How are substance P and calcitonin gene-related peptide implicated in the phenomenon of neurogenic inflammation?
Cell bodies in the dorsal root ganglion synthesize substance P and CGRP and transport these peptides by axoplasmic transport both to the central and peripheral terminals of the primary afferents. The peptides are stored in the periphery and can be released when the terminals are depolarized as a result of injury. The targets of substance P in the periphery include mast cells, blood vessels, and a variety of immunocompetent cells. In concert with CGRP, which produces a profound vasodilatation, substance P significantly increases plasma extravasation from postcapillary venules. The extravasation of protein from vessels is accompanied by fluid, producing the characteristic swelling (tumor) of inflammation. The heat and redness (calor and rubor) of inflammation can be accounted for by the neurogenic vasodilatation.
There is considerable evidence that neurogenic inflammation contributes to the pain of migraine. Indeed, triptans block neurogenic inflammation, via an action on 5HT-1B/D receptors located on the terminals of primary afferent nociceptors. Although antagonists of the NK1 receptor failed as a treatment for migraines in clinical trials, antibody-mediated blockade of CGRP shows significant promise as a migraine treatment.
