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 method, 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 seek 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 top 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 referred to as calcitonin gene-related peptide (CGRP), a identified goal for migraine medication. Rasmussen says it was an excellent signal to seek out it among the many combine. “However for us, what’s most fascinating is actually 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 with regards to the realm the place the opening was discovered. “From the mouse to the human, the surface-volume ratio is dramatically totally different,” he says. The concept that Rasmussen’s staff initially investigated—that CSD releases substances that activate and sensitize nerves within the meninges—stays one of the best 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 of a attainable addition to this image, not a alternative for it.
Hadjikhani agrees however is however excited to discover a additional pathway for investigation. For medical doctors, the lack of knowledge about how migraines work means sleuthing for the suitable mixtures of medicines to present victims some aid. “You attempt one. You attempt a mix. You’re taking one off,” she says. “You must be Sherlock Holmes, discovering what triggers issues.”
The truth that migraines fluctuate a lot means there could by no means be a silver bullet answer. Rasmussen hopes that, in the long run, with the ability to observe adjustments in a person’s cerebrospinal fluid might reduce this guesswork and result in personalised options.
