Migraine headache is an episodic headache disorder. It is a common condition with a prevalence of 17.6% in females and 5.7% in males. An American Migraine Study estimated that 23 million persons older than 12 years of age have severe migraine headaches; however, this condition is under-treated and under-diagnosed worldwide. Not all headache sufferers seek medical attention, but those who do generally consult family practitioners, internists or pediatricians, ophthalmologists, and neurologists The social and economic effects of migraine are staggering--perhaps $2 to $17.2 billion are lost in productivity per year. The treatment of migraine has not only medical but also serious economic and social implications. Thus, primary-care physicians should be well versed in the diagnosis and treatment of migraine. Rational migraine treatment necessitates an accurate diagnosis, identification and removal of potential triggering factors, non-pharmacological and if needed pharmacological intervention. Both the avoidance of migraine trigger factors and the use of non-pharmacological therapies have a part to play in overall migraine management (1). Effective management also includes establishing realistic expectations, patient reassurance, and education (2).
SYMPTOMS COMPLEXES IN MIGRAINE:
Any attempt to explain the pathophysiology of migraine has to account for the following components of the attack:
The aura may last 20 to 30 minutes and may include one or more of the following:
|•||Mood changes (commonly a sense of elation associated with hyperactivity)|
|•||Increased appetite (particularly for sweet foods).|
|•||Excessive yawning may precede migraine by as long as 24 hours, on at least some occasions, in about one third of migraine patients.|
|•||Blindspots (scotomata) or visual field cuts may have distinctive scintillations or fortification patterns around them. Typically, the scotomata clear as the headache appears.|
|•||Sensory hyperacuity ( light may be perceived as dazzling or may provoke pain, sounds may appear unnaturally loud, and smells may be more intense during (or even before) the headache phase).|
Focal Neurological Symptoms
|•||These neurological symptoms may arise from the cerebral cortex, brain stem, or cerebellum and may anticipate the onset of headache as in the prodromal phase of classic migraine or may appear during the headache phase.|
|•||Focal neurological symptoms of classic migraine, whether arising as a prodrome or developing during the headache phase, are accompanied by diminished cortical perfusion of the appropriate part of the opposite cerebral hemisphere. On some occasions a wave of hypo-perfusion may advance slowly over the cortex in association with a slow march of visual or other neurological symptoms whereas on other occasions it may persist as a local or diffuse cortical oligemia. It is clear that the presence or absence of headache does not depend on changes in cerebral blood flow.|
|•||It is unilateral in two thirds of patients. It commonly starts as a dull ache at the occipito-nuchal junction, or in one temple and then spreads over that side of the head or the whole head or may remain localized as a "bar of pain" extending from the eye to the occiput. The pain is usually constant and unremitting but assumes a pulsatile or throbbing quality when sever, it may consistently affect the same side of the head or may move from side to side, even in the one migraine episode. Pain may radiate down the neck to the shoulder or, in some cases, to the arms and even the leg on the same side of the body, suggesting that the spinothalamic tract has collaborated with trigeminal pathways in the production of pain.|
|•||The frontal branches of the superficial temporal artery become distended in about one third of patients, venous engorgement may be seen, and heat loss increases from the affected area. Most patient appear pale and "dark under the eyes" as the headache worsens, although exceptional patients flush before or during the attack. Sensitivity of the scalp to touch and muscular hyperalgesia may develop during, and outlast, the headache phase.|
|•||However headache of migraine is not necessarily associated with vascular pulsation, dilation of extra-cranial arteries or increased cerebral perfusion.|
|•||Nausea sometimes precedes the onset of headache but commonly evolves as the attack progresses and may culminate in vomiting. Diarrhea is associated in about 20%of patients. Such gastrointestinal symptoms are mediated by an enzyme, dopamine beta-hydroxylase(DBH) that is the final enzyme in the synthesis of noradrenaline.|
|•||PAIN-SENSITIVE CRANIAL STRUCTURE|
|•||The foundation for any study of the causes and treatments of headache is knowledge of the pain-sensitive structures and pain-conducting pathways within the cranium.|
|•||All available evidence supports an orderly somatotopic representation of the supratentorial pain-sensitive meningeal and vascular structures within the trigeminal system. Pain sensation from posterior fossa structures is carried centrally by the vagus nerve, the upper three cervical nerves, and possibly by trigeminal afferents as well.|
THE ORIGIN OF MIGRAINE HEADACHE
The bones of the skull and brain substance are insensitive to pain because they lack pain sensitive nerve fibers.
Pain is referred to the frontotemporal area of the skull, from the following structures:
|•||The intracranial segment of the internal carotid artery.|
|•||The proximal few centimeters of the anterior and middle cerebral arteries.|
|•||A portion of the cerebral veins and venous sinuses.|
|•||The middle meningeal artery.|
|•||The superficial temporal artery.|
The previously mentioned structures contain pain sensitive nerves with the nociceptors at their ends. The latter can be stimulated by stress, muscular tension, dilated blood vessels and other triggers of headache. Once stimulated, the nociceptor sends a message up the length of the nerve fiber to the nerve cells in the brain, signaling that a part of the body hurts. In periarterial fluid sampled during migraine headache, a polypeptide was found, named "neurokinin". This bradykinin-like substance was postulated to set up a sterile inflammatory response in the vessel, which became pain-sensitive, and is responsible for the transmission of the pain impulse to the brain nerve cells.
Platelets aggregation takes place in subgroups of migraine patients and may be a factor in the vascular thrombosis of "complicated migraine". However the blood platelets in most patients seem to be remarkably normal and their role in migraine is probably limited to aggregation in some instances and to serotonin release which potentiats the pain-producing effect of bradykinin.
Dilation of scalp arteries in this area contributes to the intensity of headache, and compression of the temporal artery eases the pain.
Platelet serotonin content increases before migraine attacks and falls during the headache phase in most migraine patients. A serotonin-releasing factor was found present in the blood during migraine headache. The main metabolite of serotonin, 5-hydroxyindoleacetic acid, is excreted in excess in the urine of some patients during migraine attacks. However it seems unlikely that the amount of serotonin released from platelets during migraine headache would be sufficient to cause any vascular constriction, but it may possibly combine with bradykinin to render the arterial walll sensitive to painful dilation. It has been postulated that free fatty acids might be responsible for the release of serotonin from blood platelets in migraine.
Blood histamine is significantly increased after migraine headache. It is claimed that liberated histamine might contribute to the vascular component of migraine.
Prostaglandins, long-chain unsaturated fatty acids derived from arachidonic acid, have potent constrictor and dilator effects. During migraine headache, plasma levels of PGE1 do not alter, but the level of PGE2-like substances has been shown to fall significantly, in contrast with its elevation found in cluster headache.
THE MECHANISMS OF MIGRAINE
Hypotheses for the mechanisms of many aspects of migraine have been extensively studied (3). The aura symptoms are, most likely caused by a mechanism similar to spreading excitation and depression (4).
It is has been believed that migraine attack is a specific reaction pattern to an episode of focal cerebral hypoxia. This hypothesis holds that any type of focal brain hypoxia (and thus not only a vasospasm) may provoke a migraine attack. Indeed, as hypoxia is a result of an imbalance between energy supply and energy use, the former can be decreased and/or the latter be increased. Spreading cortical depression, leading to the aura, is believed to be a consequence of brain hypoxia occurring in classical migraine. There are no genuine differences between classical and common migraine, according to the cerebral hypoxia theory. The latter theory may improve our understanding of the mode of action of antimigraine drugs. Certain calcium entry blockers have a direct protective effect on brain hypoxia, but some other pharmacotherapeutic approaches may also prevent cerebral hypoxia via an effect on brain metabolism, vasomotion or platelet behavior (5). It has been postulated that the classic migraine is both spreading cortical depression and localized ischemia linked in a vicious cycle by potassium induced vasoconstriction. The cycle can be initiated by any event that raises the local cortical ECF (extra-cellular fluid) potassium concentration to approximately 20 mM. Such an event could be a localized burst of activity of a group of cells, localized metabolic impairment, or a transient reduction in blood flow to a region of the cortex. Once this level of potassium concentration is reached, it may result in localized depolarization of neurons, releasing more potassium into the ECF. As the concentration continues to rise, vasoconstriction becomes more intense, perpetuating the cycle that results in localized depression of cortical neuronal activity and ischemia. The condition is propagated to adjacent regions of the cortex by diffusion and glial-mediated spread of potassium (6).
Neuronal hyperexcitability between attacks may be due to:
|•||Abnormality of presynaptic calcium channels.|
Like many others neurological diseases, mitochondrial involvement, by means of abnormalities in cerebral oxidative metabolism, may play a role in migraine(7).
The importance of magnesium in the pathogenesis of migraine headaches is clearly established by a large number of clinical and experimental studies. However, the precise role of various effects of low magnesium levels in the development of migraines remains to be discovered.
Magnesium concentration has an effect on:
|•||Nitric oxide synthesis and release.|
|•||A variety of migraine related receptors and neurotransmitters.|
The available evidence suggests that up to 50% of patients during an acute migraine attack have lowered levels of ionized magnesium. Infusion of magnesium results in a rapid and sustained relief of an acute migraine in such patients. Two double-blind studies suggest that chronic oral magnesium supplementation may also reduce the frequency of migraine headaches (8). Increased tissue levels of taurine, as well as increased extracellular magnesium, could be expected to:
|•||Dampen neuronal hyperexcitation.|
|•||Increase tolerance to focal hypoxia.|
|•||Taurine may also lessen sympathetic outflow.|
Thus it is reasonable to speculate that supplemental magnesium taurate will have preventive value in the treatment of migraine.
THE HUMORAL-VASCULAR THEORY OF MIGRAINE
The humoral-vascular theory postulates that circulating vasoactive amines constrict the cortical microcirculation, thus causing the neuralgic symptoms and signs classic of migraine and that a subsequent phase of dilatation (predominantly extracranial ) is responsible for headache. Dilatation of extracranial, middle meningeal, or cerebral arteries is thought to cause pain in migraine because the vessel wall has been sensitized by the adsorption of serotonin released from platelets and the periarterial accumulation of histamine and bradykinin, causing sterile inflammatory response around extracranial vessels. In case of normal immune system Opioid-containing immune cells migrate preferentially to inflamed sites, where they release beta-endorphin which activates peripheral opioid receptors to inhibit pain. This immune response is altered in migraine patients. Immunocyte recruitment is a multistep, sequential engagement of various adhesion molecules located on immune cells and vascular endothelium. Selectins mediate the initial phase of immunoctye extravasation into inflamed sites. Anti-selectin treatment abolishes peripheral opioid analgesia elicited either endogenously (by stress) or by corticotrophin-releasing factor. This results from a blockade of the infiltration of immunocytes containing beta-endorphin and the consequent decrease of the beta-endorphin content in the inflamed tissue. These findings indicate that the immune system uses mechanisms of cell migration not only to fight pathogens but also to control pain in injured tissue. Thus, pain is exacerbated by measures inhibiting the immigration of opioid-producing cells or, conversely, analgesia might be conveyed by adhesive interactions that recruit those cells to injured tissue (9).
A significant reduction in peripheral blood mononuclear cell beta-endorphin concentrations was observed in migraine patients with and without aura. Altered transmitter modulation to peripheral blood mononuclear cells may be the cause of this alteration, which could be part of a more diffuse opioid system derangement in migraine subjects (10). The life span pattern of circulating peptide, beta-endorphin (B-EP) is characterized by a progressive increase during prepuberal development, by stable levels in adults with typical circadian and monthly variations, and by a decrease in aging subjects. The concomitant changes in the reproductive system suggested the possible influence of gonads on B-EP plasma levels, as confirmed by decreasing B-EP levels in gonadectomized humans and rats. Headache, which is likely to occur concomitantly with hormonal milieu variations, appeared to be associated with a deficiency in the B-EP system, centrally and peripherally, the lowest values being found in the protracted forms of headache (11). The somatostatin-like (SLI), the neuropeptide Y-like (NPY-LI), and the beta-endorphin-like (BE-LI) immunoreactivities of cerebrospinal fluid (CSF) obtained by suboccipital puncture, or plasma from patients suffering from common migraine were analyzed. The SLI concentration was tendentiously decreased in the migraine patients during the attack-free period. During the migraine attack the level of SLI was further decreased. Similar alteration was found in the CSF BE-LI, while the BE-LI in the plasma showed only a tendentious decrease in common migraine patients. The NPY-LI did not change during the attack period in the CSF or plasma. These findings may indicate the possible role of somatostatin in the pathogenesis of common migraine, and support earlier observations that beta-endorphin is involved in the development in this disorder (12). Specific chemical mediator release such as histamine and the prostaglandins (PG2a or PGD2) associated with headaches has been found in a few patients who were repeatedly challenged with specific food (5).
Histamine is able to induce spontaneous-like headache attacks in migraine and cluster headache subjects. Therefore, it has been considered as a possible agent in the pathogenesis of headache. Histamine desensitization is used for the treatment of cluster and other chronic headaches like migraine with interparoxysmal headache (13). A double blind, placebo-controlled trial was performed to establish the duration of action of antihistamines and their ability to attenuate the adverse effects associated with histamine release. It has been found that an adequate dose of antihistamines is recommended to achieve appropriate chemoprophylaxis (14).
Headache can be induced by histamine in wine sensitive patients suffering from histamine intolerance, a disease characterized by impaired histamine degradation based on reduced diamine oxidase activity or a lack of the enzyme. As supportive treatment, a vitamin B6 (pyridoxal phosphate) substitution appears useful in histamine-intolerant patients as pyridoxal phosphate seems to be crucial for diamine oxidase activity. Histamine intolerance, based on reduced diamine oxidase activity or a lack in the enzyme, causative for wine/food-induced chronic headache. According to the localization of diamine oxidase in the jejunal mucosa, histamine intolerance is primarily a disease of intestinal origin. A histamine-free diet is the treatment of choice in histamine-intolerant patients suffering from chronic headache. In addition, it is also important to avoid diamine-oxidase-blocking drugs and alcohol which act as inhibitors of diamine oxidase. As avoidance of histamine-rich food is simple, inexpensive and harmless treatment, histamine-containing food such as cheese and alcoholic beverages should be labeled (15).
Platelets aggregation and the platelet release reaction are caused by a plasma substance of low molecular weight, which could be one or more of the free fatty acids liberated by catecholamines secreted as part of a response to stress. A reported case of acute promyelocytic leukemia and disseminated intravascular coagulation presented with migraine with aura as the first sign may support theories of platelet serotonin involvement in the pathogenesis of migraine (16).
Endothelin-1 (ET-1) exerts powerful vasoconstrictive action. The lower plasma level of ET-1 observed in the patients with migraine is consistent with the pathogenesis of migraine, further supporting the hypothesis that a lower ET-1 may be closely related to marked vasodilatation following the vasoconstriction (17).
THE NEUROGENIC THEORY OF MIGRAINE
This theory postulates that migraine headache involves trigeminovascular and brainstem mechanisms. The ability to trigger an attack may depend on a threshold of brain excitability.
Monoamines have been considered to be the neurotransmitters most likely to be involved in the mechanism of migraine because blood levels of noradrenaline and serotonin fluctuate with the course of headache. The newly acquired knowledge of brain stem monoaminergic nuclei and their influence on cortical activity and cerebral blood flow as well as their participation in the endogenous pain control system makes it feasible to erect a neurogenic hypothesis without completely excluding some aspects of the humoral theory.
Because migraine is a familial disorder, there may well be hereditary anomaly of monoaminergic transmission, that copes well enough under normal circumstances. This mode of transmission is vulnerable to sudden changes in the internal or external environment to emotional stress, or to overload of afferent systems by excessive glare, noise, smells, or other stimuli. All of these factors are known to impinge on the brain stem monoamine nuclei that project diffusely to the cerebral cortex.
If monoaminergic systems were genetically unstable in subjects prone to migraine, trigger factors could induce a phase of excessive neuronal discharge followed by a state of monoamine depletion. Finally, in a state of monoamine depletion, the pain gate would be opened, giving rise to spontaneous pain in the head and neck. The conclusion that central monoamine systems play a central role in the pathophysiology of migraine is difficult to escape.
Thus the physiologic and biochemical observations of patients during migraine attacks led to the accumulation of a lot of data awaiting synthesis. The common ground of the various hypotheses for the mechanism of migraine is the involvement of monoamines, neurotransmitters, centrally, and the humoral agents(serotonin and adrenaline) peripherally. This is supported by pharmacological evidence from the results of treatment. Most effective interval therapy for migraine alters the availability or action of serotonin (methysergide, pizotifen), noradrenaline (beta-blocking agents), or both monoamines (amitriptyline, monoamine oxidase inhibitors). Other agents that act directly on vascular smooth muscle, such as the calcium-entry blocking agents, may diminish vasoconstriction, whether produced by humoral agents or by intrinsic monoamine pathways from brain stem to cortex. Non-steroid anti-inflammatory agents presumably suppress the sterile inflammatory responses in vessel walls.
When is Headache a Warning of a More Serious Condition?
Like other types of pain, headaches can serve as warning signals of more serious disorders.
|•||Migraine is a risk factor for cerebral stroke, particularly in young women. The symptoms and lesions of migrainous stroke suggest the involvement of a mechanism similar to that of migrainous aura, although the infarction process is of greater intensity and lasts longer. Migrainous stroke should be considered an evolutionary complication of aura. Thus, the best treatment consists of adequate control of migraine attacks with the reduction of frequency, intensity and duration. The avoidance of migraine drugs with marked vasoconstrictive action, and the removal of other vascular risk factors (smoking and oral contraceptives) are additional measures for the prevention of migrainous stroke (18).
In addition to vasoconstriction, activation of clotting factors plays a role in the pathophysiologic mechanism of migraine-related stroke. However cerebro- and cardiovascular evaluation is important in patients with suspected migrainous stroke to exclude the diagnosis of paradoxical cardioembolic stroke through a patent foramen ovale (19).
|•||Familial hemiplegic migraine (FHM) is an autosomal dominant condition. Attacks start in childhood, adolescence, or early adulthood. They invariably include a unilateral weakness lasting 30 to 60 minutes and almost always associated with visual, sensory, or speech disturbances. They are occasionally very severe with a dense hemiplegia, confusion, coma or fever, but they always completely recover. Brain neuroimaging is normal. In 20% of the families, migraine is associated with permanent neurological signs, mainly nystagmus and cerebellar ataxia (20).|
|•||Migranous infarction is reported due to severe diffuse intracranial major arterial vasospasm that can be demonstrated by arteriogram. Migranous infarction is represented by recurrent episodes of migraine with aura, that progress to develop a continuous intractable headache during the course of which cortical blindness and quadriparesis occurs due to extensive and bilateral hemispheric cerebral infarction (21).|
|•||Brain hemorrhage: The connection between brain hemorrhage and migraine has been studied. It has been postulated that the brain hemorrhage might be related to vascular lesion brought about by ischemia secondary to vasospasm (22).|
|•||Intracranial vascular malformations (IVM):Migraine is sometimes the presenting feature of patients with intracranial vascular malformations (IVM). A high prevalence of migraine type headaches and a strong positive correlation between the site of AVM and side of the pain was found (23). Migraine could be the only complaint in patients affected by an intrasellar aneurysm (24).|
|•||Migraine and migraine-like headaches are sometimes associated with acquired types of carotid artery stenosis or occlusion (25).|
|•||Occipital lobe tumor can be presented clinically as migraine with typical aura (26).|
|•||Migraine with aura has been reported as the presenting sign of acute promyelocytic leukemia and disseminated intravascular coagulation. This may support theories of platelet serotonin involvement in the pathogenesis of migraine (27).|
Danger signals that should alert the physician to consider a potentially sinister cause:
|•||Sudden onset of a new, severe headache-"the worst headache ever"|
|•||A progressive headache course.|
|•||Onset of headache with exertion|
|•||Onset of headache during or after middle age.|
|•||Headache associated with a decreased level of consciousness.|
|•||Headache associated with meningeal signs.|
|•||Headache associated with abnormal physical signs including fever.|
|•||Failure of headache to "fit" a benign profile.|
|•||Headache in a patient with a systemic malignant disease, infection or immunocompromised state.|
Clinical features that suggest the benign nature of a migraine attack.
|•||Precipitation by menstruation|
|•||Amelioration with sleep.|
|•||Amelioration during pregnancy|
|•||Appearance after sustained exertion.|
|•||Triggers such as alcohol, odors, foods, or changes in the weather.|
Trigger Factors of Migraine
Migraine attacks or other headaches are often triggered (rather than caused) by one or more of the following factors:
|•||Stress is the most frequently cited precipitant in migraine (28). Patients most commonly recognize stress. Migraine brought on by stressful situations and events. The onset of attacks is usually during the period of calm immediately after such moments of stress (29).|
|•||Odontogenic pathogenic factors (dental problem), good diagnostic examination in the field of tooth-, jaw- and mouth medicine should be conducted in every migraine patient, even in "typical" migraine patients. When indicated, operations should be done (30).|
|•||Weather changes e.g. Chinook weather conditions in the Calgary. Older migraine sufferers appear particularly vulnerable to this effect (31).|
|•||Cheese,chocolate, red wine and beer sensitivity: it is believed that these foods and several others contain vasoactive amines, such as tyramine, which constrict arteries, the first step of migraine process. Others believe that foods cause headaches by setting off an allergic reaction in susceptible people. Food-triggered migraine usually occurs soon after eating (32).|
|•||Gastrointestinal inflammation: Some of the children suffering from migraine with or without aura have been found to have oesophygitis, gastritis of corpus, antral gastritis or duodenitis. It is postulated that there is a gastrointestinal origin of these patients' complaints. findings provide evidence that recurrent abdominal pain is an early expression of migraine and strongly support a causal link between recurrent abdominal pain and migraine(33).|
|•||Female sex hormones fluctuatations: these fluctuations may trigger, intensify, or alleviate migraine. Pharmacological management of migraine in pregnant women must be conservative because of the risks of injury and dependence to the fetus and newborn (34). Motilium and Voltaren have been successfully used for controlling vascular headache developing as a side effect of contraceptive tablets. In case of migraine associated with dysmenorrhoea and/or premenstrual tension the management with triphasic hormone proved to be of therapeutic value (35).|
|•||Minor trauma to the head or whiplash neck injury: ("post-traumatic migraine"-PTM). " The neurologic literature has placed excessive emphasis on compensation neurosis and psychological factors in the etiology of chronic headaches after minor trauma. Physicians must be aware of PTM, as it is both common and treatable (36).|
|•||Low back pain: it has been found that in many patients, headache was found to have begun or exacerbated markedly after onset of low back pain. Potential mechanisms for explaining the high prevalence of migraine following low back pain, include increased muscle tension, psychosocial factors, and analgesic overuse(37).|
|•||Migraine and the eating disorders, particularly bulimia nervosa: Bulimics appear to be more sensitive to the induction of severe migrainous headaches than normal controls following challenge with the 5-HT agonist (38).|
|•||Nitric oxide (NO): it may play a key role in migraine and other vascular headaches since glyceryl trinitrate (a donor of NO) and histamine (which probably activates endothelial NO formation) both cause a pulsating dose-dependent headache with several migrainous characteristics. At relatively high doses of glyceryl trinitrate, migraine sufferers develop stronger and more migraine-like headaches and more pronounced cerebral arterial dilatation than normal controls (39).|
|•||A Common denominator, namely, high levels of blood lipids and free fatty acids are underlying factor in the development of migraine headaches. Biological states that may cause increases in free fatty acids and blood lipids include: high dietary fat intake, obesity, insulin resistance, vigorous exercise, hunger, consumption of alcohol, coffee, and other caffeinated beverages, oral contraceptives, smoking, and stress trigger migraine attack. Elevated blood lipids and free fatty acids are associated with increased platelet aggregability, decreased serotonin, and heightened prostaglandin levels. These changes lead to the vasodilatation that precedes migraine headache (40).|
UNDERSTANDING THE PATHOPHYSIOLOGY OF MIGRAINE ASSISTS IN TREATMENT:
It is useful to conceptualize the patient with migraine as having an inherited susceptibility to headache with altered migrainous threshold. The expression of an altered migrainous threshold in headache-prone persons may depend on the balance between inhibitory and excitatory neurocircuits that are influenced by a complex interplay of exogenous and endogenous factors.
The best preventive strategy recognizes the multifactorial nature of migraine and attempts to increase the migrainous threshold through both pharmacological and non-pharmacological interventions.
The serotonergic system:
It consists of the brain stem, with its descending and ascending circuitry, including the ascending pain-modulating projections from the midbrain raphe nuclei
The neural activity within this serotonergic system is an important precursor to migraine.
Serotonin (5-hydroxytryptamine [5-HT])
It is a biogenic amine that is widely distributed throughout the body. It is considered the serotonergic brain stem generator. Any changes of serotonin can alter cranial circulation and trigger a vascular phase. This neurovascular reaction not only produces constriction or dilation of intracranial and extracranial arteries but also activates the nociceptive trigeminal vascular system. Neural connections exist between the cerebral blood vessels and the trigeminal nerve. Stimulation of the trigeminal sensory C fibers by any of the triggering factors releases vasoactive neuropeptides. These vasoactive neuropeptides include, substrate P and calcitonin gene-related polypeptide and neurokinin A, an outcome that results in a neurogenic or sterile inflammation, which is blocked by 5-HT sub 1 receptor agonists such as sumatriptan or dihydroergotamine (DHE ).
Seven classes of serotonin receptors have been identified.
Symptomatic agents are believed to act as agonists at the 5-HT sub 1 receptor site. They act either peripherally or centrally.
Prophylactic agents act as antagonists at the 5-HT sub 2 receptor site. They act centrally by "stabilizing" the serotonergic system.
ASSESSMENT OF THE PATIENT WITH MIGRAINE
A detailed history is of paramount importance for an accurate diagnosis
of migraine. The physician should ask why the patient is seeking medical attention. The history should include the following factors:
|•||Age at onset.|
|•||Site of pain.|
|•||Frequency and duration of pain.|
|•||Character, intensity and mode of onset of headache.|
|•||Time between onset to peak pain.|
|•||Associated neurologic, ophthalmologic, autonomic or systemic symptoms.|
|•||Sequence of symptoms.|
|•||Aggravating or precipitating factors.|
|•||Prior and current medication use including dose, dosage schedule, and efficacy.|
|•||History of head trauma.|
|•||Results of prior neuroimaging studies.|
|•||Family history of similar diseases.|
|•||A diary can be helpful for documentation of headache frequency, intensity,
compliance, and response to treatment. In addition, a diary may disclose patterns related to lifestyle, diet, menses, or medication overuse.