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A New Discovery for Migraine Treatment - TRESK Channels
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The TRESK channels have paved way for the development of potential treatments for migraine.

Migraine is a chronic neurovascular disorder characterized by severe, episodic headaches often accompanied by other symptoms like nausea, phonophobia or sensitivity to sound, photophobia or sensitivity to light, vomiting, etc. A symptom usually precedes the migraine headache, which is a transient, focal, neurological phenomenon, known as aura, which is actually loss of vision or flashes of light. The differences between the causes for the migraine with aura (MA) and the migraine without aura (MO) are not clearly known and some patients experience the symptoms of both the types of migraine.

The exact cause of the migraine was not known until few years back, but successful genetic studies have shown that MA is a genetic disorder and results from some faulty genes, which makes some people predisposed to the migraine condition. The cortical spreading depression (CSD) results in the migraine aura, which is a wave of the depolarization in the pain neurons and the glial cells followed by inactivity and spreads over the entire cortical region. The trigeminal system (TGVS) is activated by the CSD initiating headache. This projects to the brain stem, which in turn projects to the other pain centres in the brain. However, the presence of a link between CSD in MO is not known yet. It has been seen that in some cases migraine like symptoms result due to severe stress or hormonal imbalance, etc, though there is no concrete evidence to prove it.

In case of the genetic disorders, it is often seen that a combination of mutations in several genes result in the disease. However, in the study of Migraine, a genetic disease, it is seen that a defect in a single gene may result in the formation of the disease. MA is also known as Familial hemiplegic migraine. Recent studies have shown that defect in the ion channels and its transporters may be responsible for the formation of the disease. As it is known that ion channels play an important part in the excitability of a nerve, hence a defect in the ion transporters which transport ions in and out of the nerve cells may affect the excitability of the nerve. It is seen that in the migraine sufferers, the excitability of the nerves increases, thereby hinting the presence of fault in the ion channels and its transporters.

While studying the ion transporters and its genes, the latest discovery in relation to the disease has been the identification of a mutation in the TRESK gene in the family of DNA sufferers, by DNA sequencing method. The TRESK gene is responsible for the formation of the protein TWIK related spinal cord potassium channel (TRESK). The TRESK is responsible for the transmission of signals between the nerve cells. It is a potassium channel, which causes the efflux of the potassium ions from the nerve cells. It is mainly associated with the pain pathways because on stimulation, it numbs the pain and prevents the passage of pain signal between the nerve cells. Hence, it plays an important role in the action of the anaesthetics. A mutation in this gene thereby causes increased sensitivity of the nerve cells. Moreover, the TRESK is abundantly present in the trigeminal ganglion region of the brain, which is the major part associated with the transmission of the pain stimuli in the brain. The presence of mutation in this gene was noted in only one large family of migraine sufferers, while the majority of other migraine sufferers showed absence of the same. Hence, it remains to be studied if other less severe defects in the TRESK gene or defects in the genes or proteins associated with it could be a possible mechanism for migraine formation.

The discovery of drugs stimulating the TRESK channel may prove to be an effective treatment, though they may not be potent in case of complete loss of the function of the channel. Moreover, gene therapy for defective TRESK channels may also be a potential ground for research. The ongoing research on the subject may initiate better forms of treatment for the prevalent disease, though extensive, in-depth study is essential for knowing the underlying molecular mechanisms behind the formation of the disease.
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