Antisense oligonucleotides to N-methyl-D-aspartate receptor subunits attenuate formalin-induced nociception in the rat.
Antisense oligonucleotides to N-methyl-D-aspartate receptor subunits attenuate formalin-induced nociception in the rat.
复制标题
N-甲基-D-天冬氨酸受体亚基的反义寡核苷酸可减弱福尔马林诱导的大鼠伤害感受。
DOI：
10.1016/s0006-8993(02)02243-6
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发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
Crosby,Gregory
中科院分区：
文献类型：
--
作者：
Yukhananov,Rus;Guan,Jane;Crosby,Gregory
Noxious peripheral stimuli increase the sensitivity of central nociceptive neurons to subsequent noxious stimuli. This occurs in part through activation of spinal N-methyl-d-aspartate (NMDA) receptors. These receptors are heteromeric complexes of NMDA-R1 and NMDA-R2 A–D subunits. NMDA-R1 is necessary for the formation of functional NMDA receptors whereas the R2 subunits (A–D) modify the properties of the receptor. However, the role of the various receptor subtypes in nociception has not been established. In this study, we used intrathecally administered phosphodiester antisense oligonucleotides (ODEs) to examine the role of the NMDA-R1, NMDA-R2C and NMDA-R2D subunits in the mediation of formalin-induced nociception in the rat. The antisense ODEs against the NMDA-R1 and NMDAR-2C subunits reduced nociceptive behaviors whereas the corresponding sense ODEs had no effect. In contrast, nociception was unaffected by the antisense ODE to NMDAR-2D. Using an RNase protection assay, we also found that each antisense ODE selectively decreased the level of the corresponding mRNA in the lumbar spinal cord but that the sense ODEs had no such effect. Accordingly, these data provide evidence that the R1 and R2C subunits, but not R2D, of the NMDA receptor participate in the development of formalin-induced nociception.
