Can Ketamine Reduce the Pain of Migraines?
Ketamine is a powerful dissociative anaesthetic that was first synthesized in 1912. Its use as an anaesthetic was not widely used until it became available in the 1970’s. Since then, ketamine has been used extensively for medical purposes such as surgical procedures and anesthesia.
The main mechanism of action of ketamine is the blockade of NMDA receptors. These are ion channels found throughout the brain that control many functions including learning, memory, emotions and movement. When these channels become blocked, they cause severe disruptions in the function of neurons within the affected areas. This causes a wide range of symptoms from mild euphoria to extreme depression or even death.
In humans, ketamine produces its effects through two different mechanisms: direct action and indirect action. Direct actions involve blocking the receptor directly; indirect actions occur when another substance (usually GABA) blocks the effect of ketamine on other receptors.
Direct Actions of Ketamine on NMDA Receptors
1. Binding to the Channel
Ketamine binds to the channel of the receptor itself. When the drug is in place, it prevents other ions such as sodium, potassium and calcium from entering the cell. This blockage of ions causes an increase in electrical activity within the neuron. Due to a build-up of positive charge within the neuron, an action potential occurs which leads to an influx of electrons into the cell. In most cases, this would cause damage to the cell itself.
To prevent this, the cell uses a special type of enzyme called a transporter to pump positive ions back out of the cell. This action allows the neuron to maintain its electrochemical gradient and prevents damage from occurring within the cell.
2. Binding to Enzymes
Another effect of ketamine is to inhibit the actions of enzymes involved in the re-absorption of ions into the cell. This means that even if an ion such as sodium manages to enter the cell, it cannot be re-absorbed back out. This leads to an increase in the concentration of positive ions within the cell which in turn leads to larger action potentials.
Indirect Actions of Ketamine on NMDA Receptors
Ketamine also has several effects that occur indirectly in the brain. These effects are usually mediated through interactions with the neurotransmitter: GABA. There are several types of GABA receptors, but ketamine primarily acts on the GABA-A receptor. When the GABA-A receptor is activated, it leads to an increase in the permeability of the channel. This allows for an influx of positive ions within the cell.
This action reduces the effect of the ion channel within the neuron and temporarily reduces neural activity within that cell. However, this is a bit of a simplification as there are many other effects of ketamine on other types of GABA receptors that have different results. For example, some types of GABA receptors cause an increase in neural activity while others cause a decrease.
How Does This Help With Migraines?
The exact answer is not known, but it is believed that migraines are caused by changes within the neurons in the brain. Since an NMDA receptor is located on these neurons, any changes within this receptor may have a cascading effect and ultimately lead to a migraine headache.
Specifically, the receptors appear to be continually activated for some people. The reasons for this are not fully understood, but it may involve factors such as genetics or an environment toxin. Whatever the cause, the solution is to prevent these receptors from being over-excited.
Ketamine happens to block the NMDA receptors and prevents this continual excitation. The result is a reduction in the symptoms of a migraine, often within minutes. For some people, this can even stop an attack in its tracks. Unlike most drugs used to treat headaches, ketamine also has no notable side-effects when taken at appropriate doses.
Ketamine for Migraine Headaches: The Bad
While there are numerous benefits to using ketamine for migraines, it is not without potential risk. In addition, other drugs may be used to supplement ketamine treatment in some cases. Understanding these limitations and combining with other treatments can help to minimize any risks while reaping the benefits of this treatment option.
The Risks of Ketamine
Currently, the side-effects of ketamine appear to be minimal at prescribed doses. However, it is possible that long-term effects may not be fully known yet or that they will only become apparent after many years of regular use. Even so, the advantages often outweigh any potential risk.
In some cases, a doctor may advise against its use based on certain health conditions or other factors.
Sources & references used in this article:
Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine by H Kaube, J Herzog, T Käufer, M Dichgans, HC Diener – Neurology, 2000 – AAN Enterprises
Intravenous ketamine for subacute treatment of refractory chronic migraine: a case series by C Lauritsen, S Mazuera, RB Lipton… – … of headache and pain, 2016 – Springer
A randomized controlled trial of intranasal ketamine in migraine with prolonged aura by SK Afridi, NJ Giffin, H Kaube, PJ Goadsby – Neurology, 2013 – AAN Enterprises