Researchers may have found a new way to treat chronic migraine by discovering a potential new cellular mechanism for migraines. Associate professor of psychiatry at the University of Illinois Chicago Amynah Pradhan, senior author of the study said that their goal was to identify a new mechanism of chronic migraine and propose a cellular pathway for migraine therapies. The study is published in eLife. 

Their research’s focus was on the neurobiology of pain and headache and explained that the dynamic process of routing and rerouting connections among nerve cells, called neural plasticity, is critical to both the causes and cures for disorders of the central nervous system such as depression, chronic pain, and addiction.

Posted on Science Daily, the study read that the structure of the cell is maintained by its cytoskeleton which is made up of the protein, tubulin. Tubulin is in a constant state of flux, waxing and waning to change the size and shape of the cell. This dynamic property of the cell allows the nervous system to change in response to its environment.

Tubulin is modified in the body through a chemical process called acetylation. When tubulin is acetylated it encourages a flexible, stable cytoskeleton; while tubulin deacetylation -- induced by histone deacetylase 6, or HDAC6, promotes cytoskeletal instability.

Studies in mice models show that decreased neuronal complexity may be a feature, or mechanism, of chronic migraine, Pradhan said. When HDAC6 is inhibited, tubulin acetylation and cytoskeletal flexibility are restored. Additionally, HDAC6 reversed the cellular correlates of migraine and relieved migraine-associated pain, according to the study.

"This work suggests that the chronic migraine state may be characterized by decreased neuronal complexity, and that restoration of this complexity could be a hallmark of anti-migraine treatments. This work also forms the basis for the development of HDAC6 inhibitors as a novel therapeutic strategy for migraine," the researchers report.

Pradhan said this research reveals a way to possibly reset the brain toward its pre-chronic migraine state. "Blocking HDAC6 would allow neurons to restore their flexibility so the brain would be more receptive to other types of treatment. In this model we are saying, maybe chronic migraine sufferers have decreased neuronal flexibility. If we can restore that complexity maybe we could get them out of that cycle," she said.

Once out of the cycle of decreased neuronal complexity, the brain may become more responsive to pain management therapies, Pradhan said. HDAC6 inhibitors are currently in development for cancer, and HDCA6 as a target has been identified for other types of pain.

"It opens up the possibility of something we should be looking at on a broader scale," she said. "Are these changes may be a hallmark of all sorts of chronic pain states?" Migraine is a common brain disorder that is estimated to affect 14% of the world population. Current U.S. cost estimates for migraine are as high as $40 billion annually. One particularly debilitating subset of migraine patients is those with chronic migraine, defined as having more than 15 headache days a month. Migraine therapies are often only partially effective or poorly tolerated, creating a need for more diverse drug therapies.

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