FINAL REPORT: Glial Activation and the Chronification of Migraine

Summary

The brain is composed of neurons and glia. In fact, glia are three quarters of the cells in the brain. To date, most of the studies of the pathophysiology of headache have focused on the neurons. We studied the activation of glia in the area of the brain that processes sensory information in a rat model of chronic daily headache (CDH). We compared activation following chronic stimulation to the effect of a single painful stimulus. Repeated, episodic activation models the progression of episodic headache to chronic daily headache. This chronic state is stable long after the last stimulation (more than 8 weeks).

We measured the activation of two types of neuroglia (astrocyte and microglia) in the area of the brain that is the first level of sensory information processing, the trigeminal nucleus caudalis (TNC). The results of this study demonstrate that repeated activation leads to persistent activation of both astrocytes and microglia, and that treating the rats with a drug known to prevent the activation of the neuroglia blocks the progression to chronicity.

Hypothesis vs. findings

The overall aim of the study was to test the hypothesis that activation of neuroglia in the trigeminal nucleus caudalis contributes to the development of chronic facial allodynia in a rat model of CDH. We discovered that a consequence of this persistent neuroglia activation is an increase in permeability of the Blood Brain Barrier (BBB). We demonstrated that blocking glia activation blocks increases in trigeminal allodynia and increases in BBB permeability.

Unanswered Questions

There are many unanswered questions from this study. Pursuing the answers will significantly contribute to our understanding of the pathophysiology of chronic daily headache and its treatment. The questions are:

1. What are the consequences of glial activation on trigeminal pain sensitivity in humans?
2. What cytokines or chemokines are released by these activated neuroglia that lead to increases in trigeminal excitation?
3. Is the increased BBB permeability induced by glial activation functionally relevant in humans with CDH, and does it have implications for treatment?

What this Research Means to You

Our study of the effects of glial activation in the brain following painful stimulation of the dura demonstrates that treatments designed to reverse this activation could be beneficial to migraine sufferers.

Learn More

Michael Oshinsky, PhD, combines a passion for science with a desire to help migraine sufferers. In 2007, MRF recognized his groundbreaking work in understanding chronic headache by funding his project, Glial Activation and the Chronification of Headache.

Dr. Oshinsky always knew he wanted to be a scientist. Though his earliest interest was in entomology, the study of insects, in college and graduate school he studied computational neural circuits – how local changes globally affect neurological systems. Although his early research focused on invertebrates, such as crabs, Dr. Oshinsky knew he wanted to concentrate on research that would benefit people. Once the science and techniques had advanced to the point that his work could be applied to more complex systems, Dr. Oshinsky began studying the human nervous system.

Dr. Oshinsky was formerly an assistant professor in the Deparment of Neurology at the Thomas Jefferson University, where he worked closely with doctors at the Jefferson Headache Center to study the most complicated areas of headache medicine. While observing in the headache clinic, he found that managing chronic headache was the most common complaint. Chronic headache, which affects 4% of the general population, is a headache condition that evolves from episodic to occurring more than 15 days per month. Dr. Oshinsky’s research focused on understanding chronic headache. He investigated how episodic headaches activate brain cells called glia and whether repeated inflammation can cause permanent glial changes, which he thinks may be responsible for chronic headaches.

Dr. Oshinsky believes that interacting with headache patients is an important part of his work. Many of the patients he meets are frustrated because their treatments have not worked. He hopes that one day research will advance so that sufferers will be confident that they can be treated effectively. In his spare time, Dr. Oshinsky enjoys spending time with his children, whom he tries to “inspire to make a difference.”

Dr. Oshinsky is now the Program Director of the Extramural Research Program at the National Institute of Neurological Disorders and Stroke, the branch of the NIH that focuses on neurological diseases.