Interaction of calcitonin gene related peptide (CGRP) and substance P (SP) in human skin

Abstract

Calcitonin gene related peptide (CGRP) and substance P (SP) are neuropeptides that are simultaneously released from nociceptive C-fibers. CGRP is a potent vasodilator, inducing a long-lasting increase in superficial skin blood flow, whereas SP induces only a brief vasodilation but a significant plasma extravasation. CGRP and SP may play important roles in the pathophysiology of various pain states but little is known about their interaction.Different concentrations of SP (ranging from 10−5M to 10−9M) were applied to the volar forearm of 24 healthy subjects via dermal microdialysis. SP was applied either alone or in combination with CGRP10−9M and CGRP 10−6M.As expected, SP induced a transient increase in skin blood flow that decayed shortly after application. This transient blood flow peak was blunted with co-application of CGRP 10−9M and inhibited with co-application of CGRP10−6M. SP alone induced plasma protein extravasation (PPE). However, when CGRP10−6M was added, the PPE significantly increased.Our results demonstrate a complex interaction of the neuropeptides CGRP and SP. CGRP10−6M prevented SP-induced early vasodilation but augmented SP-induced PPE. These interactions might explain why vascular symptoms in chronic pain can differ strikingly between individuals.