Nociceptive afferent fibers innervating the airways. A and B, TRPV1+ structures in the guinea pig trachea. TRPV1+ fibers are noted (arrows) between the smooth muscle (sm) of the trachealis muscle and the epithelium (ep) and also (double arrows) in and outside the smooth muscle layer. Asterisk indicates cartilage. From [115]. C, guinea pig trachea stained for TRPV1 (green) and pan-neuronal pgp9.5 (red). TRPV1+ fibers mainly noted in subepithelial plexus (asterisk), whereas pgp9.5+ fibers noted in plexus, epithelial (ep) and smooth muscle (sm). From [115]. D, guinea pig trachea stained for substance P (SP, green) and α3 Na+/K+ ATPase (red). Substance P+ fibers noted within the epithelium (E) and beneath the tracheal smooth muscle (SM). α3+ terminals have a complex arbor, do not express substance P and are found exclusively within the smooth muscle. Arrowheads denote putative parental axons of α3+ fibers and substance P+ fibers projecting to the smooth muscle layer together. Taken from [54]. E, guinea pig tracheal epithelium stained for TRPV1 (red) and substance P (SP, green). Most TRPV1+ fibers also express substance P (double arrows), but a minor subset does not express substance P (arrows). From [115]. F, neuroepithelial bodies from rat lungs stained for TRPV1 (green) and calbindin D (red). Calbindin D is expressed in both the neuroendocrine cells of the NEB and in a subset of thin fibers (open arrows) and thick fibers (open arrowheads) innervating the NEB. TRPV1+ fibers (arrows) do not express calbindin D. From [109]. G, neuroepithelial bodies from rat lungs stained for TRPV1 (green) and CGRP (red). CGRP is expressed in both the neuroendocrine cells of the NEB and in thin fibers innervating the base of the NEB (arrowheads). TRPV1+ fibers (arrows) innervating the NEB also express CGRP. From [109]. H and I, guinea pig lung stained for TRPV1 (green) and pan-neuronal pgp9.5 (red). Fibers expressing pgp9.5 and TRPV1 (double arrows) innervate bronchiole (star), blood vessel (large asterisk) and alveolar tissue. Some pgp9.5+ fibers do not express TRPV1 (arrows). Small asterisks indicate non-specifically labeled white blood cells. From [115]. Scale denotes 200μm (A), 100μm (B), 50μm (D, H), 20μm (C, E, I) or 10μm (F, G).