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Many neurological diseases remain somewhat of a mystery to researchers — not least headache disorders. This was what led Rune Häckert Christensen to choose neurology as his field when, as a medical student, he had to pick an area of research to delve into.

“I was drawn to headache disorders because there are still many unanswered questions and a large unmet need for treatment. In other specialties, many connections are already well understood and systematized,” says Rune Häckert Christensen, who has received the Lundbeck Foundation Talent Prize for his research on migraine and post-traumatic headache.

His research interest led him to contact the Danish Headache Center at Rigshospitalet. This became the start of a collaboration that developed into both his master’s thesis and PhD project, focusing on MRI scans of headache patients.

The fingerprint of migraine in the brain

Scientific MRI studies are usually based on a small number of patients. But in Rune Häckert Christensen’s case, he and his team performed about 1,000 MRI scans during his PhD — both on patients with migraine, post-traumatic headache, and healthy people. The studies included roughly three times as many participants as comparable MRI studies.

One of the key findings of Rune Häckert Christensen’s research was that migraine is linked to changes specifically in the parts of the brain that process pain. This differed from many earlier studies, which, due to fewer participants, found more scattered changes.

“Our results provide convincing evidence that people with migraine show changes in the brain’s pain-processing regions. For example, we saw that during migraine attacks, certain pain-processing areas reacted more strongly to light and visual stimulation. This helps explain why people with migraine become hypersensitive to light during an attack and seek rest in a dark room,” says Rune Häckert Christensen.

The link between aura and headache
His research investigated two types of migraine — with and without aura. People with aura typically experience temporary visual disturbances before their headache begins — a kind of warning signal.

“In patients with aura, our scans showed signs of inflammation in the visual cortex at the back of the brain — exactly the area responsible for vision and aura symptoms,” says Rune Häckert Christensen.

“For decades, animal models have suggested that the aura triggers an inflammatory state that subsequently leads to migraine. The inflammation thus acts as a kind of link — but it has been very difficult to demonstrate in humans. Our findings are among the very first and most robust evidence that this actually occurs in people with migraine with aura.”

Migraine may start outside the brain

To gain a deeper understanding of the mechanisms that trigger migraine and headache, Rune Häckert Christensen went to Harvard Medical School in Boston, USA, where he worked as a postdoc conducting highly specialized neurosurgical animal studies on rats.

Just like humans, rats have specific pain-sensitive nerve fibres that signal when something hurts. Studying the exact nerve fibres responsible for migraine and headache is extremely difficult and performed in only a few places worldwide — including Boston. There, Rune Häckert Christensen was able to measure the activity directly in the pain-sensitive fibres that send pain signals to the brain.

The aim was to investigate how certain signaling molecules can trigger migraine attacks — and whether this happens inside or outside the brain. One particular molecule, PACAP, known to trigger migraine, was of special interest:

“During our studies in Boston, we found that PACAP activates pain-sensitive fibres outside the brain, which are believed to trigger migraine. This explains how PACAP initiates a migraine attack,” says Rune Häckert Christensen, continuing:

“This suggests that we can stop migraine attacks by blocking PACAP signaling already outside the brain — thereby avoiding the cognitive side effects associated with drugs that penetrate brain tissue. The hope is that PACAP blockade could become a new treatment similar to CGRP antibodies, which are currently among our best therapies — though unfortunately, only about half of patients experience good effects.”

Additional research is needed

Rune Häckert Christensen’s research has primarily focused on mapping the basic mechanisms underlying headache disorders. But he hopes his work will eventually lead to new and effective treatments.

He is now specialising — the first step toward becoming a neurologist — while continuing to pursue research alongside his clinical work.

“My plan is to become a consultant neurologist. Research and clinical work complement each other, and I intend to combine them in the future. Whenever we encounter a patient for whom no further treatment is available, it is a sign that research has not yet advanced far enough,” says Rune Häckert Christensen.

“That’s why I’m very grateful to have received the Lundbeck Foundation Talent Prize. It’s an important recognition that allows me to continue this vital work,” he adds.