Scientists have long been puzzled by the connection between migraines and auras, which are neurological symptoms that precede or occur during migraines. However, a recent study on mice suggests that the way the brain communicates with peripheral nerves may hold the key to understanding this phenomenon.
More than 1 billion people worldwide experience migraines each year, with about one-quarter of them having migraines accompanied by auras. These auras can manifest as sensory disturbances such as visual or auditory hallucinations, tingling sensations, or numbness. Researchers have linked these auras to “cortical spreading depression,” abnormal waves of activity in the brain that temporarily deactivate certain neurons, triggering pain-detecting nerves outside the brain.
Previously, it was unclear how the chemicals responsible for these events reached the nerves. In a study published in the journal Science, scientists investigated the route through which molecules can escape the brain’s protective barrier. By focusing on a group of neurons known as the trigeminal ganglion, which transmits signals from the nerves in the face and jaw to the brain, researchers discovered that this nerve bundle serves as a pathway for cerebrospinal fluid (CSF) and its components to exit the brain.
Using genetically modified mice with neurons that illuminate in the presence of calcium, a crucial element for neuronal signaling, researchers injected a tracer into the mouse’s brain to track the flow of CSF. They found that the fluid entered the trigeminal ganglion shortly after injection, leading to increased calcium-driven activity. This provided direct evidence that CSF can carry molecules out of the brain through this channel.
The study also revealed that during cortical spreading depression, there was an elevated flow of CSF carrying proteins and other molecules to the trigeminal ganglion, many of which were associated with pain and inflammation. These findings suggest that the release of pain-triggering molecules into the CSF during an aura phase could activate sensory nerves in the trigeminal ganglion, contributing to the development of migraine headaches.
While current migraine therapies target a protein called calcitonin gene-related peptide (CGRP), which activates pain-sensing nerves, the study identified additional proteins that could offer new treatment possibilities. By understanding the mechanisms involved in migraine onset, researchers hope to develop more effective therapies for individuals who do not respond well to existing treatments.
Although the experiments were conducted in mice, researchers are eager to investigate these processes in humans or more human-like animal models to validate their findings. By exploring the role of these newly identified pain-triggering proteins in migraines and other headache disorders, researchers aim to develop innovative diagnostic tools and treatment options for a broader range of patients.
