Figure 1.

Schematic diagram outlining the relationship of mast cells, nociceptors, and NGF as well as how this system is activated as a consequence of peripheral injury. Skin injury leads to release of cytokines, such as tumor necrosis factor-α and IL-1β, which activate cells, such as keratinocytes and fibroblasts, to release NGF. The NGF can activate nociceptors directly but, in addition, can cause mast cells to degranulate their products, including 5-HT, histamine, and NGF. This endogenous source of NGF seems to be more potent than exogenous NGF in sensitizing nociceptors (see text for further details).