Introduction

A migraine is a debilitating and recurrent type of headache characterised by moderate to severe pain on one side of the head.¹ Not only does a migraine cause a headache, but it also is related to a range of other symptoms affecting the whole body. 

Common symptoms of a migraine:

• Headache
• Sensitivity to light, sounds and smells
• Nausea
• Vomiting
• Flashing lights in vision

Commonly, a person may get warning signs before the migraine, this is called a migraine with an aura. Symptoms associated with an aura include:

• Vision problems
• Numbness and tingling that feels like pins and needles
• Dizziness
• Difficulty speaking

A migraine can last anywhere between 3 hours and 3 days. Different people experience different levels of severity and duration. The symptoms of a migraine can affect one’s ability to carry out everyday activities. 

In the UK, approximately 10 million of the adult population suffer from migraine attacks culminating in a combined loss of around 3 million workdays annually. The high prevalence of migraines and their effect on everyday life highlights the necessity for effective acute migraine relief. 

The triptans are a class of medication used in the treatment of an acute migraine attack. They bind to the 5-HT1 receptors (serotonin receptors) and elicit a response, therefore they are known as 5-HT1 receptor agonists.³ The triptans possess several mechanisms of action associated with the relief of a migraine. Here, we will discuss these mechanisms of action further. 

Overview of migraine pathophysiology

Neurovascular theory

The term ‘neurovascular’ refers to the blood supply and blood vessels within the brain and spinal cord. In the 1900’s, Wolff proposed the neurovascular theory of migraine commencing with the vasoconstriction of the cranial vasculature.⁴ Following the vasoconstrictive phase, the meningeal vessels dilate resulting in the activation of the trigeminal nerves surrounding them.⁴ The activation of these nerves causes pain. 

The role of serotonin in migraine pathophysiology 

Serotonin (5-HT) is a neurotransmitter involved in the vasoconstriction of nerve endings and blood vessels. Studies have indicated that low levels of 5-HT can lead to vasodilation and thus initiate a migraine.⁵ 

Many migraine sufferers have reported that the migraine eases off after vomiting.⁵ A surge in the levels of 5-HT in the blood is associated with nausea and vomiting.

As well as their vasoconstrictive properties, 5-HT receptor agonists reduce trigeminal nerve activation, reduce pain and inhibit the CGRP cascade.⁶ The CGRP cascade involves the exacerbation of vasodilation and increased pain.

Trigeminal nerve involvement

The trigeminal nerve is the 5th cranial nerve and also the largest. It consists of 3 divisions: mandibular, maxillary and ophthalmic divisions. Primarily, it functions to provide sensory innervation to the face. In migraine, the activation of these nerves is responsible for the headache. 

The trigeminal nerve terminals are the site of the release of neuropeptides, including CGRP, which result in further vasodilation and worsening pain.⁷ Therefore, targeting the trigeminal nerve terminal may prove necessary whilst developing acute migraine relief.

Mechanism of action of triptans

Currently, triptans are the gold-standard treatment for acute migraine relief. They are a 5-HT receptor agonist. The discovery of the presence of 5-HT receptors on the human trigeminal ganglion was an indication that this receptor may play a role in treating migraines. 

The triptans relieve migraines, within 2 hours, in approximately 42-76% of patients. They are more effective than NSAIDs, acetaminophen and ergot medication in the treatment of migraine. 

The triptans possess different modes of action which all contribute to their antimigraine effects.⁸ These include:⁸ 

• Vasoconstriction of cranial blood vessels
• Inhibition of nociceptive neurotransmitter release
• Inhibition of the release of vasoactive neuropeptides

Vasoconstriction of neurovasculature

Significant populations of the 5-HT_1b receptor have been located on neurovascular smooth muscle cells.⁸ The agonism of these receptors is responsible for the contraction of the smooth muscle cells and consequently the vasoconstriction of the blood vessel. The triptans activate the 5-HT receptors on the smooth muscle cells which leads to the vasoconstriction of the cranial blood vessels that had dilated during a migraine. 

Inhibition of nociceptive neurotransmitter release

In migraine, the dilation of cranial blood vessels evokes a painful response from the trigeminal nerve. The agonism of the 5-HT receptors, with triptans, inhibits the firing of the trigeminal nerve terminals thus inhibiting the release of the nociceptive neurotransmitters.⁸

Inhibition of the release of vasoactive neuropeptides

CGRP is a powerful vasodilator which is released by the trigeminal nerve terminals when they are activated.⁹ Studies on rats showed that rizatriptan blocked electrically stimulated vasodilation via the inhibition of CGRP release from the trigeminal nerve terminals.⁸ Further studies also demonstrated the dose-dependent relationship of sumatriptan on the inhibition of the release of CGRP from trigeminal nerve terminals.⁸ These studies indicate the triptan's ability to block a positive feedback loop which ultimately leads to sustained vasodilation and pain.

Pharmacokinetics of the triptans

There are several different drugs within the triptan family, including sumatriptan, zolmitriptan and frovatriptan. The absorption of sumatriptan from the gut is rapid but unreliable whereas other triptans have shown more reliable absorption.¹⁰ Usually, an adequate blood concentration of triptans is reached within 30-60 minutes of administration. 

The triptans can be administered via injection, nasal spray, oral tablet or orally disintegrating tablets. These alternative routes enable drug absorption when an oral tablet is not viable due to nausea and vomiting accompanying the migraine. 

Both hepatic metabolism and renal excretion aid in the elimination of the triptans.¹¹ The average half-life is 2-6 hours. 

Side effects of triptan medication

Most medicines have side effects. The triptans are no exception. Although many people don’t experience side effects, some do. Some of the side effects include:

• Nausea and vomiting
• Dizziness
• Drowsiness and fatigue
• Flushing
• Nosebleeds after the nasal spray
• Bruising and tenderness at the site of injection 
• Angina due to coronary artery vasoconstriction. (There are 5-HT_1b receptors present in the coronary artery)
• Tightness, tingling, heaviness or pressure sensation in the face, arms, chest and legs
• Unusual sensation of warmth in the head, neck, chest and limbs

FAQs

What is a migraine?

A migraine is a moderate to severe throbbing headache usually localised to one side of the head. 

What can trigger a migraine?

There are a lot of different factors that can trigger migraine, including hormonal changes, stress, tiredness, too much caffeine, not eating enough and not exercising enough. 

How long will my migraine last?

Usually, a migraine lasts between 3-72 hours. If it lasts longer, seek medical help. Following a migraine you may take a few days to feel ‘normal’ again. 

What causes a migraine? 

The dilation of the blood vessels supplying the brain and spinal cord leads to a cascade of events that encourages further dilation. This dilation is the cause of migraine pain. 

What are the triptans?

The triptans are a family of medications used in acute migraine relief. They cause vasoconstriction of the distended blood vessels. 

Can I buy the triptans in my local pharmacy?

You must seek a prescription from your GP first.

Summary

There is a high prevalence of migraine sufferers in the population. Migraines cause moderate to severe pain that can disrupt the daily activities of a person. Triptans are the current gold standard for acute migraine relief. They are not a preventative measure but aim to ease the pain once a migraine has started. The triptans are a 5-HT receptor agonist and ultimately lead to the vasoconstriction of neurovasculature that has painfully dilated in a migraine. 

The mechanism of action of the triptans include: vasoconstriction, inhibition of the release of vasoactive neuropeptides, inhibition of nociceptive neurotransmitters, anti-inflammatory effects and disruption of NO pathways. 

Unfortunately, the triptans are not 100% effective for everyone. However, the majority of people respond well to this form of acute migraine relief.