Migraine Physiopathology
Migraine can be viewed as the interaction of environmental triggers and a susceptible brain.
Migraine is an abnormal state of the brain but it was once thought to be primarily a disorder of blood vessels. Vascular changes occur, but they are not primary, and while some now prefer to call migraine a neurovascular disorder, there is ample evidence that patients with migraines have an abnormal central nervous system, resulting in various well-recognized clinical symptoms.
Migraine triggers include physical activity, dietary factors, sleep disturbances, head trauma, hormonal influences, and medications.
Several medical conditions have been shown to be comorbid with migraine (they occur with migraine more frequently than in the general population). These conditions include mitral valve prolapse, patent foramen ovale (migraine with aura), Raynaud phenomenon, stroke, epilepsy, depression, anxiety, bipolar disorder, and social phobias.
Migraine is generally hereditary with polygenic inheritance. Trauma can also precipitate headache with migrainous features, and the pathophysiologic consequences of head trauma have many similarities to migraine.
The understanding of migraine pathophysiology has advanced significantly in the past 20 years.
There is compelling evidence that diencephalic and brainstem nuclei can modulate activation of the trigeminovascular system. The trigeminovascular system consists of efferent projections to the craniovascular structures of the dura mater and cranial blood vessels, and afferent projections from these structures back to the trigeminal nucleus caudalis (TNC) that runs from the medulla down into the region of the third cervical segment where it blends gradually into the cervical dorsal horns.
Fibers from upper cervical roots enter the TNC, which sends fibers rostrally to the thalamus and collaterals to the autonomic nuclei in the brainstem and the hypothalamus. Thalamic neurons project to the somatosensory cortex but also to areas of the limbic system.
Pain from the face and head may be referred to the neck, and pain from the neck can be referred to the face, especially in the distribution of the first division of the trigeminal nerve (V1). The greater occipital nerve (formed by C2), is often tender during an attack of migraine or cluster headaches and an occipital nerve blockade can terminate an attack.
Cortical Spread Depression (CSD) may also play an important role in the genesis of a migraine attack.
CSD is a wave of neuronal depolarization followed by a suppression of neuronal activity with blood flow changes that starts at the occipital lobe and moves across the cerebral cortex at rate of about 3 mm/min. Meningeal nociceptors are activated, mast cells are activated and degranulate. The trigeminovascular reflex is activated. Trigeminal neurons supplying the dural vessels release calcitonin gene-related peptide (CGRP), substance P, and neurokinin A.
The vessels dilate and become inflamed, and plasma protein extravasation occurs (also known as sterile neurogenic inflammation) in addition to central sensitization, and is perceived as head pain.
Increased CGRP is found in the jugular veins of patients with migraines during an attack.
