Neuroimmune interactions in the development and chronification of migraine headache.

Large-scale genome-wide association analyses have identified loci of migraine risk that encode inflammation-related genes. Other lines of evidence in humans have further implicated immune dysregulation in migraine, including measurements of peripheral proinflammatory factors and neuroimaging studies. Studies in rodents point to immune dysregulation along the trigeminovascular pathway as a major contributor to migraine's pathophysiology. Reciprocal modulation between the immune cells and the meningeal afferent neurons regulates peripheral and central sensitization, leading to persistent headache and its chronification. Microglia–neuron interactions in the trigeminocervical complex may play an important role in the transition from episodic to chronic migraine. Emerging evidence suggests that regulatory T cells participate in the resolution of migraine headaches. Targeting regulatory T cells may restore the balance between immune activation and suppression to reverse chronic headaches. Migraine is highly prevalent and debilitating. The persistent headaches in this condition are thought to arise from the activation and sensitization of the trigeminovascular pathway. Both clinical and animal model studies have suggested that neuroimmune interactions contribute to the pathophysiology of migraine headache. In this review, we first summarize the findings from human studies implicating the dysregulation of the immune system in migraine, including genetic analyses, measurement of circulatory factors, and neuroimaging data. We next discuss recent advances from rodent studies aimed at elucidating the neuroimmune interactions that manifest at various levels of the trigeminovascular pathway and lead to the recruitment of innate and adaptive immune cells as well as immunocompetent glial cells. These cells reciprocally modulate neuronal activity via multiple pro- and anti-inflammatory mediators, thereby regulating peripheral and central sensitization. Throughout the discussions, we highlight the potential clinical and translational implications of the findings. [ABSTRACT FROM AUTHOR]