Activation of peripheral P2X receptors is sufficient to induce central sensitization in rat medullary dorsal horn nociceptive neurons

► ATP contributes to the development of central sensitization (CS) in medullary nociceptive neurons. ► Application of purinergic agonist to the rat tooth pulp induces CS in medullary nociceptive neurons. ► Central sensitization can be blocked by pulp application of the purinergic antagonist TNP-ATP. ► Central sensitization can be attenuated by medullary application of TNP-ATP. Central sensitization and purinergic receptor mechanisms have been implicated as important processes in acute and chronic pain conditions following injury or inflammation of peripheral tissues. This study has documented that application of the P2X1,2/3,3 receptor agonist αβ-meATP (100mM) to the rat tooth pulp induces central sensitization in medullary dorsal horn nociceptive neurons that is reflected in significant increases in mechanoreceptive field size and responses to noxious stimuli and decreased mechanical activation threshold. Furthermore, these responses can be blocked by pulp application of the P2X1,2/3,3 antagonist TNP-ATP and also attenuated by medullary application of TNP-ATP. These results suggest that activation of P2X1,2/3,3 receptors in orofacial tissues plays a critical role in producing central sensitization in medullary dorsal horn nociceptive neurons.