The role of N-methyl-D-aspartate receptor subunits in the rat thalamic mediodorsal nucleus during central sensitization.
We have identified tooth pulp-driven neurons (TPDNs) in the thalamic mediodorsal nucleus (MD) in rats and showed that the TPDNs' responsiveness in the MD is increased by chemical conditioning stimulation of allyl-isothiocyanate (mustard oil) to the molar tooth pulp. The aim of the present study was to address the role of N-methyl-d-aspartate receptors (NMDA receptors) in the sensitized central nervous system following the mustard oil application to the rat tooth pulp. Microinjection of MK-801, a noncompetitive NMDA receptor antagonist, to the thalamic MD nucleus reduced the TPDNs' responsiveness in the thalamic MD nucleus. Gene expression analysis showed that expression levels of NMDA receptor subunits NR2A and NR2D mRNAs in the thalamus were increased by the mustard oil application and that the increases were reduced by MK-801. When naloxone, an opioid receptor antagonist, was given systemically following the MK801 microinjection, the TPDNs' responsiveness was rekindled and expression levels of NR2D and NR2A mRNAs were increased. Moreover, lidocaine pretreatment abolished the mustard oil-induced upregulation of NR2D and NR2A mRNAs. These results suggest that, during central sensitization, interaction of NMDA receptors and endogeneous opioid-related inhibitory mechanisms plays critical role in the alteration of the TPDNs' responsiveness in the thalamic MD nucleus.
Pulp Biology and Endodontics, Department of Restorative Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Mitsuhiro
M
Kaneko
Tomoatsu
T
Kaneko
Reika
R
Kaneko
Uraiwan
U
Chokechanachaisakul
Jun
J
Kawamura
Mitsuhiro
M
Sunakawa
Takashi
T
Okiji
Hideaki
H
Suda
D000344:Afferent Pathways / Q000503:physiopathology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D003782:Dental Pulp / Q000294:innervation*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D004525:Efferent Pathways / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007509:Irritants / Q000494:pharmacology / Q000633:toxicity; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008963:Molar / Q000294:innervation; D009149:Mustard Plant / Q000633:toxicity; D009270:Naloxone / Q000494:pharmacology / Q000633:toxicity; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000633:toxicity; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010938:Plant Oils / Q000494:pharmacology / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology*; D014098:Toothache / Q000139:chemically induced / Q000503:physiopathology*
D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D007509:Irritants; C120997:NR2A NMDA receptor; C464436:NR2D NMDA receptor; D009292:Narcotic Antagonists; D010938:Plant Oils; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D009270:Naloxone; D016291:Dizocilpine Maleate; D008012:Lidocaine; C027793:mustard oil