Open Access Research

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

Kazunori Adachi123, Kohei Shimizu4, James W Hu5, Ikuko Suzuki6, Hiroshi Sakagami1, Noriaki Koshikawa23, Barry J Sessle5, Masamichi Shinoda67, Makiko Miyamoto68, Kuniya Honda69 and Koichi Iwata67*

Author Affiliations

1 Department of Diagnostic & Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyaki-dai, Sakado, 350-0283, Japan

2 Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai Chiyoda-ku, Tokyo, 101-8310, Japan

3 Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai Chiyoda-ku, Tokyo, 101-8310, Japan

4 Department of Endodontics, Nihon University School of Dentistry, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai Chiyoda-ku, Tokyo, 101-8310, Japan

5 Department of Oral Physiology, Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, M5G 1G6, Canada

6 Department of Physiology, Nihon University School of Dentistry, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai Chiyoda-ku, Tokyo, 101-8310, Japan

7 Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai Chiyoda-ku, Tokyo, 101-8310, Japan

8 Department of Anesthesiology, Nihon University School of Dentistry, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai Chiyoda-ku, Tokyo, 101-8310, Japan

9 Oral and Maxillofacial Surgery Nihon University School of Dentistry, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai Chiyoda-ku, Tokyo, 101-8310, Japan

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Molecular Pain 2010, 6:59  doi:10.1186/1744-8069-6-59

Published: 22 September 2010

Abstract

Background

To evaluate whether P2X receptors are involved in responses to noxious pulp stimulation, the P2X3 and P2X2/3 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 (P2X1, P2X3 and, P2X2/3 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 P2X3 and P2X2/3 receptors in the tooth pulp is sufficient to elicit nociceptive behavioral responses and trigeminal brainstem neuronal activity.