Trigeminovascular system · Grey Matter

The trigeminovascular system is the set of pain fibres of the trigeminal nerve that supply the meninges and their blood vessels, together with the brainstem neurons they feed, and it is the pathway that turns a migraine attack into head pain.

Trigeminovascular system. The trigeminovascular system is the set of pain fibres of the trigeminal nerve that supply the meninges and their blood vessels, together with the brainstem neurons they feed, and it is the pathway that turns a migraine attack into head pain.

The brain itself has no pain receptors. The coverings around it do: the dura and its large vessels are innervated by thin sensory fibres whose cell bodies sit in the trigeminal ganglion, most of them from the first, ophthalmic (V1) division. When these fibres are activated, they release peptides from their endings, above all CGRP (calcitonin gene-related peptide), which widens vessels and sensitises the tissue. The signal enters the brainstem in the trigeminal nucleus caudalis and the top of the cervical spinal cord, called together the trigeminocervical complex, and is relayed through the thalamus to the cortex, where it is felt as throbbing pain.

CGRP is the best-validated target in migraine. Its levels rise during attacks, giving it to susceptible people provokes migraine-like headaches, and antibodies against CGRP or its receptor (erenumab was the first, approved in the United States in 2018) prevent attacks in many people, with and without aura.

The geography explains where it hurts. Because V1 supplies the forehead and the area around the eye, migraine pain often sits there; and because neurons of the trigeminocervical complex also receive input from the upper neck through the greater occipital nerve (C2), pain spreads to the back of the head and neck.

What sets the fibres off is still studied. In animals, cortical spreading depression releases potassium, glutamate and other substances that reach meningeal fibres and activate them, a plausible start for attacks with aura; for the majority of attacks, which have no aura, changes in the hypothalamus and brainstem before the pain are the other main lead.

Sensitisation explains the extras. Once second-order neurons are sensitised, ordinary touch of the scalp can hurt, and movement makes the pain worse.

Migraine pain is real nociception from the coverings of the brain.

The cortex can start an attack, but the pain travels on the same nerve that carries pain from the face.

Questions: Why does blocking CGRP prevent migraine attacks? CGRP is the main peptide released by activated trigeminal pain fibres in the meninges, where it widens blood vessels and sensitises the tissue and the nerve pathway that carries the pain. Its levels rise during attacks, and giving it to people with migraine provokes migraine-like headaches, which identified it as a cause along the pain pathway. Antibodies that bind CGRP or its receptor (the first, erenumab, was approved in the United States in 2018) and small-molecule receptor blockers interrupt that step, reducing attacks with and without aura, because the trigeminovascular pathway is common to both.