Pain in migraine seems to arise from a sort of collision in a sense between some abnormal events within the brain and the brainstem which run down towards the trigeminal complex and coupled with abnormal activity in the trigeminal sensory nerves innervating the vasculature and the dura and the meninges.
The cortex appears to be key to the events that proceed and then culminate in a migraine attack because it’s long been known that as series of abnormal impulses, so called spreading depression, run from the cortex across the brain and this seems to be a key early event in a migraine attack
The limbic areas of the brain are hugely important for our emotional response to pain the fact that it’s an aversive, unpleasant response, it causes anxiety, and we know that in addition to the sensory pathways of pain, which enable us to describe our pain, where it is, the limbic areas are disrupted by painful influences and this likely leads on to the comorbidities that are so common in patients with headaches and other pains.
The brainstem exerts a very important control on inputs into the trigeminal nucleus and it was long thought that the brainstem simply inhibited pain but we now know that there are excitatory pathways as well and during a whole number of pains, not just headaches, it appears that the balance between inhibition and excitation goes wrong.
So in migraines the importance of the periphery just cannot be underestimated. We know that there is very abnormal activity in the sensory endings that are innervating blood vessels, there’s abnormal vasodilation and among a series of culprits we know that this peptide CGRP is enormously important and we can measure release of this during migraine attacks and it can be produced by triggers of migraine as well
The presence of vasodilation in the meninges appears to be an absolutely crucial event. We know that its due to the release of a number of chemicals but probably most important one is CGRP. And this abnormal vascular response in the meninges then appears to drive painful afferents. They terminate in the brainstem and trigger the painful attack.
The triggers for migraine are very, very variable. Some of them are just simply things like fatigue, for example, abnormal light. But of course then can be triggers, there are chemicals, the nitrates, can trigger migraine attacks as well. So it appears that some of these may be acting at peripheral levels but clearly this central abnormalities during migraine attacks, that triggers can alter those events as well.
So I think one of the big unknowns is that we know that there are these peripheral vasodilatations, peripheral nerves being activated, yet all these central nervous system, these brain changes, and I think the key question, which we still don’t fully understand, is how possibly the brain is able to influence these peripheral nerves because it appears that we need both those events and we’re used to the idea that peripheral nerves influence the brain, that’s very well explained, but the vice versa of that, can the brain alter peripheral nerve activity, is still a big interesting question.