Wu Feixiang, Pan Ruirui, Chen Jiaying, Sugita Megumi, Chen Caiyang, Tao Yong, Yu Weifeng, Sun Yuming
Department of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, China.
Department of Anesthesiology and Critical Care, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA.
Biomed Res Int. 2014;2014:871637. doi: 10.1155/2014/871637. Epub 2014 Aug 28.
Although neuropathic pain (NP) is still not fully understood by scientists and clinicians alike, studies suggest that N-methyl-D-aspartate (NMDA) receptors play an important role in the induction and maintenance of NP. A promising treatment for NP is through the downregulation of NMDA subunit GluN2B by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for NP, Lv-siGluN2B (lentivirus carrying siRNA targeting GluN2B subunit) was prepared and the antinociception effects were observed in chronic constriction injury (CCI) rats in the present study. Results showed that Lv-siGluN2B was transduced into spinal cord cells after intrathecal injections and effectively reduced the nociception induced by sciatic nerve ligation while inhibiting the mRNA and protein expression of GluN2B. This antinociception effect lasted approximately 7 weeks. These findings suggest that GluN2B subunit could be a target for NP treatment and Lv-siGluN2B represents a new potential option for long-term treatment of NP.
尽管科学家和临床医生对神经性疼痛（NP）仍未完全了解，但研究表明，N-甲基-D-天冬氨酸（NMDA）受体在NP的诱发和维持中起重要作用。一种有前景的NP治疗方法是通过RNA干扰下调NMDA亚基GluN2B；然而，裸小干扰RNA（siRNA）在长期治疗中无效。为了配制一种可行的NP长期治疗方法，本研究制备了Lv-siGluN2B（携带靶向GluN2B亚基的siRNA的慢病毒），并在慢性压迫损伤（CCI）大鼠中观察其镇痛效果。结果显示，鞘内注射后，Lv-siGluN2B被转导至脊髓细胞，有效减轻坐骨神经结扎诱导的痛觉过敏，同时抑制GluN2B的mRNA和蛋白表达。这种镇痛作用持续约7周。这些发现表明，GluN2B亚基可能是NP治疗的一个靶点，Lv-siGluN2B代表了NP长期治疗的一种新的潜在选择。
