This presentation was given to first year pharmacy students as a part of course on a medical physiology and pathophysiology.

1. Headache & Migraine
Brian J. Piper, Ph.D., M.S.
October 23, 2012

2. Goals
• Describe differences in symptomology
between migraines, cluster headaches, and
tension-type headaches.
• List the vascular and neural substrates of
migraine/headaches.

3. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5503a6.htm

4. Importance
• WHO ranks migraine among world’s most
debilitating chronic illnesses
• 3rd most common reason for ER visits (U.S.)
• ≈$13 billion/year in lost productivity (U.S.)
• underdiagnosed & undertreated
Menken et al. (2000). Archives of Neurology, 57(3), 418-420.

5. Migraine Terminology
• migraineurs: person who experiences migraines
• aura: collection of symptoms that may precede or
co-occur; typically visual, lasts less than 1 hour
– positive features
• scintillations: a rapidly oscillating pattern of visual distortions
• photopsia: perception of flashes of light
• teichopsia: spot of flickering light
– negative features
• scotoma: an area of diminished vision within the visual field
• hemianopsia: blindness in half of the visual field, may involve
one or both eyes
– hemiplegic aura: occurring on one side of body
– basilar type aura: aura is localized to the brainstem
DiPiro et al. (2008). Pharmacotherapy: A Pathophysiologic Approach. p. 1008.

6. George Cruikshank: The Head Ache (1819)
2:20: http://www.mayoclinic.com/health/migraine-aura/MM00659

7. International Headache Society Migraine Criteria
• Migraine with aura (classic migraine)
– At least 2 attacks
– Aura fulfills criteria for typical aura, hemiplegic aura, or basilar
type aura
– Not attributed to another disorder
• Migraine without aura
– At least 5 attacks
– Headache lasts 4 to 72 hours (untreated or successfully treated)
– Headache has at least 2 characteristics
• Unilateral location, pulsating quality, or moderate or severe intensity
– Aggravation by or avoidance of routine physical activity
(walking, climbing stairs)
– During headache, at least one of the following:
• Nausea, vomiting, or both
• Photophobia and phonophobia
– Not attributed to another disorder
http://ihs-classification.org/en/02_klassifikation/02_teil1/01.00.00_migraine.html

8. Epidemiology: American Migraine
Prevalence & Prevention Study
• Mailed Survey to 257K, response by 163K (64.9%) who
are representative of U.S. population
• Migaine: IHS criteria, Chronic Migraine: >15 days/month
over 3 months

9. Epidemiology: American Migraine
Prevalence & Prevention Study
• Mailed Survey to 257K, response by 163K (64.9%) who
are representative of U.S. population
• Migraine: IHS criteria, Chronic Migraine: >15 days/month
over 3 months

10. Epidemiology: American Migraine
Prevalence & Prevention Study
• Mailed Survey to 257K, response by 163K (64.9%) who
are representative of U.S. population
• Migraine: IHS criteria, Chronic Migraine: >15 days/month
over 3 months
• Demographic Correlates
– Age (18-49)
– Sex (Female)
– SES: >$90K = 0.52; <$22K = 2.71; 5.2 fold!
• Primary versus Secondary (tumor, infection, stroke)
Buse et al. (2012-in press). Headache. doi: 10.1111/j.1526-4610.2012.02223.x

11. Pathophysiology
• limited animal models
• theory: genetic (50% heritable) & neurovascular
• 2 min: http://www.youtube.com/watch?v=yZr9Joe85wg
• orthodromic: electrical potential following typical direction (soma
to axon)
• antidromic: electrical potential traveling in the reverse direction
(axon to soma)

12. Neural Substrates of Migraine
• 1) meningeal vessels
• 2) trigeminal: opthalmic nerve (V1)

13. Neural Substrates of Migraine
• 1) meningeal vessels
• 2) trigeminal: opthalmic nerve (V1)
• 3) pons (input from other structures)
• 4) facial nerve

14. Neural Substrates of Migraine
Goadsby et al. (2002). New England Journal of Medicine, 346(4), 257-270.

15. 5-HT1B: vasoconstriction
5-HT1D: peripheral neuronal inhibition
Goadsby et al. (2002). New England Journal of Medicine, 346(4), 257-270.

16. Brainstem Activation During Migraine
Posterior
• 43 year old man with history of
migraine without aura
• Positron Emission Tomography
completed at rest and
following nitroglycerin
Anterior
Bahra et al. (2001). Lancet, 357, 1016-1017.

17. Migraine Across Countries (Twins)
Mulder et al. (2003). Twin Research, 6(5), 422-431.

18. Genetic Contribution to Migraine
Mulder et al. (2003). Twin Research, 6(5), 422-431.

19. Environmental Factors
stress
head and neck infection
head trauma/surgery
Hormone changes
aged cheese
dairy
red wine
nuts
shellfish
caffeine withdrawal
vasodilators
perfumes/strong odors
irregular diet/sleep
light

20. Cluster Headache
• unilateral pain
• unilateral other:
– ptosis
– miosis
– rhinorrhoea
• circadian
• males > females
• brief ( < 3 hours)
• rare
Dodick et al. (2001). Cluster headache. Cephalagia, 20(9), 787-803.
http://ihs-classification.org/en/02_klassifikation/02_teil1/03.01.00_cluster.html

21. Hypothalamic & Insular Activation
During Cluster Headache
• 9 patients with a history of cluster completed
PET for regional cerebral blood flow at rest &
following nitroglycerin
May et al. (1998). Lancet, 352(9124), 275-278.

22. Episodic Tension-type Headache
(TTH)
A. Number of days with such headache < 180/year (<15/month)
B. Headache lasting from 30 minutes to 7 days
C. At least 2 of the following:
• Pressing/tightening (non-pulsating) quality
• Mild or moderate intensity (may
inhibit, but does not prohibit activities)
• Bilateral location
• No aggravation by walking stairs
or similar routine physical activity
D. Both of the following:
• No nausea or vomiting (anorexia may occur)
• Photophobia and phonophobia are absent, or one but not
the other is present
E. At least 10 previous headache episodes fulfilling these criteria
F. No evidence of organic disease

23. D
Substrates of TTH
V
Dorsal Horn: sensory
Ventral Horn: motor

24. Tension-type Headache or Migraine
Mild
Moderate
Severe Aura
Unilateral
Vomiting
Bilateral
Photophobia Aggravated
by Activity
Nausea
Throbbing
Pressure
Tension-Type Migraine

25. Comparison
• Frequency: TTH > Migraine > Cluster
• Pain:
• Sex Ratio: F > M F>M M>F

26. Summary
• Headache and migraine are common but
under-appreciated.
• Migraine & headache pathophysiology is an
active, but far from complete, area of
research.
0 to 1.5 min (skip ad): http://www.youtube.com/watch?v=eJZMnXG_Yw0

27. Medication Overuse Headache
• Occurrence of rebound headache following
long-term treatment
• Identification may take months, may involve
transition to prophylactic treatment (e.g. SSRI)
Smith & Stonerman (2004). Drugs, 64(22), 2503-2514.