title: Purinergic receptors are involved in tooth-pulp evoked nocifensive behavior and brainstem neuronal activity.
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.
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai Chiyoda-ku, Tokyo, 101-8310, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Adachi
authors.forename: Kohei
authors.initials: K
authors.lastname: Shimizu
authors.forename: James W
authors.initials: JW
authors.lastname: Hu
authors.forename: Ikuko
authors.initials: I
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Noriaki
authors.initials: N
authors.lastname: Koshikawa
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Sessle
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shinoda
authors.forename: Makiko
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Kuniya
authors.initials: K
authors.lastname: Honda
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D003782:Dental Pulp / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004576:Electromyography; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008963:Molar / Q000187:drug effects / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D058476:Receptors, Purinergic P2X2 / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one