Migraine: A Brain State
Migraine: A Brain State
A number of neurochemical mediators have been implicated in the transition from the wake to the sleep state. The transition to the migraine state may similarly involve changes in the levels of a variety of neurochemical mediators. Parallels between premonitory symptoms in migraine and those evoked by administration of dopamine receptor agonists have led to the hypothesis that dopamine may be one of these mediators. Orexins have also been proposed as potential mediators of both migraine and sleep. Other interesting candidates for mediators of the migraine state that have been studied extensively in the context of sleep are the purines (ATP and adenosine). Extracellular adenosine levels increase during wakefulness, and a longstanding hypothesis has been that this increased adenosine plays a role in sleep induction by activation of receptors that inhibit neuronal activity. An appealing aspect of this hypothesis is that it links cellular energy metabolism (adenosine is a product of ATP breakdown) and the drive to sleep, thus representing a homeostatic mechanism that may act in parallel with the hypothalamic circadian clock. ATP levels have been reported to rise during early stages of sleep in animals, supporting the hypothesis that one function of sleep is to restore a balance between ATP and adenosine. Interictal magnetic resonance spectroscopy studies show a decrease in brain phosphocreatine content, and a decrease in occipital lobe ATP interictally in some migraine patients, consistent with an alteration in ATP and other high energy substrates in migraine. Although there is no direct evidence for a role for adenosine in migraine, the migraine therapeutic effects of caffeine, a nonselective adenosine receptor antagonist, provide support for such a role. It is also interesting to speculate that adenosine could play a role in the fatigue, yawning and asthenia associated with migraine. The development of selective adenosine receptor antagonists for other indications may provide an opportunity for more definitive investigation of a hypothesized role for adenosine in the migraine state.
Neurochemical Mediators of the Migraine State
A number of neurochemical mediators have been implicated in the transition from the wake to the sleep state. The transition to the migraine state may similarly involve changes in the levels of a variety of neurochemical mediators. Parallels between premonitory symptoms in migraine and those evoked by administration of dopamine receptor agonists have led to the hypothesis that dopamine may be one of these mediators. Orexins have also been proposed as potential mediators of both migraine and sleep. Other interesting candidates for mediators of the migraine state that have been studied extensively in the context of sleep are the purines (ATP and adenosine). Extracellular adenosine levels increase during wakefulness, and a longstanding hypothesis has been that this increased adenosine plays a role in sleep induction by activation of receptors that inhibit neuronal activity. An appealing aspect of this hypothesis is that it links cellular energy metabolism (adenosine is a product of ATP breakdown) and the drive to sleep, thus representing a homeostatic mechanism that may act in parallel with the hypothalamic circadian clock. ATP levels have been reported to rise during early stages of sleep in animals, supporting the hypothesis that one function of sleep is to restore a balance between ATP and adenosine. Interictal magnetic resonance spectroscopy studies show a decrease in brain phosphocreatine content, and a decrease in occipital lobe ATP interictally in some migraine patients, consistent with an alteration in ATP and other high energy substrates in migraine. Although there is no direct evidence for a role for adenosine in migraine, the migraine therapeutic effects of caffeine, a nonselective adenosine receptor antagonist, provide support for such a role. It is also interesting to speculate that adenosine could play a role in the fatigue, yawning and asthenia associated with migraine. The development of selective adenosine receptor antagonists for other indications may provide an opportunity for more definitive investigation of a hypothesized role for adenosine in the migraine state.
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