The precise purpose why CSD was activated is unknown. Likewise, there are nonetheless many mysteries surrounding migraine triggers. Previous analysis has proven that migraines happen when sure substances within the cerebrospinal fluid not directly activate nerves within the close by meninges (the membrane between the mind and cranium). Rasmussen’s experiments, led by neuroscientist Maiken Nedergaard, initially sought proof to assist this concept, however they got here up empty-handed. “We obtained nothing,” he mentioned.
In order that they tried a special method, injecting fluorescent monitoring substances into the cerebrospinal fluid and imaging the skulls of mice. The tracer was concentrated on the ends of the trigeminal nerve, “these large nerve bundles that sit like two sausages on the base of the cranium.” He mentioned it was a giant shock to search out one thing that might attain this a part of the peripheral nervous system and activate ache receptors. “So we have been excited and confused – like, how does it get there?” This led them to the opening – the top of the trigeminal nerve that’s in open contact with the cerebrospinal fluid.
The researchers additionally sampled cerebrospinal fluid and located that greater than 100 proteins have been elevated or decreased after CSD, suggesting a doable hyperlink to migraines. Greater than a dozen of the elevated proteins are identified to behave as transmitter substances able to activating sensory nerves, together with one known as calcitonin gene-related peptide (CGRP), which is a identified goal of migraine medication. Discovering it amongst them is an efficient signal, Rasmussen mentioned. “However for us, probably the most fascinating ones are literally 11 different proteins that haven’t been described earlier than,” he mentioned, as a result of these proteins could open the door to new therapies.
Turgay Dalkara, a professor of neurology at Hacettepe College in Turkey who’s fascinated by auras, mentioned there are nonetheless causes to be cautious. Mouse fashions are helpful, however the dimension distinction between rodent and human skulls is problematic, particularly in the case of discovering areas of openings. “From mice to people, the ratio of floor space to quantity is totally totally different,” he mentioned. He added that the concept initially studied by Rasmussen’s group—that CSD releases substances that activate and sensitize meningeal nerves—stays the best-supported mechanism noticed in people. Rasmussen’s discovery of this beforehand undiscovered place the place cerebrospinal fluid can contact nerves needs to be thought of a doable addition to this image fairly than a alternative for it.
Hajihani agreed, however was happy to search out additional avenues for investigation. For docs, a lack of expertise of how migraines happen means discovering the precise mixture of medicines to offer sufferers some reduction. “You attempt one. You attempt a mixture. You are taking one off,” she mentioned. “You must turn into Sherlock Holmes and determine what triggers the occasion.”
The truth that migraines fluctuate a lot means there could by no means be a magic bullet resolution. Rasmussen hopes that, in the long run, having the ability to observe modifications in particular person cerebrospinal fluid will decrease this guesswork and result in personalised options.