Two immunohistochemically identified populations of calcitonin gene-related peptide (CGRP)-immunoreactive axons in human skin

Double labelling immunofluorescence has shown two populations of unmyelinated sensory axons in human skin that contain immunoreactivity (IR) to calcitonin gene-related peptide (CGRP). One population also contains IR to substance P (SP), whilst the other also contains IR to somatostatin (SOM). Axons containing both CGRP-IR and SOM-IR comprised more than 75% of CGRP-IR axons associated with the epidermis; the rest of the CGRP-IR axons contained SP-IR. No axons contained both SP-IR and SOM-IR. Some dermal blood vessels were surrounded by axons containing both CGRP-IR and SP-IR, but most CGRP-IR perivascular axons contained SOM-IR without SP-IR. Sweat glands were well supplied with sensory axons containing CGRP-IR and weak SOM-IR but not SP-IR. Therefore, CGRP is a histochemical marker for a larger number of unmyelinated cutaneous afferents in human skin than is SP. CGRP itself may have a role in the mediation of responses to stimulation of at least two populations of sensory axons.