

Question 33

what part of migraine pathophys is related to aura?

Answer 33

reflects cortical spreading depression.

Question 34

what part of migraine pathophys is related to headache phase?

Answer 34

mild headache represents processing of initial signals of the trigeminal nerve. Headache worsens and allodynia develops with the onset of peripheral and then central sensitization.

Question 35

what part of migraine pathophys is related to postdome??

Answer 35

not well understood. Could be related to abnormal function of the brainstem.