The role of N-methyl-d-aspartate receptor subunits in the rat thalamic mediodorsal nucleus during central sensitization
The role of N-methyl-d-aspartate receptor subunits in the rat thalamic mediodorsal nucleus during central sensitization
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DOI：
10.1016/j.brainres.2010.11.054
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发表时间：
2011-01
期刊：
影响因子：
2.9
通讯作者：
Mitsuhiro Kaneko;T. Kaneko;R. Kaneko;Uraiwan Chokechanachaisakul;J. Kawamura;M. Sunakawa;T. Okiji;H. Suda
中科院分区：
文献类型：
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作者：
Mitsuhiro Kaneko;T. Kaneko;R. Kaneko;Uraiwan Chokechanachaisakul;J. Kawamura;M. Sunakawa;T. Okiji;H. Suda
我们在大鼠丘脑内侧核 (MD) 中鉴定出了牙髓驱动神经元 (TPDN)，并表明，异硫氰酸烯丙酯（芥子油）对磨牙牙髓的化学调理刺激可增加 TPDN 在 MD 中的反应性。本研究的目的是探讨将芥子油涂抹到大鼠牙髓后，N-甲基-d-天冬氨酸受体（NMDA 受体）在致敏中枢神经系统中的作用。将 MK-801（一种非竞争性 NMDA 受体拮抗剂）显微注射到丘脑 MD 核中，会降低丘脑 MD 核中 TPDN 的反应性。基因表达分析表明，芥子油的应用增加了丘脑中 NMDA 受体亚基 NR2A 和 NR2D mRNA 的表达水平，而 MK-801 则降低了这种增加。当 MK801 显微注射后全身给予纳洛酮（一种阿片受体拮抗剂）时，TPDN 的反应性重新点燃，NR2D 和 NR2A mRNA 的表达水平增加。此外，利多卡因预处理消除了芥子油诱导的 NR2D 和 NR2A mRNA 上调。这些结果表明，在中枢敏化过程中，NMDA 受体和内源性阿片类药物相关抑制机制的相互作用在丘脑 MD 核中 TPDN 反应性的改变中发挥着关键作用。
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.