Chemosensitive afferent nerves expressing the capsaicin/TRPV1 (transient receptor potential vanilloid receptor-1) receptor are not only involved in the transmission of nociceptive impulses toward the central nervous system, but also play pivotal roles in the initiation and modulation of vascular, inflammatory, and immune reactions in a variety of organs, including the skin. These sensory nerves exert their efferent/local regulatory functions primarily via the release of vasoactive neuropeptides such as calcitonin gene-related peptide and substance P from their terminals upon antidromic or orthodromic stimulation. The chemical changes induced in the neural microenvironment by tissue injury or inflammation may promote the release of proinflammatory sensory neuropeptides and lead to augmentation of the inflammatory response. In turn, the release of anti-inflammatory peptides from sensory nerves or from inflammatory cells may result in an inhibition of cutaneous vascular reactions. The available experimental evidence implicates capsaicin-sensitive sensory nerves in the pathogenesis of certain skin diseases and maladies with cutaneous manifestations. The development of potent nonpeptide antagonists of sensory neuropeptides, the capsaicin/TRPV1 receptor, and the proteinase-activated receptors may offer new possibilities for the management of certain skin diseases and the itch and pain associated with altered sensory nerve functions.
ASJC Scopus subject areas
- Clinical Neurology