Nakae Aya, Nakai Kunihiro, Tanaka Tatsuya, Hagihira Saotoshi, Shibata Masahiko, Ueda Koichi, Masimo Takashi
Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita City, Osaka, Japan.
Eur J Neurosci. 2008 May;27(9):2373-9. doi: 10.1111/j.1460-9568.2008.06205.x.
We examined whether infraorbital nerve injury affected the RNA editing efficiency of the serotonin (5HT) 2C receptor in the cervical spinal cord, in association with increased pain thresholds, and whether a 5HT reuptake inhibitor (fluvoxamine; Depromel, Meiji Seika, Tokyo, Japan) altered this editing. Accordingly, we injured rats with an infraorbital nerve loose ligation and examined the pain thresholds, mRNA and mRNA editing of the 5HT2C receptor. We evaluated changes in mRNA editing and 5HT2C mRNA expression using cloning along with sequence analysis and quantitative reverse transcription-polymerase chain reaction to compare samples taken at post-injury day 28 from spinal cord sites, including the trigeminal nucleus caudalis, in naive, sham and injured rats (groups of each type had also received fluvoxamine). 5HT2C receptor expression was maintained post-injury. The RNA editing efficiency was statistically significantly lower at molecular sites A and B in ipsilateral spinal cord samples from injured rats than in bilateral samples from naive and sham rats, and in contralateral samples from injured rats. After injury, the proportional presence of two receptor isoforms changed, i.e. statistically significantly less VNV and significantly more INV and ISV. The proportions reverted after fluvoxamine administration. The post-injury change might be evidence of a functional adaptation mechanism that increases the expression of 5HT2C mRNA isoforms that encode receptors that are more sensitive to 5HT. This would activate the brainstem-spinal descending 5HT systems and, in effect, suppress nociceptive signals from primary afferent neurons to the spinal trigeminal nucleus caudalis.
我们研究了眶下神经损伤是否会影响颈脊髓中血清素（5HT）2C受体的RNA编辑效率，并与疼痛阈值升高相关，以及5HT再摄取抑制剂（氟伏沙明；Depromel，明治制果，东京，日本）是否会改变这种编辑。因此，我们对大鼠进行眶下神经松结扎损伤，并检测疼痛阈值、5HT2C受体的mRNA和mRNA编辑。我们使用克隆以及序列分析和定量逆转录-聚合酶链反应评估mRNA编辑和5HT2C mRNA表达的变化，以比较在损伤后第28天从脊髓部位（包括三叉神经尾侧核）采集的样本，这些样本来自未受伤、假手术和受伤的大鼠（每种类型的组也接受了氟伏沙明）。损伤后5HT2C受体表达得以维持。与未受伤和假手术大鼠的双侧样本以及受伤大鼠的对侧样本相比，受伤大鼠同侧脊髓样本中分子位点A和B处的RNA编辑效率在统计学上显著降低。损伤后，两种受体亚型的比例发生了变化，即VNV在统计学上显著减少，而INV和ISV显著增加。给予氟伏沙明后，这些比例恢复。损伤后的变化可能是一种功能适应机制的证据，该机制增加了编码对5HT更敏感的受体的5HT2C mRNA亚型的表达。这将激活脑干-脊髓下行5HT系统，实际上抑制从初级传入神经元到三叉神经脊髓尾侧核的伤害性信号。
