Deleu and Hanssens 5-ht1b/1dagonists in Acute Migraine

A cute migraine is defined as idiopathic, paroxysmal, recurring, moderate-to-severe attacks of unilateral, throbbing headache exacerbated by physical activity and accompanied by associated features such as anorexia, nausea, vomiting, photophobia, and phonophobia. Prevalence rates of migraine vary geographically and range from 1.5% in Southeast Asia to 14% in Western countries. Furthermore, its occurrence is age (most common from ages 25-55 years), race, gender (three times more common in women than in men), and income dependent (affecting lower socioeconomic groups more). Since migraine is a common illness, it imposes an enormous health burden on both patient and society. Work and productivity losses represent 80% to 89% of the economic burden of migraine. While the mechanisms involved in the pathogenesis of migraine are still incompletely understood, it is thought that migraine is a disorder of cranial (pial and dural) blood vessels. Alterations in the activity of 5-hydroxytryptamine (5-HT)-containing neurons in the raphe nuclei and/or norepinephrine-containing pathways originating from the locus coeruleus lead to depolarization of trigeminoperivascular sensory afferents and release of vasoactive neuropeptides (e.g., calcitonin gene-related peptide, neurokinin A, and substance P). This will result in vasodilation of pial and dural arteries (and arteriovenous shunts) and exacerbate nociceptive transmission leading to so-called sterile neurogenic inflammation. Orthodromic conduction transmits this nociceptive impulse to the central nervous system (Figure 1), where it may induce associated symptoms accompanying migraine. Simultaneously, antidromic conduction along the trigeminovascular fibers spreads the depolarization to the neighboring tissues. In addition, reflex activation of intrinsic cholinergic neurons from the facial nerve—which innervates predominantly extracranial blood vessels— amplifies trigeminovascular depolarization and hence the sterile neurogenic inflammation.