What is migraine?
Migraine is a neurological disorder with symptoms that include an intense, throbbing and painful headache, often accompanied by an aura, which is the perception of visual disturbances that appear as flashing lights or zig-zag lines and are usually the first sign that a migraine headache is on its way. A migraine is also associated with extreme sensitivity to light, sound, touch and smell. Other symptoms are gastrointestinal effects including nausea, vomiting and delayed emptying of the stomach into the small intestine, which reduces absorption of medications and can explain why oral medications are not effective fast enough. A migraine attack can last between four and 72 hours.
For many years migraine headache was considered to be a vascular headache and the primary cause was thought to be entirely due to constriction followed by extreme dilatation or widening of blood vessels in the head, with leakage of inflammatory chemicals, which in turn irritate nearby sensory nerves causing pain. With new developments in neuroscience, the current thinking is that migraine headache is a neurological disorder involving abnormalities in nerve pathways and brain chemicals or neurotransmitters. It is also now thought that there are distinct genes related to migraines and that there is a genetic component to developing migraines due to the presence of abnormal genes that control certain areas of the brain.
There are many possible migraine triggers, including, stress, hunger, lack of sleep, dietary factors, and hormonal changes such as during the menstrual cycle.
Medications for treatment of migraine currently focus on the vascular basis of migraine headache to prevent blood vessel widening by targeting two different neurotransmitters, serotonin and noradrenaline. These neurotransmitters act on specific receptors in the brain and control the stability of peripheral blood vessels in terms of dilation and constriction. Other medications are used for control of migraine symptoms by combining an analgesic and antiemetic.
Serotonin is a brain chemical or neurotransmitter that is involved in control of mood, pain sensation, sexual behaviour, sleep, as well as dilation (widening) and constriction (narrowing) of blood vessels. Sumatriptan is a member of the group of drugs called tryptans and is a serotonin agonist that mimics the action of serotonin (also known as 5-hydroxytryptamine, or 5-HT). Sumatriptan acts specifically on the 5-HT1 receptor, which is a sub-type of the serotonin receptor that is found predominantly in the blood vessels of the brain, causing them to constrict or narrow. Sumatriptan is also thought to inhibit trigeminal nerve activity, relieving pain.
Treatment with sumatriptan should begin as soon as possible after symptoms begin and Injection is the fastest treatment for migraine relief, being effective within 10-15 minutes. A nasal spray is also available which delivers sumatriptan directly into the nasal passages where it is rapidly absorbed through the skin and is active within 15 minutes; this is particularly suitable if nausea and vomiting during a migraine attack make it difficult to take tablets. Sumatriptan is not fully absorbed so oral administration with tablets can take up to 30 minutes to relieve symptoms, although rapid release fast disintegration tablets are available to speed up absorption of sumatriptan. Sumatriptan does not prevent migraine attack and is not effective for other types of headache.
Clonidine is an alpha-agonist that acts on alpha adrenergic receptors in the brain and central nervous system, which are usually stimulated by the neurotransmitter noradrenaline. Blood vessels in the brain have alpha adrenergic receptors and are responsive to adrenergic stimulation by the neurotransmitters adrenaline and noradrenaline. This stimulation causes the blood vessels to widen (vasodilation) or contract (vasoconstriction). Clonidine binds to alpha adrenergic receptors on peripheral blood vessels in the brain and this reduces their responsiveness to adrenergic stimuli and thereby controls the extreme dilatation that is thought to be associated with migraine headache.
A combination of the analgesic paracetamol and the anti-emetic metoclopramide is used to help relieve symptoms of migraine, including pain, nausea, vomiting and gastric stasis, or delayed emptying of the stomach, which can slow down the absorption of migraine medication.
Paracetamol works by selectively inhibiting the enzyme cyclooxygenase 2 (COX-2) that is required for the production of prostaglandins, which are chemicals produced in response to inflammation and injury and can also sensitise nerve endings in the pain centres in the brain. Paracetamol blocks the production of pain-inducing prostaglandins, to relieve the pain associated with migraine headaches.
Metoclopramide is an antiemetic (prevents nausea and vomiting) and a gastrokinetic (stimulates gastrointestinal mobility). It acts as a dopamine antagonist by binding to dopamine receptors in specific areas in the brain where the vomiting reflex is stimulated and blocks the vomiting reflex. Metoclopramide also binds to dopamine receptors in the stomach, which mediates increased contraction of the stomach muscles so that the stomach empties faster and this reduces nausea and vomiting and increases the passage of the oral medication into the intestine for faster absorption.