Nerve fibers containing a variety of neuropeptides, including substance P and CGRP, have been demonstrated in human skin. Intradermal injection of substance P results in an immediate wheal-and-flare reaction , whereas the main effect of CGRP is a long-lasting (4–6 hours) intense erythema. Additionally, CGRP potentiates edema formation evoked by mediators such as substance P.
This work suggested that neuropeptides may have an important role to play in both the allergen-induced EPR and LPR.
Previous work on two subjects with impaired sensory function (one with sensory denervation due to trauma, the second after administration of local anesthetic) showed that stimulation of mast cells with anaphylactogenic anti-IgE resulted in a wheal, but the complete absence of a flare, corroborating evidence that the flare in the EPR is due to a neurogenic reflex mechanism.
However, in both of these subjects, there was no apparent reduction in the LPR on the sensory-deprived site as compared with a control site, suggesting that while neurogenic inflammation was responsible for the flare of the EPR, it had a limited role in the LPR.
