Light and electron microscopic study of the distribution of substance immunoreactive fibers and neurokinin-1 receptors in the skin of the rat lower lip

Cutaneous antidromic vasodilatation and plasma extravasation, two phenomena that occur in neurogenic inflammation, are partially blocked by substance P (SP) receptor antagonists and are known to be mediated in part by mast ce ll-released substances, such as histamine, serotonin, and nitric oxide. In an attempt to provide a morphological substrate for the above phenomena, we applied Light and electron microscopic immunocytochemistry to investigate the pattern of SP innervation of blood vessels and its relationship to mast cells in the skin of the rat lower lip. Furthermore, we examined the distr ibution of SP (neurokinin-1) receptors and their relationship to SP-immunor eactive (LR) fibers. Our results confirmed that SP-IR fibers are found in c utaneous nerves and that terminal branches are observed around blood vessel s and penetrating the epidermis. SP-IR fibers also innervated hair follicle s and sebaceous glands. At the ultrastructural level, SP-IR varicosities we re observed adjacent; to arterioles, capillaries, venules, and mast cells. The varicosities possessed both dense core vesicles and agranular synaptic vesicles. We quantified the distance between SP-IR varicosities and blood v essel endothelial cells. Sla-IR terminals were located within 0.23-5.99 mum from the endothelial cell layer in 82.7% of arterioles, in 90.2% of capill aries, and in 86.9% of venules. Although there was a trend for SP-IR fibers to be located closer to the endothelium of venules, this difference was no t significant. Neurokinin-1 receptor (NK-lr) immunoreactivity was most abun dant in the upper dermis and was associated with the wall of blood vessels. NK-lr were located in equal amounts on the walls of arterioles, capillarie s, and venules that were innervated by SP-IR fibers. The present results fa vor the concept of a participation of SP in cutaneous neurogenic vasodilata tion and plasma extravasation both by an action on blood vessels after bind ing to the NK-lr and by causing the release of substances from mast cells a fter diffusion through the connective tissue. (C) 2001 Wiley-Liss, Inc.