Fig. 7.

Phosphorylation of peripheral TRPV1. There are a number of endogenous inflammatory mediators, such as PGE₂, ATP, BK, and ET-1, which are able to act at their respective receptors located on TRPV1-expressing afferent fibers. Through various intracellular signaling cascades, they are able to phosphorylate, and sensitize, TRPV1 (although certain lipids and acid may act directly on TRPV1 itself)—resulting in the lowering of activation thresholds and heightened activity to further stimuli. Furthermore, this effect may also be achieved through Ca²⁺-dependent activation of CaMKII, which also phosphorylates TRPV1. This phosphorylation may lead to both thermal and mechanical hypersensitivity at this site. AC, adenylyl cyclase; PLC13, phospholipase C13. (See section VIII.C for details.)