Personal view: Modelling pain mechanisms of migraine without aura

Introduction: This review aims to model migraine nociception. Methods: Personal experience and litterature. Results: Genetic and environmental factors in combination decide whether a person suffers from migraine. Endogenous and/or exogenous factors precipitate the individual attacks. Nociception takes place around blood vessels. There is a growing understanding of the molecular pathophysiological mechanisms of migraine from human provocation studies. Rodent models of migraine are necessary to understand the complex interrelation between the many putatively involved molecules and tissues but their relevance for human migraine is uncertain. The crucial element in migraine nociception is a unit consisting of endothelial cells, vascular smooth muscle cells, perivascular nerve fibers (trigeminal, parasympathetic and sympathetic) and mast cells. Attacks may start outside the brain by humoral or neurogenic activity releasing nociceptive substances around blood vessels. They may also (perhaps more often) start by the brain generating efferent activity in autonomic and somatic nerves. Conclusion: Human and rodent studies can quickly uncover the "mystery of migraine".