Friday, 5 August 2016

Perspectives in the Therapeutic Treatment of Migraine



Migraine is a disabling disease which affects around 10% of the global population. It is characterized by a strong unilateral and pulsatile headache which is sometimes accompanied by nausea, vomiting, photophobia, phonophobia and other neurological symptoms. During migraine, alterations in the metabolism of serotonin (5-hydroxytryptamine; 5-HT) and in the dynamics of calcitonin gene-related peptide (CGRP) result in vasodilatation of meningeal blood vessels and in facilitation of trigeminal pain integration. The above conditions play a role in the painful phase of migraine. Regarding therapeutic alternatives, classical antimigraine drugs, such as the ergots (e.g. ergotamine and dihydroergotamine), produce cranial vasoconstriction, inhibit trigeminal vasodilatation and inhibit trigeminal pain integration, but some undesirable hypertensive mechanisms induced by systemic vasoconstriction are favoured. These problems led to the development of more selective antimigraine agents like the triptans (serotonin 5 HT1B/1D/1F receptor agonists), which represent the current mainstay of acute antimigraine treatment. However, the triptans: (i) may produce vasoconstriction of coronary blood vessels; (ii) are effective in less than 50% of migraine patients; (iii) are clearly contraindicated in patients with cerebro- and cardiovascular disease; and (iv) do not seem to be useful as prophylactic agents. Hence, more recent antimigraine alternatives include the development of CGRP receptor antagonists (e.g. olcegepant, telcagepant) and human monoclonal antibodies towards CGRP and the CGRP receptor. These antibodies are currently in clinical trials for the treatment of both episodic and chronic migraine with promising results. In short, the inhibition of the CGRPergic system (devoid of triptans-related vasoconstriction) is therapeutically similar to the antimigraine efficacy of the triptans, but hypothetically with fewer side effects. However, chronic blockade of CGRP receptors may represent a potential cardiovascular risk. Meanwhile, the triptans are currently considered the best therapeutic option to abort migraine attacks. The lack of a preventive drug is a persistent necessity for migraine therapeutics.

Migraine is a highly disabling disease characterized by a strong and pulsatile unilateral headache which affects 10% of the world population according with the world health organization. The “Headache Classification Committee of the International Headache Society”  describes several and complex neurological signs and symptoms which may occur before and during migraine. Before migraine attacks, premonitory symptoms such as yawning and scintillating scotoma (aura) may occur. Migraine attacks are sometimes accompanied by allodynia, hyperalgesia, photophobia, phonophobia, anorexia, nausea, vomiting, etc. Pain during migraine is restricted to the head, which suggests the main role of the trigeminal system. All these features dramatically affect the quality of life, not only of the patients, but also of their close family members as well as their social and professional activities.

One interesting aspect of migraine is its higher prevalence in female patients; the ratio is almost 3:1 during the adult life. The origin of this difference seems to be related with hormonal changes in view that the prevalence of migraine: (i) is quite similar in girls and boys under age 10; and (ii) decreases after menopause. On the other hand, there is a correlation between migraine and several psychiatric disorders (e.g., depression) which increase the risk to develop migraine from acute attacks to a chronic problem and consequently to increase the risk for impairing the psychiatric condition. A patient with chronic migraine may develop more than 15 attacks per month, which may represent the potential loss of school, job and/or spouse.

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