Lecture 40: The pathophysiology of migraine and other headaches Flashcards
What are the two types of headaches?
Primary headaches: a disorder unto itself like migraine
Secondary: a symptom of another disorder
What is migraine?
Headache + -unilateral, pulsating quality -photo/phonophobia -nausea or vomiting -aggravated by movement Can also have aura
What is aura?
A fully reversible visual, sensory or speech disturbance
Example: seeing kaleidoscopes
Lasts between 5-60 mins
If a patient presents with aura (seeing kaleidoscopes), what type of headache should you think about?
Migraine (second phase of migraine)
What is a tension-type headache?
Tightening quality (like something is clamping
Non-pulsatile
-not aggravated by movement
Aside from tension headaches and migraines, what do other primary headaches present with?
Autonomic features (watery eye, droopy eyelid, runny nose)
Side-locked features
Examples: Cluster headache, paroxysmal hemicranias
What are chronic headaches?
The chronic form of primary headaches
-associated with a high frequency for at least several months
What causes pain at the back of your head?
C2 cervical root via the occipital nerve
What is the epidemiology of headache?
Episodic tension-type headache = 40%
Migrains = 18% in women and 6% in men
What are the areas of the head that are sensitive to pain?
- Face (trigeminal and C2)
- scalp
- Dura
- Arteries
- Venous sinus
Opthalmic branch is responsible for pain sensation in these structures
Why do patients often report pain in forehead/behind their eyes?
Because ophthalmic branch of trigeminal nerve innervates pain sensation for all the intracranial structures…this is a referred pain
What is the pathway for painful messages coming from the head?
Afferents in trigeminal ganglion spinal trigeminal tract nucleus caudalis of spinal trigeminal VPM S1
Why do patients with migraine feel pain in back of head?
Because the spinal trigem nucleus receives input from the occipital area innervated by C2
How do you explain the symptoms besides pain that comes with migraine?
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
What is the trigeminocervical complex (TCC)?
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
What is Vascular theory of headache?
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)
What is the pathophysiology of migraine (neurovascular theory)?
- Abnormal cortical activity
- Cortical Spreading Depression
- Activation/Sensitization of Trigeminovascular System
4a. Abnormal brainstem activity
4b. Central Sensitization - Pain and other symptoms
What initiates migraine? Genetic component?
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
What is Familial Hemiplegic Migraine?
Symptoms: Headache, aura, MOTOR WEAKNESS
-associated with 3 genes (CACNA1A, ATP1A2 and SCN1A)
Example of heritable migraine
What leads to hyperexcitability?
- hormones (like menstruation
- stress, diet, sleep change, sensory stimuli
Leads to abnormal cortical activity
What is cortical spreading depression?
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
So what is the theoretical connection between CSD and trigeminal activation?
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
Where does the pain come from?
The activation and sensitization of the trigeminovascular system
-involves transmission of signals from the trigeminal nerve and nucleus
What is responsible for central sensitization?
Aberrant sensitization of the second order neuron
Consequence: messages of normal touch from A-beta fibers become painful because second order-neurons are sensitized
What is responsible for allodynia?
Central (as in second order neuron) Sensitization
What is the concept of central sensitization illustrated with The drug triptan?
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
Increased Iron stores in periaqueductal gray
Present in people with migraines vs. normal control
Iron increased with duration of illness
