Neurogenic inflammation and its role in migraine

• Published in: Seminars in immunopathology Vol. 40; no. 3; pp. 301 - 314
• Main Author: Ramachandran, Roshni
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2018; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Calcitonin; Calcitonin Gene-Related Peptide - metabolism; Cortex; Cortical spreading depression; Degranulation; Edema; Etiology; Extravasation; Headache; Humans; Immunology; Inflammation; Innervation; Internal Medicine; Meninges; Migraine; Migraine Disorders - metabolism; Neurogenic Inflammation - metabolism; Neurons - metabolism; Neuropeptides; Nociceptors; Pain; Pain perception; Phenotypes; Review; Substance P; Substance P - metabolism; Trigeminal ganglion; Vasodilation; Calcitonin gene related peptide (CGRP); Plasma protein extravasation; Neurogenic inflammation; Meningeal nociceptors; Mast cell degranulation; Substance P (SP); Vasodilation
• ISSN: 1863-2297; 1863-2300; 1863-2300
• DOI: 10.1007/s00281-018-0676-y

The etiology of migraine pain involves sensitized meningeal afferents that densely innervate the dural vasculature. These afferents, with their cell bodies located in the trigeminal ganglion, project to the nucleus caudalis, which in turn transmits signals to higher brain centers. Factors such as chronic stress, diet, hormonal fluctuations, or events like cortical spreading depression can generate a state of “sterile inflammation” in the intracranial meninges resulting in the sensitization and activation of trigeminal meningeal nociceptors. This sterile inflammatory phenotype also referred to as neurogenic inflammation is characterized by the release of neuropeptides (such as substance P, calcitonin gene related peptide) from the trigeminal innervation. This release leads to vasodilation, plasma extravasation secondary to capillary leakage, edema, and mast cell degranulation. Although neurogenic inflammation has been observed and extensively studied in peripheral tissues, its role has been primarily investigated in the genesis and maintenance of migraine pain. While some aspects of neurogenic inflammation has been disregarded in the occurrence of migraine pain, targeted analysis of factors have opened up the possibilities of a dialogue between the neurons and immune cells in driving such a sterile neuroinflammatory state in migraine pathophysiology.