Figure 2.

Schematic diagram depicting events following injury to skin. Injury (1) is often followed by activation of mast cells and release of histamine. Histamine then activates sensory neurones via H₁ receptors (2) to stimulate orthodromic stimulation to spinal cord and antidromic stimulation to surrounding skin that leads to neuropeptide release. Substance P can act via NK₁ receptors on endothelial cells of postcapillary venules or possibly by stimulating further histamine release from mast cells, to mediate plasma extravasation at the site of trauma (3). Substance P can also increase blood flow; however, it is CGRP, acting via CGRP receptors that is best known as a potent and long lasting microvascular dilator (4) and probably the mediator of the flare that surrounds the site of injury.