ATP released from tissues can act at P2X receptors expressed on primary afferent neurones. It is becoming clear that this subserves sensations such as taste, chemoreception in the carotid body, and distension of some hollow viscera. ATP can also be released during inflammation, and the resulting potentials in primary afferents come to be interpreted centrally as pain. P2X₂ and P2X₃ subunits are found in a subset of small-diameter, primary afferent neurones, some of which are also sensitive to capsaicin. There is considerable evidence that the functional receptor is a P2X_2/3heterotrimer. This is supported by experiments using antagonists selective for P2X₃ subunit-containing receptors, studies with antisense oligonucleotides to reduce P2X₃ subunit levels, and work on P2X₃ knock-out mice. P2X₄ and P2X₇ receptors also appear to play a role in sensation of chronic inflammatory and neuropathic pain. The expression of these subtypes on dorsal horn microglia appears to be important for the plastic rewiring that sustains these pain states.