Causes of Chronic Migraines

Causes of Chronic Migraines Headache is pain in any part of the head that can occur suddenly or gradually and produce a varying amount of pain; in fact, it is the most common form of pain in the United States (U.S. Department of Health and Human Services, 2014). Headache is often divided into two categories, primary and secondary (U.S. Department of Health and Human Services, 2014). A primary headache is one that is due to the headache itself, it is not caused by another problem (U.S. Department of Health and Human Services, 2014). The three types of primary headache include tension headaches, cluster headaches, and migraine headaches (U.S. Department of Health and Human Services, 2014). Secondary headaches, on the other hand, are headaches that are caused by something else (U.S. Department of Health and Human Services, 2014). Examples of secondary headaches include headaches from an illness, headaches from a medication, sinus headaches, cervicogenic headaches (which are headaches related to an underlying neck condition, like degenerative disc disease), and headache due to a brain tumor or aneurysm (U.S. Department of Health and Human Services, 2014). Migraine headaches are one of the most common forms of headache (Davanzo, Bua, Paloni, Facchina, 2014). Migraines are considered a neurological condition (Schwedt, 2014; Silberstein, 2014). They often manifest as recurrent attacks of throbbing, frequently unilateral headaches with associated features, including: nausea, vomiting, photophobia, and phonophobia (Pietrobon Moskowitz, 2012; Schwedt, 2014). Migraines can be further subdivided into episodic or chronic (Schwedt, 2014). Episodic migraine sufferers have less than 15 headache days a month, whereas chronic sufferers have at least 15 headache days a month for at least three months, and at least eight headaches that have symptoms consistent with a full-blown migraine attack (Ferrari, 2013; Schwedt, 2014). Chronic migraine is a common disorder; it impacts people during their most productive years of life, has tremendous costs to the individual and society, and is associated with a variety of comorbid disorders (Schwedt, 2014). Chronic migraine typically develop through a process called migraine transformation, which is a slow increase in the frequency of headaches, usually over a period of months to years (Schwedt, 2014). Chronic migraine is diagnosed based on the patient’s symptoms by excluding other causes of headache (Schwedt, 2014). A general physical and neurological exam should be performed on each patient and attention should be paid to the patient’s neck, shoulders, temporal artery pulses, and tempromandibular joint; if any abnormalities are found on the neurological exam, a secondary headache should be suspected and the patient should undergo further evaluation (Schwedt, 2014). Many risk factors are associated with a higher likelihood of transformation from episo dic to chronic migraine and include obesity, excessive caffeine intake, low socioeconomic status, and major life changes like marriage or divorce, to name a few (Schwedt, 2014). Common conditions comorbid with chronic migraine include other neurological disorders, gastrointestinal problems, and cerebrovascular disease (Pietrobon Moskowitz, 2012; Schwedt, 2014). Compared to people with episodic migraines, patients with chronic migraine are twice as likely to have certain psychiatric disorders, including anxiety, depression, and bipolar disorder (Schwedt, 2014). The pathophysiology of chronic migraine is complicated and not fully understood (Schwedt, 2014). It was once believed that migraines were simply a swelling of the blood vessels in the brain (Pietrobon Moskowitz, 2012). More recent experiments have shown that swelling of the meninges and/or extracranial arteries is neither necessary nor sufficient to cause migraine pain (Pietrobon Moskowitz, 2012). While such swelling is certainly often found during migraines, migraines are no longer assumed to be exclusively a disorder of blood vessels; rather, there are data to suggest that chronic migraine is associated with progressive brain changes, both in brain structure and brain function (Ferrari, 2013; Pietrobon Moskowitz, 2012). Atypical modulation of pain is suspected to play a role in the transformation from episodic to chronic migraine by reducing the inhibition of pain in the regions of the descending pain modulatory pathway in the brain (Schwedt, 2014). Neuroimaging studies of patie nts with chronic migraine have shown both atypical structures of pain processing and atypical pain processing in the brain (Schwedt, 2014). Regions of the brain that participate in sensory discrimination, affect, and the cognitive appraisal of pain are also atypical in migraine sufferers (Schwedt, 2014; Silberstein, 2014). Many studies have found correlations among the extent of these abnormalities and the frequency and severity of migraine headaches, suggesting that these abnormalities could be precursor to the transformation from episodic to chronic migraine (Schwedt, 2014), but more research is necessary to determine the exact role and mechanism of these abnormalities. The trigemininovasular system is currently considered one of the major players in the role of chornic migraine (Pietrobon Moskowitz, 2012; Schwedt, 2014). The trigeminal nerve is the fifth cranial nerve in the body and is the main sensory nerve in the head (Fix Brueckner, 2009). Some researchers believe that the musculature around the trigeminal nerve branches become irritated, which leads to the swelling and pain caused by migraine headaches (Kurlander, Punjabi, Liu, Sattar, Guyuon, 2013). Presently it is speculated that a sensitization of the trigeminal system that innervates cranial tissues, specifically the meninges (which often swell during migraine attacks) leads to a lower threshold for activation (Pietrobon Moskowitz, 2012; Schwedt, 2014). A lower threshold for activation means the system becomes activated more easily, which leads to more migraine attacks, and more migraine attacks therefore increase the likelihood of a chronic migraine diagnosis (Pietrobon Moskowitz, 20 12; Schwedt, 2014). Another line of research that is currently being investigated is cortical hyperexcitability (Schwedt, 2014). The human nervous system is composed of billions of synapses and neurons functioning as part of a large, highly specializes system (Fix Brueckner, 2009). All aspects of behavior are informed by the nervous system, and it can rudimentarily be broken down into excitatory and inhibitory components that facilitate the communication among different neurotransmitters in the brain to determine the level of inhibition of excitation of each response (Fix Brueckner, 2009). Excitation in the brain is mainly associated with the neurotransmitter glutamate (Fix Brueckner, 2009). Recent transcranial magnetic stimulation studies on patients with chronic migraine have shown cortical hyperexcitability, particularly in the occipital cortex of the brain. The occipital cortex is associated with vision, and this makes sense to researchers as visual auras are often associated with migraine attack s (Fix Brueckner, 2009; Schwedt, 2014). A neurotransmitter of interest, particularly with the beginning phase of a migraine attack, is dopamine (Charles, 2012). Some research has shown that dopamine receptor agonists administered to patients produce some of the same symptoms that are experienced by migraine sufferers at the beginning of an attack (Charles, 2012). Conversely, dopamine receptor antagonists administered to patients can reverse those symptoms and have even been suggested to have the ability to prevent the onset of additional migraine attacks (Charles, 2012). While the exact role of dopamine in chronic migraine is unknown, it is certainly an interesting line of future study. Treatments for chronic migraine range from trigger identification and avoidance to risk-factor modification, and include both pharmacological and nonpharmacological components (Schwedt, 2014). A discussion of each type of treatment and the variety of treatments within is beyond the scope of this review, however, some of the most common pharmacological treatments will be highlighted. Pharmacological treatment for migraines can be divided into two categories: abortive drugs, which stop a headache after onset, and prophylactic drugs, which are taken on a regular basis to prevent the onset of a migraine (Davanzo et al., 2014). Those who suffer from chronic migraine are often on a prophylactic regimen, due to the intensity and severity of the headaches (Davanzo et al., 2014). While many drugs are used for chronic migraine prophylaxis, it is important to note that many are prescribed off label; in fact, the only drug approved by the Food and Drug Administration for the treatment of chronic migraine is onabotulinumtoxinA (Schwedt, 2014). OnabotulinumtoxinA, more commonly known as Botox, has been popularized as a series of small injections in the face that reduce the appearance of crow’s feet and frown lines (Oliver, MacDonald, Rajwani, 2006). However, the injections are also used to treat chronic migraine (Schwedt, 2014). Botox is part of a class of medications called neurotoxins (Fix Brueckner, 2009). It has no direct effect on the central nervous system because it cannot penetrate the blood brain barrier, however, it can have some important indirect effects on the central nervous system (Fix Brueckner, 2009; Oliver, MacDonald, Rajwani, 2006). When used to treat chronic migraine, Botox is injected into different muscles in the face to block the nerve signals to those muscles (Fix Brueckner, 2009; Oliver, MacDonald, Rajwani, 2006). Specifically, Botox has been shown to inhibit sensitizations of central trigeminal nerves, which was previously discussed regarding the pathophysiology of chronic migraine (Ol iver, MacDonald, Rajwani, 2006). Triptans are another common class of drugs used for chronic migraine prophylaxis (Davanzo et al., 2014). Triptans are serotonin receptor agonists, meaning they bind to serotonin and increase the response of serotonin at the site of action (Davanzo et al., 2014; Fix Brueckner, 2009). Triptans have a vasoconstriction action on blood vessels, meaning they shrink the size of blood vessels, which is helpful in reducing the pain of migraines some of which can be attributed to swollen blood vessels in the brain (Davanzo et al., 2014). However, the desired effect of vasoconstriction is not limited to just the brain and also constricts other blood vessels, including those in the heart (Davanzo et al., 2014). As a result, patients with any coronary disease should use care when taking triptans (Davanzo et al., 2014). The most commonly prescribed triptan medication is Sumatriptan and is available in multiple forms including pills, injections, and intranasal spray (Davanzo et al., 2014). The inj ections and intranasal spray reach the brain more quickly and are therefore faster acting than the pill which must first get absorbed into the blood stream to take effect (Davanzo et al., 2014). Beta blockers, originally used for the treatment of hypertension and angina, are also often used for migraine prophylaxis (Davanzo et al., 2014). The beta part of beta blockers refers to receptors on blood vessels that are called beta receptors (Fix Brueckner, 2009). Therefore, beta blockers prevent the interaction of certain chemicals with this receptor (Fix Brueckner, 2009). The most commonly prescribed beta blocker for chronic migraine is Propranolol (Davanzo et al., 2014). Propranolol is likely successful in preventing migraine headaches by blocking beta adrenergic receptors, which inhibits swelling of arteries. Additionally, Propranolol may also exhibit its effect by preventing the platelets (the sticky elements of the blood) from sticking together and releasing substances that caused the blood vessels to constrict and dilate. A concern with pharmacological treatment of chronic migraine is the development of medication overuse headaches. These occur when a migraine sufferer uses migraine drugs too frequently, and develops a secondary headache as a result of the medication use (Schwedt, 2014). The treatment includes a drug withdrawal phase, during which time the patient would have to stop taking medication for his migraine or take a medication with different mechanism of action to allow the overused drug to leave his system (Schwedt, 2014). This response is paradoxical because sufferers of chronic migraine often rely on pharmacological treatments to alleviate their pain, but if they take too much they will actually end up exacerbating their pain. About half of chronic migraine sufferers are treated for medication overuse headaches at some point (Schwedt, 2014). A brief overview of the criteria for diagnosis, hypothesized pathophysiology, and pharmacology for the treatment of chronic migraine has been discussed. While there is still much to learn about the pathophysiology of chronic migraine, recent research has increased the understanding and opened up new areas of research to bring scientists closer to a more comprehensive understanding. While many data indicate that chronic migraine is a debilitating condition with great intensity and duration of headaches, and often lead to lost productivity and high costs on society (Schwedt, 2014), there are prophylactic and abortive drugs that can greatly ameliorate the problems caused by migraines. With attention to and modification of risk factors, often in addition to appropriate adherence to these medications, migraine sufferers can live normal, productive lives.