ATP has been implicated in the initial algogenic signal via ionotropic P2X receptors in sensory neurons. However, possible roles for metabotropic P2Y receptors in nociceptive signaling have received limited attention in spite of the fact that they are expressed in dorsal root ganglion (DRG) neurons. In the 34th SFN meeting 2004, we showed that epidermal keratinocytes release ATP that propagates Ca2+ wave from keratinocytes to sensory neurons via P2Y2 receptors. The aim of this study is to characterize functional P2Y receptors in DRG neurons in relation to pain behavior. Injection of the P2Y2 and P2Y4 receptor agonist uridine 5'-triphosphate (UTP) into plantar surface in rats produced the mechanical allodynia. The UTP-induced mechanical allodynia was inhibited by suramin or antisense oligonucleotide for P2Y2 receptors. The UTP-evoked pain behavior was different from the P2X receptor agonist alpha-beta-meATP-evoked one in that the former induced only mechanical allodynia whereas the latter induced thermal hy...