Health

Scientists Discover "Missing Link" Causing Headaches

Scientists Discover

For years, scientists have wondered how migraines can lead to auras, which are short-term neurological symptoms that arise before or during a migraine. However, a new study seems to have solved this mystery. The study, conducted on laboratory mice, identified a newly discovered pathway that explains how the brain communicates with peripheral nerves, potentially offering answers to scientists about a migraine condition affecting over a billion people annually.

Researchers have known that these auras are linked to "cortical spreading depression," a wave of abnormal activity that floods the brain and temporarily disrupts certain neurons. It is also believed that these waves somehow interfere with the nerves that sense pain outside of the brain, partly by releasing chemicals into the cerebrospinal fluid (CSF), a substance that surrounds the organ and mitigates its shock.

Recently, scientists managed to discover a route through which certain molecules can escape the brain's protective barrier. In the study published in the journal Science, researchers examined the path of cerebrospinal fluid leaving the brain by focusing on a set of neurons known as the trigeminal ganglion. This bundle of cells conveys signals from the facial and jaw nerves to the brain and is connected to the brainstem.

They found that this nerve bundle also provides a pathway for cerebrospinal fluid and the molecules within it to access the outside world from the brain. The researchers used genetically modified lab mice that produce neurons glowing in the presence of calcium, as calcium is an essential element used by brain cells to send electrical signals. While monitoring the trigeminal ganglion, the researchers injected a tracing substance into the mouse's brain to track the flow of cerebrospinal fluid. They also introduced a substance that allowed calcium to flow into the neurons, activating them.

The experiment demonstrated that cerebrospinal fluid appeared in the trigeminal ganglion about four minutes post-injection, followed by a sharp increase in calcium-driven activity. This provided direct evidence that cerebrospinal fluid can carry molecules out of the brain through this channel. It is likely that the fluid interacts with the ganglion near the brainstem, where the ganglion lacks the tightly cohesive outer barrier seen elsewhere along its length.

To connect the dots with migraines, the team examined the effects of cortical spreading depression. They found that it can increase the flow of cerebrospinal fluid in the affected area, carrying more proteins and other molecules to the trigeminal ganglion than it typically does. Many of these proteins are pain and inflammation drivers.

Martin Kagh Rasmussen, a researcher at the University of Copenhagen, noted that "during the aura, proteins are released that can activate and stimulate sensory nerves to the cerebrospinal fluid and transport them to the trigeminal ganglion, where they activate the pain-transmitting sensory nerves." He pointed out that of the 12 proteins found to activate pain-sensitive nerves, only one is a peptide linked to the calcitonin gene-related peptide (CGRP), which is currently a target for migraine treatments. Medications that inhibit CGRP function relieve migraine symptoms in about half of patients, but millions remain without effective treatment.

Rasmussen expressed optimism that the additional molecules revealed in the study could provide new therapeutic options, believing that when patients do not respond well to currently available treatments, it is because the specific molecule responsible for their headache suffering has not been identified. He added that the next step would be to investigate the same processes in humans or animal models more similar to humans.

The researchers' goal is also to closely examine the newly identified pain-stimulating proteins, whether in migraines or other headache disorders, which heralds the potential for developing diagnostic tests and new treatments for a variety of patients.

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