Brian M. Plato, DO Norton Headache and Concussion Center Norton Neuroscience Instittute

1. The Science of Migraine
Brian M. Plato, DO
Norton Headache and Concussion Center
Norton Neuroscience Institute

2. A Common Problem
• 45 million Americans with headache disorders
• 30 million Americans with migraine, the most
common disabling form of headache
• 12% of the US population has migraine
• 18% of women, 6% of men are affected by
migraine

3. One Year Prevalence of Migraine
Lipton R B et al. Neurology 2007;68:343-349

4. Migraine is more common than
diabetes and asthma combined!
1%
7%
6%
7%
13%
0% 5% 10% 15% 20%
Migraine
Osteoarthritis
Diabetes
Asthma
Rheumatoid
Arthritis

5. Commonly Mis- / Un-Diagnosed
Diagnosed Migraine
Undiagnosed
Migraine
39%
61% 52%
48%
1989
1999
Lipton et al., 2001
American Migraine Study II

6. A Costly Problem
• Chronic headache disorders are among the
top 20 causes of disability in the US according
to the World Health Organization (WHO)
• 4% of Americans experience 4 hours of
headaches per day, at least 15 days per month
• Headache disorders are responsible for more
than $31B in economic costs in the US
annually

7. Diagnosis of Migraine Without Aura
• No single feature required or sufficient for diagnosis
• Characteristics (2/4)
– Unilateral (40% bilateral or generalized)
– Throbbing (50% non-pulsating)
– Moderate-severe intensity (~20% mild)
– Pain worsened by exertion (>95%)
• Associated symptoms (1/2)
– Nausea (86% – 95%) or vomiting (47% – 62%)
– Photophobia (82% – 95%), phonophobia (61% – 98%)
Russell MB et al. Cephalalgia. 1996.
Pryse-Phillips WEM et al. Can Med Assoc J. 1997.

8. Additional Features of Migraine
• Predictable timing around menstruation and
ovulation
• Stereotyped prodromal symptoms
• Characteristic triggers
• Improves with sleep (more effective in young pts)
• Positive family history
• Childhood precursors (cyclic vomiting, abdominal
“migraine”, episodic vertigo, probably motion
sickness)
• Osmophobia (smell sensitivity)

9. “I have sinus headaches”
Eross E, Dodick D, Eross M. The sinus, allergy and migraine study (SAMS)
86% Migraine
3% Sinus related headache
Patients self diagnosing “sinus headaches”

10. What Causes Migraine?
• The Vascular Theory
• Blood vessels constricting (aura)
Followed by
• Blood vessels dilating

11. The Vascular Theory
• Does not explain prodrome
• Not supported by blood flow studies
• There are effective nonvascular drugs, such as
NSAIDs
• Most patients do not have aura
• THIS IS NOT CORRECT

12. The Neurovascular Theory
• Referred pain from dura mater and blood
vessels
• Peripheral Neural Processing
• Central Neural Processing

13. Pain Perceiving Structures Inside the Skull
The most important structures that register pain in the head are the large cranial vessels,
proximal cerebral vessels and dural arteries and the large veins and venous sinuses

14. A More Sensitive Brain
Pain control mechanisms are partially defective in migraine patients

15. Wang, Schoenen. Cephalalgia. 1998.
People with migraine process visual and auditory stimulation differently that people
without migraine. In this example with repeated stimulation non-migraine patients
have decreased response with repeated stimulation whereas migraine patients have
an increased response.

16. Migraine Aura

18. Migraine Aura
• A reversible focal neurological deficit
– Most commonly visual
• Cortical spreading depression
– Think a wave of activity moving across the brain
followed by decreased activity
– The part of the brain inactivated causes the
neurological deficit
• Occipital lobes = vision

19. Spreading Depression of Leão
EEG activity is suppressed and moves in a wave, correlates with symptoms

20. Aura is from brain cells (neurons)

21. The Pain

23. Neuropeptides
• Cranial levels of both substance P and
calcitonin gene-related peptide (CGRP) are
increased by stimulation of the trigeminal
ganglion in humans
• In migraine CGRP is elevated in external
jugular vein blood, whereas substance P is not
• CGRP infusions can trigger headache and
migraine

24. A Growing Snowball
• Trigeminal nerve and its blood supply
(neurovascular)
– Release of neuropeptides
• CGRP
• Substance P
• 5-HT (serotonin) --> “triptans”
• Nitric oxide
– Vasodilatation (CGRP) leads to further activation, and the
process spreads
– Brainstem, thalamus, cortex become activated leading to
“central sensitization”
• Amplified pain signaling in the central nervous system
– Allodynia: pain due to a non-noxious stimulant

25. Cutaneous Allodynia
Migraineurs develop increased
sensitivity to stimuli as a result of
increased nerve excitability
80% of migraine patients had
cutaneous allodynia during attacks
Non painful stimuli perceived as
painful
After allodynia occurs, triptans lose
effectiveness

26. Burstein R, et al. Brain. 2000.
1-Peripheral
Trigeminal Sensitization
2-Central Trigeminal
Sensitization
3-Forehead Allodynia
4-Extracephalic
Allodynia

27. Importance of treating early
No Allodynia Allodynia
Pain free @2hrs 28 (93%) 5 (15%)
Not pain free @2hrs 2 (7%) 29 (85%)
30 34
R Burstein, 2003

28. Allodynia is a risk factor for
developing chronic migraine

29. Earliest Possible Treatment to Stop
Migraine Progression and Chronification
Inherited
threshold for
trigeminal
activation
Triggers or
stressors
Episodic
migraine
Ineffective
pain
control
Medication
overuse
Increased
headache
frequency
Chronic
migraine
Graphic adapted from: Calhoun AH. In: Headache Newsletter: American Headache Society
Committee for Headache Education; Veteran’s Day, 2010.

30. Medication Overuse Headache
• Headache present on ≥15 days/month
• Regular overuse for ≥3 months of one or more drugs
that can be taken for acute and/or symptomatic
treatment of headache
• Headache has developed or markedly worsened
during medication overuse
• Headache resolves or reverts to its previous pattern
within 2 months after discontinuation of overused
medication

31. Chronification of Migraine
Medication Overuse Headache
The Cleveland Clinic Manual of Headache Therapy p. 156
Bigal ME, et al. Headache. 2008;48:1157-1168.
Bigal ME, et al. Pain. 2009;142:179-182.

32. Medication Overuse Headache
• Simple analgesics:
• Acetaminophen (Tylenol)
• Ibuprofen (Advil, Motrin)
• Aspirin (Bayer)
• Naproxen (Aleve)
• Combination products:
• Fioricet
• Excedrin
• Opiates:
– Lortab (hydrocodone)
– Percocet (oxycodone)
– Many others
• Triptans:
– Imitrex, Maxalt, Relpax,
Zomig, Frova, Amerge,
Axert, Treximet
• DHE

33. Why opiates are bad

34. Other Associated Symptoms

35. Nausea
• Gastroparesis occurs frequently,
both during and outside of acute
migraine attacks1-3
– May correlate with intensity of
headache, nausea, and photophobia4
• Absorption of orally administered
drugs used to treat migraine may be
delayed by gastroparesis,
postponing the drug’s onset of action1,5-7
1. Krymchantowski AV, et al. Cephalalgia. 2006;26(7):871-874; 2. Aurora SK, et al. Headache. 2006;46(1):57-63; 3. Aurora
S, et al. Headache. 2007;47(10):1443-1446; 4. Boyle R, et al. Br J Clin Pharmacol. 1990;30(3):405-409; 5. Thomsen LL, et
al. Cephalalgia. 1996;16(4):270-275; 6. Volans GN. Br J Clin Pharmacol. 1975;2(1):57-63; 7. Tokola RA and Neuvonen PJ.
Br J Clin Pharmacol. 1984;18(6):867-871; 8. Tfelt-Hansen P. Headache. 2007;47(6):929-930; 9. Dahlöf C. Curr Opin
Neurol. 2002;15:317-322; 10. Lychkova AE. Bull Exp Biol Med. 2004;138(2):127-130.

36. Other Associated Symptoms
• Blurry vision (29%)
• Neck pain (31%)
• Nasal congestion (28%)
• Sweating (30%)
• Dizziness (16%)

37. Why is it important to understand
the science of migraine?
• Treatment
– Prevention of triggers
– Preventative medications
– Rescue medications

38. Triggers
• We now understand that patients with
migraine have an “excitable” brain
– Need to be careful with:
• Sleep
• Diet
• Medication overuse
• Stress management

39. Preventative Medications
• Antiseizure drugs
– Topamax
– Depakote
• Antidepressants
– Amitriptyline (Elavil)
– Effexor
• Blood pressure medications
– Propranolol (Inderal)
– Verapamil

40. Rescue Medications
• Triptans
• NSAIDs
• DHE

41. Triptans
Selective agonists (activators) of serotonin
blocking the release of other inflammatory
chemicals during a migraine attack
Triptans work here

42. Triptans
• Prevent release of neuropeptides
• Once enough activation has occurred the
process of central sensitization begins
– Manifested by allodynia
– Remember 15% vs. 93% chance of success

43. NSAIDs
• Ketorolac infusion has been shown to reverse
central sensitization
• IV ketorolac is not practical in the outpatient
setting
• Ibuprofen, naproxen, diclofenac

44. DHE
• Can also reverse central sensitization
• More side effects
• A little less convenient to give in the home
setting

45. Summary
• Hyperexcitable brain: more susceptible to
triggers
• Aura: spreading excitation and depression
• Throbbing head pain: trigeminal inflammation
• Allodynia: common, important and due to
central sensitization

46. Learn More at Headache School
• Women and Headaches
• June 13 • 6 to 7:30 p.m.
• Biofeedback and stress
management
• July 11 • 6 to 7:30 p.m.
• Headache related to injury
• August 8 • 6 to 7:30 p.m.
• What is a migraine aura?
• September 12 • 6 to 7:30
p.m.
• Alternative headache
treatments
• October 17 • 6 to 7:30 p.m.

47. Thank you!