Pathophysiology of migraine--from molecular to personalized medicine.

ABSTRACT

INTRODUCTION: Understanding of migraine pathophysiology has substantially improved over the last two decades. As a result, migraine is now mainly considered to be a disorder of the brain, rather than one of the vasculature or the meninges. PATHOPHYSIOLOGY Although it remains speculative how exactly they relate to each other, the following three processes are important in migraine 1. Cortical spreading depression is a wave of intense depolarization, it starts in the occipital lobe, propagates through the brain and is followed by a period of suppressed activity. 2. Activation of the trigemonovascular system causes the release of neuropeptides (e.g. calcitonin gene-related peptide, substance P) from the peripheral trigeminal nerve endings. These neuropeptides are thought to play a role in causing and maintaing headache. 3. Sensitization of peripheral and central brain areas, it is thought that pulsating quality of migraine headache is caused by a process of peripheral sensitization. Cutaneous allodynia is a marker of central sensitization. LINK BETWEEN AURA AND HEADACHE The view that the aura is caused by cortical spreading depression has become generally accepted, and the same is true for the view that activation of the trigemonovascular system underlies migraine headache. However, the relationship between the aura and the activation of the trigemonovascular system and the start of headache remains elusive. GENETICS OF MIGRAINE One of the most important aspects of the pathophysiology of migraine is the hereditary nature of the disorder. CONCLUSION: Identification of polymorphisms and genetic biomarkers should help us to understand migraine pathophysiology better and thus enable the development of specific, effective "individually-tailored treatment" for each particular migraine patient (personalized medicine).