Now, University of Otago biomedical sciences researcher Prof Debbie Hay and her team are unravelling its complex molecular secrets, hopefully paving a way for new treatments.
Those who live with migraines experience frequent, excruciating attacks that disrupt life for days, and their prevalence is significantly higher among women than men.
Despite decades of scientific research and advocacy efforts, the neurological disorder remains one of New Zealand’s most under-recognised health burdens.
A recent survey of 500 sufferers, led by the University of Otago and the Migraine Foundation Aotearoa New Zealand, found nearly a quarter of respondents lived with chronic migraine (15 or more headache days per month), while one in 10 endured near-continuous pain.
She said the condition often ran in families, indicating clear genetic factors, but it was not linked to a single gene.
Instead, it was a complex genetic makeup which predisposed some individuals in families to attacks.
It was also not simply about head pain, she said.
Migraines involved a much broader spectrum of neurological dysfunction that could unfold over several days.
‘‘Before the painful headache phase, sufferers often experience what’s known as the prodrome, which occurs when parts of the brain, like the hypothalamus, activate and trigger symptoms such as food cravings or heightened sensitivity to light or sound.
‘‘Following the intense headache phase is the postdrome.
‘‘This is otherwise known as the migraine hangover, where the attack resolves but sufferers will be left feeling very drained.’’
Understanding these phases, and the different brain regions involved, was key to developing more targeted treatments, she said.
Medications that blocked the calcitonin gene-related peptide (CGRP) pathway had proven life-changing for patients, but more research about the CGRP was needed, because not all patients responded to these treatments.
And for those who did, the effectiveness could fade over time.
The researchers had been investigating the different drugs on the market, trying to understand their pharmacology.
She said that led them to a second CGRP receptor, known as AMY1, which might also play a role in migraines.
‘‘These insights have only added a new layer of complexity, as these particular migraine-related receptors aren’t single, simple structures, but combinations of different proteins that form in a range of ways.
‘‘Finding tools to study them - whether through identifying tell-tale antibodies or using genetic approaches that switch off individual proteins - is equally tricky.’’
She said one of the biggest remaining mysteries was how some CGRP drugs were unable to cross the blood-brain barrier, but could still effectively treat a neurological condition rooted in brain activity.
‘‘Solving that problem could open the door to new ways of treating migraine without directly accessing the brain.’’
