ATP and pain.

Many decades have passed since the pain-producing properties of ATP were demonstrated in both animals and humans. However, the more recent discovery of a family of ion channels for which ATP is a ligand and which are expressed by nociceptive neurons, has led to a resurgence of interest into the physiological and pathophysiological actions of ATP. This article considers the extent to which available evidence supports the notion that ATP receptors might be important novel analgesic targets.

P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP.

Extracellular ATP plays a role in nociceptive signalling and sensory regulation of visceral function through ionotropic receptors variably composed of P2X2 and P2X3 subunits. P2X2 and P2X3 subunits can form homomultimeric P2X2, homomultimeric P2X3, or heteromultimeric P2X2/3 receptors. However, the relative contribution of these receptor subtypes to afferent functions of ATP in vivo is poorly understood.