ABSTRACT
This review highlights the progress from the initial finding of neurogenic inflammation up to the most recent development in the field of sensory nerves research, focusing on their roles in the microvasculature and the skin. Recent discovery of Transient Receptor Potential (TRP) channels highlight their important roles in detecting a range of environmental stimuli, including chemical and temperature. This provides us novel mechanisms for driving neurogenic inflammation upstream of neuropeptide release in addition to promising potential therapeutic targets in various diseases, including pain, itching and skin inflammation.
Subject(s)
Neurogenic Inflammation/physiopathology , Sensory Receptor Cells/physiology , Skin/innervation , Animals , Cell Communication , Dermatitis/physiopathology , Humans , Irritants/toxicity , Keratinocytes/physiology , Microcirculation/physiology , Nerve Tissue Proteins/physiology , Neuralgia/physiopathology , Neuropeptides/physiology , Nociception/physiology , Nociceptors/physiology , Physical Stimulation , Pruritus/physiopathology , Skin/blood supply , Transient Receptor Potential Channels/physiology , Vasodilation/physiologyABSTRACT
Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide. Discovered 30 years ago, it is produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP has two major forms (α and ß). It belongs to a group of peptides that all act on an unusual receptor family. These receptors consist of calcitonin receptor-like receptor (CLR) linked to an essential receptor activity modifying protein (RAMP) that is necessary for full functionality. CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. It is concluded that CGRP is an important peptide in mammalian biology, but it is too early at present to know if new medicines for disease treatment will emerge from our knowledge concerning this molecule.
