Pain, General | June 10, 2014 | Author: The Super Pharmacist
Migraine is a recurring type of primary headache which is moderate to severe in intensity and has a pulsating quality. Although it is typically one-sided, it may occur anywhere on the head, neck, and face – or all over. In up to a third of cases, migraine is associated with visual or sensory symptoms—collectively known as an aura—that arise most often before the head pain but that may occur during or afterward.1 At its worst, it is associated with sensitivity to light, noise, and/or smells. Nausea is one of its most common symptoms, worsening with activity. There are several types of migraine, including:
Based on a study conducted by the BEACH (Bettering the Evaluation and Care of Health) program (a continuous national study of general practice activity in Australia), the prevalence of migraine among Australians is estimated at 11.5% of the population or nearly three million people.2 The study also identified significantly higher prevalence rates for females (14.9%) than for males (6.1%).2 Migraine prevalence has been shown to vary by race and geography. In the U.S., it is highest in Caucasians, intermediate in African Americans, and lowest in Asian Americans.3 Similarly, a meta-analysis of prevalence studies suggested that migraine is most common in North and South America, similar in Europe, but lower in Africa, and often lowest in studies from Asia.3 The data suggest that race-related differences and genetics may contribute to risk.
A survey conducted by Stollznow Research, as a partnership initiative of Headache Australia and Merck Sharp & Dohme,4 demonstrated the profound impact of migraine on quality of life. The condition limits sufferers both personally and professionally by causing reduced family, social and recreational activities, lost work productivity and even foregone career opportunities. A particularly distressing finding is that the majority of migraine patients (83%) do not expect their condition to improve substantially in the near future.4
In the 20th century, understanding of the pathogenesis of migraine was dominated by the vascular theory. First proposed by Willis (1664) and best described by Wolff (1948), the theory attributed the pain of migraine to the dilation of cranial blood vessels.Wolff's vascular theory of migraine consisted of 2 elements:
Wolff's vascular theory of migraine was based on three observations:
According to the vascular theory, migraine headache is caused by a rebound vasodilation that results in a mechanical depolarisation of pain receptors within the walls of the engorged intra- and extracerebral vessels.7 One of the mainstays of the vascular theory was the fact that it was consistent with the observed headache inducing effects of vasodilating drugs, such as nitroglycerin, and the therapeutic effects of ergotamines, which were known to be potent vasoconstrictors. In 2008, a landmark article by Schoonman et al8 showed conclusively that intracranial vasodilatation is not related to the painful phase of migraine. These investigators, for the first time, were able to directly and accurately measure the diameters of most of the major intracranial and some of the extracranial vessels, both during migraine and between migraine attacks, on left and right sides, during unilateral (headache on one side of the head) migraine. They found that none of the vessels measured appeared to dilate during the migraine attack.8 As a result of these anomalous findings, the vascular theory was superseded by the neurovascular theory.
The neurovascular theory holds that a complex series of neural and vascular events initiates migraine.9 According to this theory, migraine is primarily a neurogenic process with secondary changes in cerebral blood flow.10 At baseline, a patient with migraine who is not having any headache has a state of neuronal hyperexcitability in the cerebral cortex, especially in the occipital cortex.11 This finding has been demonstrated in studies of transcranial magnetic stimulation and with functional magnetic resonance imaging (MRI). This observation explains the special susceptibility of the migrainous brain to headaches.12 This is similar to the patient with epilepsy who also has interictal (between seizures) neuronal irritability.13
Cortical spreading depression (CSD) was first described by Leao14, 15 who observed a depression of electrical activity recorded on the scalp (EEG activity) that moved across the cortex at a rate of 3-6 mm/minute. It has been observed in clinical practice that the migraine aura, a transient neurological disturbance16 that moves slowly across the visual field, has the same rate of progression.17 Olesen et al18 identified a spreading reduction in cerebral blood flow in patients with migraine aura. The CSD hypothesis completely reverses the vascular hypothesis with the primary event being neural and brain blood flow changes being secondary to changes in neuronal activity.19 Further support for this theory is derived from cerebral blood flow changes seen with SPECT20 and perfusion-weighted MRI21 which demonstrate a spreading reduction of blood flow during aura. This theory has many potential explanations further perplexing scientists and medicos.
Peripheral sensitisation: The trigeminovascular system consists of neurons in the trigeminal nerve that innervate cerebral blood vessels. Activation of the trigeminovascular system by CSD stimulates pain receptors on blood vessels within the brain to release inflammatory mediators. These inflammatory compounds irritate the cranial nerve roots, particularly the trigeminal nerve, which is responsible for conveying sensory information from the face and much of the head to the brain. This chemical irritation or peripheral sensitisation of the trigeminal nerve converts high-threshold pain receptors into low-threshold pain receptors.22 It explains the intracranial hypersensitivity that occurs in migraine (e.g. worsening of the headache with coughing or physical activity) and the throbbing nature of migraine pain (sensitised pain receptors become hyper-responsive to the otherwise innocuous and unperceived rhythmic fluctuations in intracranial pressure produced by normal arterial pulsation).23, 24
Central sensitisation: Peripheral (the outer parts of the body) sensitisation frequently leads to central (relating to the brain and spinal cord) sensitisation. Central sensitisation refers to the hyper-responsiveness or hyper-excitability of the second-order neurons in the trigeminocervical complex in the brain. This process explains the facial and scalp allodynia (pain experienced from stimulus that does not normally provoke pain) and neck stiffness that often occurs in migraine. The sensitisation process progresses the patient’s cerebral cortex into a state of hyper-excitability which ultimately leads to the transformation of episodic migraine to the chronic form of migraine.26
Serotonin: Serotonin (also known as 5-HT) is a neurotransmitter that is involved in the communication process of the central nervous system. Although other neurotransmitters may be involved in the pathophysiology of migraine, the serotonergic system is believed to play an important role. Documented changes in serotonin processing and metabolism during a migraine attack suggest that migraine is a result of a central neurochemical imbalance secondary to dysfunction of the serotonergic system. Although the exact series of events involved is not fully understood, low levels of serotonin appear to cause activation of the trigeminovascular system.27
Dopamine: Early symptoms prior to the onset of the migraine (mood changes, yawning, drowsiness, food cravings), accompanying symptoms experienced during an attack (nausea, vomiting, low blood pressure) and symptoms experienced in the later stages of an attack (mood changes, drowsiness, tiredness) may be related to dopaminergic activation. Some authors have proposed a dopaminergic basis for migraine.30 From this perspective, a blockade of dopaminergic hyper-responsive receptors can be considered as a rationale for the therapy of migraine. Dopamine receptor blockers (dopamine antagonists) (e.g. prochlorperazine) completely relieve almost 75% of acute migraine attacks.
Brainstem activation. PET scanning in patients having an acute migraine headache demonstrates activation of the contralateral pons (a part of the brain stem which is the opposite side to the symptom of migraine), even after medications abort the pain.29 Increases in regional cerebral blood flow of 11% were measured in the medial brainstem on the opposite side of the body to the headache. Effective treatment of the headache with an injectable sumatriptan did not reduce the midbrain cerebral blood flow. Based on these findings, it has been proposed that migraine attacks are initiated by a brainstem generator either through direct abnormal activation or through a failure of inhibition.
Migraine is considered a complex genetic disorder. Approximately 70% of patients have a first-degree relative with a history of migraine. The risk of migraine is increased 4-fold in relatives of people who have migraine with aura.28 Migraine headache generally shows a multifactorial inheritance pattern. It should be considered possible that migraines can be prevented and treated, even cured in the future. Rational drug design, genetic mapping and further understanding will play important roles in the effective treatment for this life effecting condition.