Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats: Involvement of heteromeric P2X(2/3) receptor signaling in capsaicin-insensitive primary afferent neurons

Extracellular ATP has been known to activate sensory neurons via the ATP-ga ted ion channels P2X receptors, indicating that the P2X receptors may play a role in signal transduction of pain from the periphery to the spinal cord in vivo. Here, we found a novel nociceptive response induced by ATP, mecha nical allodynia (hypersensitivity to innocuous mechanical stimulus). Inject ion of alpha, beta-methylene ATP (alpha beta meATP), an agonist to P2X rece ptor, into plantar surface in rats produced the mechanical allodynia along with previously described nocifensive behavior and thermal hyperalgesia. Th is allodynic response was blocked by pretreatment with the P2 receptor anta gonist pyridoxal-phosphate- 6-azophenyl-2',4'-disulfonate. Interestingly, o nly the mechanical allodynia evoked by abmeATP selectively remained in neon atal capsaicin-treated adult rats that had selectively lost the capsaicin-s ensitive neurons. ATP has been shown to produce two distinguishable electro physiological responses (inward currents with rapid and slow desensitizatio n) in dorsal root ganglion (DRG) neurons. In the present electrophysiologic al experiment, the percentage of DRG neurons that responded to alpha beta m eATP with slow desensitizing inward current remained constant in capsaicin- treated rats, whereas the percentage that responded with rapid desensitizin g current dramatically decreased. Taken together with our previous finding that the alpha beta meATP-activated slow desensitizing current in DRG neuro ns is mediated by heteromeric P2X(2/3) (P2X(2) and P2X(3)) receptors, it is hypothesized that activation of heteromeric P2X(2/3) receptors in peripher al terminals of capsaicin-insensitive primary afferent fibers leads to the induction of mechanical allodynia.