P2X3 receptors and peripheral pain mechanisms

ATP released from damaged or inflamed tissues can act at P2X receptors expressed on primary afferent neurones. The resulting depolarization can initiate action potentials that are interpreted centrally as pain. P2X₃ subunits are found in a subset of small-diameter, primary afferent neurones, some of which are also sensitive to capsaicin. They can form homo-oligomeric channels, or they can assemble with P2X₂ subunits into hetero-oligomers. Studies with antagonists selective for P2X₃-containing receptors, experiments with antisense oligonucleotides to reduce P2X₃ subunit levels, and behavioural testing of P2X₃ knock-out mice, all suggest a role for the P2X_2/3 receptor in the signalling of chronic inflammatory pain and some features of neuropathic pain. The availability of such tools and experimental approaches promises to accelerate our understanding of the other physiological roles for P2X receptors on primary afferent neurones.