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CLINICAL RESEARCH AND METHODSPathophysiology of MigraineABSTRACTMigraine is a neurovascular disordercharacterized by a unilateral mild orsevere headache lasting from a fewhours to as long as three days. It hasbeen recently shown in many studiesthat this disorder has a firm andcomplicated genetic background thatexposes individuals to a higher susceptibilityto migraine attacks. Oldtheories used to focus on the vascularchanges and the subsequentblood flow alterations in the brain toexplain the different symptoms occurringduring migraines. New theorieson the other hand are sheddingmore light on the involvement of thenervous system in the brain, primarilythe trigeminal nerve in the brainstem, considering it the primarycause for the initiation of migraineattacks. Changes in blood vessels inthe brain are believed to be an epiphenomenononly.In this article, the pathophysiology ofa migraine attack is explained on thebasis of the unified theory that triesto integrate all the available scientificdata about migraine.M. Bashir Abiad, BS BiologyPathophysiology ofmigraine:Migraine is best defined as achronic disorder of the centralnervous system. It is characterizedby a series of events beginningwith the abnormal over-excitementof certain nerve cells in the brain.These neurons release a pool ofchemicals that stimulate the brain’sblood vessels to swell (vasodilation),and create an inflammatory reactionin the affected area. As a result,the person suffers from a severeand pulsating unilateral headache,accompanied by nausea, vomiting,visual and auditory problems, tinglingof the face and extremities, as well asfatigue, drowsiness and yawning [1] .Migraine attacks may be triggeredby many different factors, includinghormonal changes (observedin menstrual cycles, with oralcontraception or estrogen replacementtherapy, which explains why nearly74% of migraine sufferers in theUnited States are females [2] ). Othertriggers involve dietary factors (likechocolate; alcohol; cheese; yoghurt;fermented, decayed or marinatedmeat and anything that may containtyramine, a monoamine which isproduced by the decarboxylation oftyrosine during fermentation or decayand that causes the release of storedmonoamines (dopamine, epinephrineor norepinephrine) [3] . Changes in sleeppatterns, emotional disturbances(like excitement, fear, anxiety, anger,and stress), allergic reactions, andenvironmental factors (like weatherchanges, bright light, loud noise,certain odors and perfumes) mayalso trigger migraine attacks [4] . Eachperson, with his/her unique geneticbackground, is at a certain thresholdof neuronal excitability in his/herbrain. In fact, specific allele mutationshave been recently discovered to beinvolved in exposing the individualto higher risks to migraine attacks:four different missense mutations inthe α 1Asubunit of the P/Q – type ofvoltage-gated Ca 2+ on chromosome19 affect the release of serotonin,a vasoconstrictor, in midbrain [5][6][7] .ATP1A2 gene, found on chromosome1q23, is also linked to migraineattacks. This gene codes for theα 2subunit of the Na + /K + ATPase [8] .Moreover, the dopamine D2 receptorgene is found to be responsible alsofor increasing the susceptibility tomigraine recurrence [9] .When exposed to the migrainetriggers listed above, the ones withlow threshold (i.e. higher susceptibilityto migraine attacks) will experience ashort wave of neural depolarizationin the brain due to the initial releaseof potassium and glutamate in theoccipital lobe and then propagatethroughout the whole cortex at aspeed ranging between 3 and 6 mm/min. This wave is followed by a longerone of neural depression known ascortical spreading depression, orsimply CSD [1] . These consecutivealterations in the neural activity in thebrain stimulate the vasoconstrictionof specific blood vessels in thebrainstem. If the decrease in the bloodflow goes below a critical value, thedifferent symptoms observed duringthe aura phase (e.g. blurred vision,weakness, tingling or numbness ofthe face and extremities) may beinitiated [10] .It should be noted that one thirdonly of migraine sufferers passthrough the aura symptoms. The resttwo third, despite the electrical wavedisturbances, have what we callmigraine without aura because thedecrease in blood flow in their brainis not so critical [11] . Some studieshave shown that the disruption of thenormal electric status of the brainmight affect the performance of thehypothalamus causing the differentprodromal signs observed severalhours (or even days) before themigraine, like mood disturbances,food cravings, drowsiness, thirst, andyawning [12] .MIDDLE EAST JOURNAL OF FAMILY MEDICINE • VOLUME 6, ISSUE 6 29