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New Developments in Migraine  -or- ( Why do humans get so many headaches?) Stasha Gominak, M.D. East Texas Medical Center Neurologic Institute 700 Olympic Plaza, Suite 912 Tyler, Texas
Despite what we were all  taught, migraine is  not  a vascular disorder
I believe that migraine is a disorder of electrical hyper excitability of the head pain system coming from a brainstem “migraine generator”
I believe that all humans with normal head anatomy who have spontaneous head pain have “migraine”. It comes in different sizes but all with the same mechanism.
  Trigeminal Nucleus Caudalis   perceives pain for the face and the front 2/3 of the head.   Dorsal Horn C2-C4  perceives pain for the back 1/3 of the head and the neck. ,[object Object]
The pain system of the head was put there to tell us not to bang our heads.
PET Scans in Migraine Patients show that the posterior brain stem is hyper metabolic Weiller C, May A, Limmroth V, et al. Nature Med 1995;1:658-660
The migraine sufferer has a normal wiring diagram but inherits a gene that allows the pain wires to turn “on” without a blow to the head.
The Gene Mutations that Cause  Migraine
Genes that cause migraine affect the electrical excitability of brain cells ,[object Object],[object Object],[object Object]
Ca++ channel in a membrane ,[object Object],[object Object],[object Object],[object Object]
Voltage gated Ca ++ channels turn cells“on”  Ca++ pumps  turn them “off” ,[object Object],[object Object],[object Object],[object Object],[object Object],Voltage gated Ca++ channel ++ ++ ++ ++ + + + + + + +
Migraine is a Channel Disorder ,[object Object],[object Object],[object Object]
This may be why the brain stem nuclei are inappropriately “on” in migraine patients
Any migraine sufferer will tell you, (if you ask), that they go to bed not just because their head hurts but because they also “can’t think right” Migraine is not just a disorder of head pain.  Any theory about migraine has to explain this global change in brain functioning .
1960’s Magnetic Field Studies Starting with the visual aura they observed   electrical suppression, starting in the back during visual aura, moving slowly forward taking 15 minutes to go from back to front
Magnetic Field Studies electrical suppression, starting in the back during visual aura, moving slowly forward, 15 minutes to go from back to front
Magnetic Field Studies electrical suppression, starting in the back during visual aura, moving slowly forward, 15 minutes to go from back to front
Spreading Depression of Dr. Leao ,[object Object],[object Object],[object Object]
Newest Brain Discoveries that Explain Spreading Depression ,[object Object],Neuron Astrocyte
Astrocytes are more influential than previously imagined ,[object Object],[object Object],[object Object]
Spreading Depression of Leao is an inter  cellular calcium wave ,[object Object],[object Object],[object Object]
Astrocytes link blood signals to neuronal signals ,[object Object],[object Object],[object Object],[object Object]
Most headaches are “migraine” ,[object Object],[object Object],[object Object],[object Object]
What is unique about the head pain system that makes it turn on spontaneously? The other, analogous pain areas of the rest of the spinal cord don’t just switch on when ever they feel like it.
What about the other migraine symptoms? They’re not in the trigeminal caudal nucleus   ,[object Object],[object Object],[object Object]
What causes this excitation? Remember our friend the astrocyte?
Astrocytes act more as a syncytium joining all of the neurons of the brain
Migraine as an astrocyte disorder ,[object Object],[object Object]
Why would humans have so many genes to give them headaches? ,[object Object],[object Object]
Migraine and Sleep are intertwined ,[object Object],[object Object],[object Object],[object Object]
What about chronic neck pain and “tension headaches” ,[object Object],[object Object],[object Object],[object Object]
Are daily headaches migraine too? ,[object Object],[object Object],[object Object],[object Object]
Key Points of Brainstem Hyper excitability ,[object Object],[object Object],[object Object]
Sleep disorders cause migraine ,[object Object],[object Object],[object Object],[object Object],[object Object]
Hormones and Migraine
Any migraine theory has to explain: ,[object Object],[object Object],[object Object],[object Object],[object Object]
Hypothalamus GnRH Anterior Pituitary LH/FSH Ovaries inhibin, estradiol, progesterone Adapted from MacGregor EA.  Neurologic Clinics  1997;15(1):125-141. Menstruation and Releasing Hormones
Gonadotropin Releasing Hormones ,[object Object],[object Object],[object Object],[object Object],[object Object]
Children Have Headaches Too ,[object Object],[object Object],[object Object],[object Object]
Episodic Treatment: Triptans sumatriptan, naratriptan, eletriptan, etc. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Where are the Serotonin receptors ? ,[object Object],[object Object]
Serotonergic cells in Raphe Nuclei of the Periaquiductal Grey   ,[object Object],[object Object],[object Object],[object Object],Trigeminal Nucleus Caudalis
Treatment: Prevention ,[object Object],[object Object],[object Object],[object Object],[object Object]
Daily Preventatives are all Channel Stabilizers ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Are there other things like Migraine? ,[object Object],[object Object],[object Object]
Mouse models of Migraine   ,[object Object],[object Object],[object Object],[object Object],Boy do I have a Headache!
Epilepsy and Channels ,[object Object],[object Object],So this is what they meant by “knockout mouse”
Most epilepsy medications are “channel stabilizers”. They act on malfunctioning channels to make them act more normally. Which is probably why some of them are  also migraine preventatives and treat vertigo. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Can Epilepsy be like Migraine? ,[object Object],[object Object],[object Object],[object Object],[object Object]
Do animals have migraines?  (Bella can’t tell us if she has a headache.) I always get a headache when I have to ride in the car.
 
References ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
References ,[object Object],[object Object],[object Object],[object Object]

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Migraine 2010

  • 1. New Developments in Migraine -or- ( Why do humans get so many headaches?) Stasha Gominak, M.D. East Texas Medical Center Neurologic Institute 700 Olympic Plaza, Suite 912 Tyler, Texas
  • 2. Despite what we were all taught, migraine is not a vascular disorder
  • 3. I believe that migraine is a disorder of electrical hyper excitability of the head pain system coming from a brainstem “migraine generator”
  • 4. I believe that all humans with normal head anatomy who have spontaneous head pain have “migraine”. It comes in different sizes but all with the same mechanism.
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  • 6. The pain system of the head was put there to tell us not to bang our heads.
  • 7. PET Scans in Migraine Patients show that the posterior brain stem is hyper metabolic Weiller C, May A, Limmroth V, et al. Nature Med 1995;1:658-660
  • 8. The migraine sufferer has a normal wiring diagram but inherits a gene that allows the pain wires to turn “on” without a blow to the head.
  • 9. The Gene Mutations that Cause Migraine
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  • 14. This may be why the brain stem nuclei are inappropriately “on” in migraine patients
  • 15. Any migraine sufferer will tell you, (if you ask), that they go to bed not just because their head hurts but because they also “can’t think right” Migraine is not just a disorder of head pain. Any theory about migraine has to explain this global change in brain functioning .
  • 16. 1960’s Magnetic Field Studies Starting with the visual aura they observed electrical suppression, starting in the back during visual aura, moving slowly forward taking 15 minutes to go from back to front
  • 17. Magnetic Field Studies electrical suppression, starting in the back during visual aura, moving slowly forward, 15 minutes to go from back to front
  • 18. Magnetic Field Studies electrical suppression, starting in the back during visual aura, moving slowly forward, 15 minutes to go from back to front
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  • 25. What is unique about the head pain system that makes it turn on spontaneously? The other, analogous pain areas of the rest of the spinal cord don’t just switch on when ever they feel like it.
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  • 27. What causes this excitation? Remember our friend the astrocyte?
  • 28. Astrocytes act more as a syncytium joining all of the neurons of the brain
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  • 38. Hypothalamus GnRH Anterior Pituitary LH/FSH Ovaries inhibin, estradiol, progesterone Adapted from MacGregor EA. Neurologic Clinics 1997;15(1):125-141. Menstruation and Releasing Hormones
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  • 51. Do animals have migraines? (Bella can’t tell us if she has a headache.) I always get a headache when I have to ride in the car.
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Editor's Notes

  1. The hypothesis of migraine pathophysiology is consistent with the clinical observations that sinus-like symptoms often accompany migraine. Migraine is a neurovascular disorder involving activation of the TNC. Pain can be referred anywhere along the trigeminal nerve network including the sinus area. Activation of the TNC can cause reflex activation of the cranial parasympathetic nerves and thereby lead to sinus-like symptoms.
  2. But it is now recognized that during menstruation, it is more complex than just a change in estrogen and progesterone. In fact, there are multiple migraine triggers (eg, sleep, light, weather, foods, etc) as well as multiple neurotransmitters that are involved. Multiple things can occur during the menstrual cycle that can trigger a migraine. This makes sense, when one considers the fact that the majority of female migraineurs experience migraines outside of the menstrual cycle as well as within the cycle. For these reasons, simply treating with hormones is often inadequate, especially across attacks and across people.