Purinergic receptors are involved in tooth-pulp evoked nocifensive behavior and brainstem neuronal activity

BACKGROUND: To evaluate whether P2X receptors are involved in responses to noxious pulp stimulation, the P2X(3 )and P2X(2/3 )receptor agonist α,β-methyleneATP (α,β-meATP) was applied to the molar tooth pulp and nocifensive behavior and extracellular-signal regulated kinase (ERK) phosphorylation in trigeminal spinal subnucleus caudalis (Vc), trigeminal spinal subnucleus interpolaris (Vi), upper cervical spinal cord (C1/C2) and paratrigeminal nucleus (Pa5) neurons were analyzed in rats. RESULTS: Genioglossus (GG) muscle activity was evoked by pulpal application of 100 mM α,β-meATP and was significantly larger than GG activity following vehicle (phosphate-buffered saline PBS) application (p < 0.01). The enhanced GG muscle activity following 100 mM α,β-meATP was significantly reduced (p < 0.05) by co-application of 1 mM TNP-ATP (P2X(1), P2X(3 )and, P2X(2/3 )antagonist). A large number of pERK-LI cells were expressed in the Vc, Vi/Vc, C1/C2 and Pa5 at 5 min following pulpal application of 100 mM α,β-meATP compared to PBS application to the pulp (p < 0.05). The pERK-LI cell expression and GG muscle activity induced by 100 mM α,β-meATP pulpal application were significantly reduced after intrathecal injection of the MAPK/ERK kinase (MEK) inhibitor PD 98059 and by pulpal co-application of 1 mM TNP-ATP (p < 0.05). CONCLUSIONS: The present findings suggest that activation of P2X(3 )and P2X(2/3 )receptors in the tooth pulp is sufficient to elicit nociceptive behavioral responses and trigeminal brainstem neuronal activity.