Chronic migraine: hope for a new treatment

Better understand migraine to better treat it. US researchers at the University of Illinois at Chicago have discovered a potential new cellular mechanism for the occurrence of chronic migraines that offers a new way to treat them. In a study presented on April 15 in the journal eLifethey describe how the inhibition of the HDAC6 protein restores the neuronal complexity, the attenuation of which is at the origin of the onset of chronic migraines.

The key lies in the process of neuronal plasticity

To fully understand this mechanism, we must first know how neuronal plasticity works, which covers the process of formation and deformation of connections between nerve cells. This plasticity is essential to both the causes and cures for central nervous system disorders such as depression, chronic pain, and substance abuse.

In detail, the structure of a cell is maintained by its cytoskeleton which is composed of a protein, tubulin. This is in a constant state of flux in order to change the size and shape of the cell as it activates and deactivates. This dynamic property of the cell allows the nervous system to adapt to its environment. Tubulin is modified by a chemical process called acetylation and tubulin is then said to be acetylated. This promotes a flexible and stable cytoskeleton. But in the opposite case, where the tubulin is deacetylated, this leads to instability of the cytoskeleton and plays a role in the onset of migraines. This mechanism is caused by histone deacetylase 6, or HDAC6, which is a basic protein.

The HDAC6 protein in question

In this study, conducted on mouse models, the researchers showed that inhibiting the HDAC6 protein restores tubulin acetylation and the flexibility of the cytoskeleton. This leads to reversing the cellular correlates of migraine and relieving the associated pain. “This work suggests that the chronic migraine state may be characterized by diminished neuronal complexity and that the restoration of this complexity could be a feature of anti-migraine treatments. This work also forms the basis for the development of HDAC6 inhibitors as a new therapeutic strategy for migraine.”, rejoiced Amynah Pradhan, professor of psychiatry at the University of Illinois and lead author of the study.

This new model somehow “resets” the brain back to its pre-chronic migraine state. “Blocking HDAC6 would allow neurons to restore their flexibility so that the brain is more receptive to other types of processingspecifies Amynah Pradhan. We believe that people with chronic migraines have diminished neural flexibility. If we can restore that complexity, we might be able to make him more receptive to pain management therapies..”

HDAC6 inhibitor treatments are currently in development for cancer and this protein has been identified in other types of pain. “This opens up the possibility of something we should be looking at on a larger scale.concluded the researcher. These changes may be a feature of all kinds of chronic pain conditions.”