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Current Pain and Headache Reports

, Volume 16, Issue 3, pp 270–277 | Cite as

Endogenous Mechanisms Underlying the Activation and Sensitization of Meningeal Nociceptors: The Role of Immuno-Vascular Interactions and Cortical Spreading Depression

  • Dan Levy
Migraine Headache (F Taylor, Section Editor)

Abstract

Migraine is considered one of the most prevalent neurological disorders but its underlying pathophysiology is poorly understood. Over the past two decades, it became widely accepted that activation of primary afferent nociceptive neurons that innervate the intracranial meninges serves as a key process that mediates the throbbing head pain of migraine. Knowledge about the endogenous factors that play a role in promoting this neural process during a migraine attack slowly begins to increase, and a better understanding remains one of the holy grails in migraine research. One endogenous process, which has been invoked as a major player in the genesis of migraine pain, is cortical spreading depression (CSD). Until recently, however, this notion was only supported by indirect evidence. Recently, electrophysiological data provided the first direct evidence that CSD is indeed a powerful endogenous process that can lead to persistent activation of meningeal nociceptors and the migraine pain pathway. CSD has been suggested to promote persistent sensitization and ensuing activation of meningeal nociceptors through a mechanism involving local neurogenic inflammation including the activation of mast cells and macrophages and subsequent release of inflammatory mediators. Local action of such nociceptive mediators can increase the responsiveness of meningeal nociceptors. Recent studies provided key experimental data implicating complex meningeal immuno-vascular interactions, in particular, the interplay between proinflammatory cytokines, the meningeal vasculature and immune cells, in enhancing the responses of meningeal nociceptors.

Keywords

Meningeal nociceptors Sensitization Migraine headache Tumor necrosis factor alpha TNF-alpha, TNF-α Vascular COX Cyclooxygenase Cortical spreading depression 

Notes

Disclosure

No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. 1.Headache Research Laboratory, Department of Anesthesia, Critical Care and Pain MedicineBeth Israel Deaconess Medical Center and Harvard Medical SchoolBostonUSA

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