Migraine
Introduction
Migraine is a very common disorder that is classified as a neurovascular disorder, meaning that is has both Vascular and Neurological components. It affects approximately 10% of the UK Population and can be debilitating to its sufferers. [23]
Migraine has a series of identifying symptoms, both from the vascular and neurological components of the condition, however the causes of migraine are not yet fully understood. The onset of a migraine is prevalently accompanied by a visual disturbance, known as an Aura. The Aura causes an area of the visual field to be lost and also results in a surrounding ‘shimmer’ effect in the remaining visual field, resulting in visualising of flashing and light zigzags in the visual field. Following these phenomena the onset of the other symptoms occurs, usually after about 30 minutes. Symptoms can include, but are certainly not limited to, severe throbbing headache (which starts unilaterally), an aversion to light (photophobia) and sound (phonophobia), nausea & vomiting and prostration (weakness). [8, 23, 51]
The mechanisms by which migraine occurs are not adequately understood. The onset of migraine may either be due to humoral causes, leading to vascular responses, or neurological disturbance in the brain meninges (protective membrane). The classical view implicates a humorally mediated vasoconstriction intracerebrally. This vasoconstriction is thought to cause the aura / visual disturbances. The headache was proposed to be caused by a following extracerebral vasodilation phase. This proposed model, however, is not supported by more modern studies.
Research has confirmed a biphasic change in cerebral blood flow, with a significant reduction immediately preceding the aura onset; the headache, however, does not coincide with the vasodilation phase but the initial vasoconstriction phase. The headache is also initially localised at the rear of the brain and spreading with time, suggesting a neurological cause. The cause of headache is thought to be due to stimulation of sensory nerves (nociceptive) in the extracerebral structures, such as the meninges or large arteries.
A second hypothesis implicates an underlying neuronal abnormality, spreading in a similar fashion to cortical spreading depression. Thirdly a more recent hypothesis has suggested that the migraine may be caused by activity in peptidergic nerve terminals in the meninges, leading to pain and reinforcement through inflammation processes. This hypothesis rests on the involvement of neuropeptides in the process of inflammation and sensitisation. There is strong evidence that CGRP (Calcitonin-Gene Related Peptide) is heavily involved but other neuropeptides are less certainly involved, although, more recently, Substance P has been verified as a possible involved factor. [16, 18, 45]
Despite the various hypotheses there is not an explanation of the vasoconstriction associated with the aura and other blood flow changes relating to the various key symptoms of migraine. It is likely to involve factors from a variety of proposals. [39, 44]
The evidence linking 5-HT (Serotonin / 5-Hydroxytryptamine) to the migraine process is strong: levels of 5-HT significantly alter throughout a migraine attack and many of the effective treatments are drugs that activate or block (agonists or antagonists respectively) the 5-HT receptor. Release of 5-HT is known to produce an inflammatory response, and hence may support the third hypothesis highlighted. Mediators produced by 5-HT include bradykinin and prostaglandins, which act on nerve terminals to cause pain, inflammation and sensitisation. [2, 6, 8, 41, 51]
