Precisely why CSD begins, no one is aware of. Equally, loads of mysteries stay about what prompts the ache of migraines. Previous research have proposed that migraine complications happen when one thing within the cerebrospinal fluid not directly prompts nerves within the close by meninges, the layers of membrane between the mind and the cranium. Rasmussen’s experiment, led by neuroscientist Maiken Nedergaard, initially got down to discover proof to assist this—however they got here away empty-handed. “We didn’t get something,” he says.
In order that they tried a unique strategy, injecting fluorescent tracer substances into the cerebrospinal fluid and imaging the mice’s skulls. The tracers concentrated on the finish of the trigeminal nerve, “these huge nerve bundles that lie like two sausages on the bottom of the cranium.” It was an enormous shock, he says, to search out substances had been capable of attain this a part of the peripheral nervous system, the place they may activate ache receptors. “So we acquired excited and in addition very puzzled—like, how does it even get there?” This led them to the opening—the tip of the trigeminal nerve that was in open contact with the cerebrospinal fluid.
The researchers additionally sampled the cerebrospinal fluid and located greater than 100 proteins that rose or fell within the aftermath of CSD, suggesting potential involvement within the ache of migraine. A dozen of the proteins that elevated are identified to behave as transmitter substances able to activating sensory nerves, together with one known as calcitonin gene-related peptide (CGRP), a identified goal for migraine medicine. Rasmussen says it was a very good signal to search out it among the many combine. “However for us, what’s most fascinating is basically the 11 different proteins that haven’t been described earlier than,” he says—as these might open the door for brand new remedies.
There are nonetheless causes to be cautious, says Turgay Dalkara, a professor of neurology at Hacettepe College in Turkey with an curiosity in auras. Mouse fashions are helpful, however the measurement variations in rodent and human skulls are problematic—particularly in relation to the realm the place the opening was discovered. “From the mouse to the human, the surface-volume ratio is dramatically completely different,” he says. The concept that Rasmussen’s workforce initially investigated—that CSD releases substances that activate and sensitize nerves within the meninges—stays the perfect supported mechanism noticed in people, he provides. Rasmussen’s discovering, of this beforehand undiscovered spot the place cerebrospinal fluid might contact nerves, must be thought-about a potential addition to this image, not a alternative for it.
Hadjikhani agrees however is nonetheless excited to discover a additional pathway for investigation. For docs, the lack of know-how about how migraines work means sleuthing for the suitable combos of medicines to provide victims some aid. “You attempt one. You attempt a mixture. You are taking one off,” she says. “It’s a must to be Sherlock Holmes, discovering what triggers issues.”
The truth that migraines range a lot means there might by no means be a silver bullet answer. Rasmussen hopes that, in the long run, having the ability to observe adjustments in a person’s cerebrospinal fluid might reduce this guesswork and result in personalised options.
