How does the brain cause headaches if it can't feel pain?
Do you suffer from migraines? We might have some new clues about how they happen.
If you’re a migraine sufferer like me, you know the classic symptoms.
First, something just feels off, then you see blurry lightning bolts followed by a nasty headache that can last for hours (or days!)
Migraines aren’t fun and humans have suffered from them for basically our entire existence.
The earliest descriptions of them can be found in writings from ancient Egypt and the word migraine comes from Greek and means ‘pain in half of the head.’
We’ve come a long way in 3500 years, but still struggle to understand how migraines work.
60% of people suffer from prodrome (sensitivity to light, sound, etc), most people experience the aura phase (visual aberrations or odd sensory feelings), and almost everyone has the pain or headache phase.
Studies of the brains of migraine sufferers have shown that the brain undergoes Cortical Spreading Depression (CSD) at the onset of migraine symptoms.
This is just a fancy way to say that the brain experiences a period of hyperactivity followed by a wave of inhibition and it’s CSD that is most likely responsible for the weird feelings that are experienced during the aura phase.
But the pain phase of migraine is interesting because the brain itself doesn’t have pain receptors.
So, how does the brain tell the rest of the body there’s a problem if it can’t feel pain?
It seems to do this by signaling that pain through the peripheral nervous system and the nerves in our face, jaw and neck.
The authors of today’s paper show how that happens.
They discovered in mice that the central nervous system can signal to the PNS through cerebrospinal fluid.
They figured this out by staining CSF and watching through a microscope as the fluid flowed from the CNS to the trigeminal ganglion (the nerve bundle that transmits signals from the jaw and face).
This in itself is a huge development because signals from the CNS and PNS usually travel through the nerves, but since the brain doesn’t have pain receptors, that can’t happen!
So, evolution found a way.
The authors then went on to sample the CSF to see what changed in it to signal this headache inducing pain response from the brain via the trigeminal ganglion.
What they found can be seen in the figure above: A) plot showing gene expression changes. B) Analysis showing how stuff in the CSF can signal to the cells of the trigeminal ganglion. C and D) Microscopic view of migraine CSF stimulating the ganglion more than an artificial control (aCSF). E, F, and G) Quantify stimulation and show that old CSF doesn’t have the same effect.
This work is important because it shows a novel mechanism for how the brain can trigger ‘headaches’ during migraine and offers new pathways to target for therapeutic development.
Brian Krueger