title: Long-term potentiation of neuronal excitation by neuron-glia interactions in the rat spinal dorsal horn.
abstract: By imaging neuronal excitation in rat spinal cord slices with a voltage-sensitive dye, we examined the role of glial cells in the P2X receptor agonist alphabeta-methylene ATP (alphabetameATP)-triggered long-term potentiation (LTP) in the dorsal horn. Bath application of alphabetameATP potentiated neuronal excitation in the superficial dorsal horn. The potentiation was inhibited in the presence of the P2X receptor antagonists TNP-ATP, PPADS and A-317491, and was not induced in slices taken from rats neonatally treated with capsaicin. These results suggest that alphabetameATP acts on P2X receptors, possibly P2X(3) and/or P2X(2/3), in capsaicin-sensitive primary afferent terminals. Furthermore, the potentiation was inhibited by treatment with the glial metabolism inhibitor monofluoroacetic acid. Results obtained with the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, and antibodies to TNF-alpha and IL-6, as well as by double immunolabelling of activated p38 MAPK with markers of astrocytes and microglia, demonstrated that alphabetameATP activated p38 MAPK in astrocytes, and that the presence of proinflammatory cytokines and p38 MAPK activation were necessary for the induction of alphabetameATP-triggered LTP. These findings indicate that glial cells contribute to the alphabetameATP-induced LTP, which might be part of a cellular mechanism for the induction of persistent pain.
authors.affiliation: Department of Human and Artificial Intelligence Systems, Graduate School of Engineering, and Research and Education Program for Life Science, University of Fukui, 3-9-1 Bunkyo, Fukui 910-8507, Japan. ikeda@synapse.his.fukui-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsuda
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Inoue
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Murase
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D016202:N-Methylaspartate; D000255:Adenosine Triphosphate; D048051:p38 Mitogen-Activated Protein Kinases; D002211:Capsaicin