Migraine Research Paper

The headache of migraine results from neurogenic inflammation of first-division trigeminal sensory neurons that innervate the large vessels and meninges of the brain. This causes a change in the way that pain is processed by the brain. Increased neuronal activity can be demonstrated in areas of the brainstem during migraine, and this persists even when the headache is relieved by triptans. It is not known whether this brainstem activation reflects the cause of migraine (the so-called brainstem generator) or instead signifies activation of endogenous pain-control systems.
When activated, the trigeminal neurons release substances that cause dilation of meningeal blood vessels, leakage of plasma proteins into surrounding tissue, and platelet activation. This sensitises nerve fibres so that previously ignored stimuli, such as the normal pulsations of meningeal vessels, are interpreted as painful (peripheral sensitisation). This probably accounts for the pulsating, throbbing character of migraine pain. If the headache continues, second- and third-order neurons are sensitised (central sensitisation) and cutaneous stimuli, such as light touch, are interpreted as painful.
A wave of neuronal excitation spreads anteriorly in the cortex, at a rate of 3 to 5 mm/minute (which correlates temporally with the reported rate of change in visual symptoms). This is followed by a prolonged period of decreased neuronal activity, and finally neuronal recovery. Cortical depression causes release of excitatory amino acids and other mediators of excitation, resulting in activation of nociceptors in adjacent dura and blood vessels, resulting in activation of the trigeminal sensory nucleus. How these neurons are triggered in migraine without aura also is unknown, but one hypothesis is that cortical spreading depression in migraine without aura occurs in 'silent' areas of the brain that do not produce recognisable symptoms of