ATP receptors in pain

Extracellular ATP has been known to activate sensory neurons via the ATP-gated ion channels P2X receptors, leading to the proposal that the P2X receptors may play a role in signal transduction of pain from the peripheral site to the spinal cord in vivo. P2X₃ receptors are expressed in capsaicin-sensitive small-sized dorsal root ganglion (DRG) neurons, and they are involved in the generation of rapidly desensitizing inward current and evoking nocifensive behavior and thermal hyperalgesia. Heteromeric P2X_2/3 (P2X₂ and P2X₃) receptor is expressed in capsaicin-insensitive primary afferent fibers, and its activation leads to the generation of slow desensitizing currents and induction of mechanical allodynia. In addition, accumulating information suggests the involvement of G protein-coupled ATP receptors in the modulation of the generation and transmission of pain.