Department of Anesthesiology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Anesthesiology. 2010 Jun;112(6):1482-93. doi: 10.1097/ALN.0b013e3181d69494.
Spinal N-methyl-D-aspartate receptors have been demonstrated to play an important role in the facilitation and maintenance of nociception. To avoid adverse effects of blocking N-methyl-D-aspartate receptors in the central nervous system, blocking N-methyl-D-aspartate receptor in peripheral nervous system is an ideal alternative. Transfection of small interfering RNAs (siRNAs) into cells has been revealed to provide potent silencing of specific genes. In this study, the authors examined the effect of subcutaneous injection of siRNA targeting the NR1 subunit of the N-methyl-D-aspartate receptor on silencing NR1 gene expression and subsequently abolishing inflammatory nociception in rats.
Male Sprague-Dawley rats received intradermal injection of NR1 siRNA and underwent injection of formalin or complete Freund's adjuvant. The flinch response and mechanical hypersensitivity by von Frey filaments were assessed. Then the messenger RNA and protein of NR1 in skin and dorsal root ganglion were analyzed.
The results revealed that subcutaneous injection of 1 nmol NR1 siRNA effectively diminished the nociception induced by formalin and complete Freund's adjuvant stimuli and attenuated the level of NR1 messenger RNA and protein in skin and ipsilateral dorsal root ganglion. The antinociception effect and the inhibition of NR1 expression persisted for about 7 days after administration of NR1 siRNA.
The data of this study suggest that NR1 siRNA has potential therapeutic value in the treatment of inflammatory pain induced or maintained by peripheral nociceptor activity and support the potential application of this method to the study of nociceptive processes and target the validation of pain-associated genes.
脊髓 N-甲基-D-天冬氨酸受体在促进和维持伤害感受中发挥重要作用。为避免阻断中枢神经系统中 N-甲基-D-天冬氨酸受体的不良反应，阻断周围神经系统中的 N-甲基-D-天冬氨酸受体是一种理想的替代方法。转染小干扰 RNA（siRNA）已被证明可有效沉默特定基因。在这项研究中，作者研究了靶向 N-甲基-D-天冬氨酸受体 NR1 亚基的 siRNA 经皮下注射对沉默 NR1 基因表达以及随后在大鼠中消除炎症性伤害感受的影响。
雄性 Sprague-Dawley 大鼠接受 NR1 siRNA 皮内注射，并接受福尔马林或完全弗氏佐剂注射。评估缩腿反应和 von Frey 细丝引起的机械性超敏反应。然后分析皮肤和背根神经节中 NR1 的信使 RNA 和蛋白质。
结果表明，皮下注射 1 nmol NR1 siRNA 可有效减轻福尔马林和完全弗氏佐剂刺激引起的伤害感受，并减弱皮肤和同侧背根神经节中 NR1 信使 RNA 和蛋白质的水平。NR1 siRNA 给药后约 7 天，镇痛作用和 NR1 表达抑制持续存在。
本研究数据表明，NR1 siRNA 在治疗由周围伤害感受器活性引起或维持的炎症性疼痛方面具有潜在的治疗价值，并支持将该方法应用于伤害感受过程的研究和疼痛相关基因的验证。
