Evaluation of behavior and expression of NaV1.7 in dorsal root ganglia after sciatic nerve compression and application of nucleus pulposus in rats
Evaluation of behavior and expression of NaV1.7 in dorsal root ganglia after sciatic nerve compression and application of nucleus pulposus in rats
复制标题
DOI：
10.1007/s00586-013-3076-y
复制
发表时间：
2014-02-01
影响因子：
2.8
通讯作者：
Ohtori, Seiji
中科院分区：
文献类型：
--
作者：
Mukai, Michiaki;Sakuma, Yoshihiro;Ohtori, Seiji
腰椎间盘突出症引起的疼痛的病理机制尚未完全阐明。炎症部位产生的前列腺素和细胞因子会产生相关的疼痛；然而，非甾体抗炎药和类固醇有时对患者无效。河豚毒素敏感的电压门控钠 (NaV) 通道与初级感觉神经的感觉传递有关。钠通道 NaV1.7 已成为一个有吸引力的镇痛靶点。本研究的目的是评估大鼠坐骨神经压迫和髓核 (NP) 联合应用后疼痛相关行为和背根神经节 (DRG) 中 NaV1.7 的表达。将大鼠分为三组，分别使用镊子进行 NP 坐骨神经压迫 2 s (n = 20)、既不压迫也不使用 NP 的假手术 (n = 20) 或不进行手术（对照组，n = 20）。使用 von Frey 细丝在三周内每隔一天测量一次机械痛觉过敏。术后 7 天和 14 天使用免疫组织化学检查 L5 DRG 中 NaV1.7 的表达。比较三组间NaV1.7免疫反应的神经元数量。在14天的观察中，神经压迫加NP应用组发现机械性痛觉过敏，而假手术组和对照组未发现机械性痛觉过敏（P < 0.05）。与假手术组和对照大鼠相比，神经压迫加 NP 施用组 L5 DRG 中 NaV1.7 的表达上调（P < 0.01）。我们的结果表明神经压迫加 NP 施用会产生疼痛相关行为。我们得出的结论是，DRG 神经元中 NaV1.7 的表达可能在介导压缩损伤和暴露于 NP 后坐骨神经的疼痛中发挥重要作用。
The pathomechanisms of pain resulting from lumbar disc herniation have not been fully elucidated. Prostaglandins and cytokines generated at the inflammatory site produce associated pain; however, non-steroidal anti-inflammatory drugs and steroids are sometimes ineffective in patients. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are related to sensory transmission in primary sensory nerves. The sodium channel NaV1.7 has emerged as an attractive analgesic target. The purpose of this study was to evaluate pain-related behavior and expression of NaV1.7 in dorsal root ganglia (DRG) after combined sciatic nerve compression and nucleus pulposus (NP) application in rats.Rats were divided into three groups and underwent either sciatic nerve compression with NP for 2 s using forceps (n = 20), sham operation with neither compression nor NP (n = 20), or no operation (controls, n = 20). Mechanical hyperalgesia was measured every second day for three weeks using von Frey filaments. NaV1.7 expression in L5 DRG was examined 7 and 14 days after surgery using immunohistochemistry. The number of neurons immunoreactive for NaV1.7 was compared among the three groups.Mechanical hyperalgesia was found over the 14-day observation in the nerve compression plus NP application group, but not in the sham-operated or control groups (P < 0.05). NaV1.7 expression in L5 DRG was up-regulated in the nerve compression plus NP application group, compared with sham-operated and control rats (P < 0.01).Our results indicate that nerve compression plus NP application produces pain-related behavior. We conclude that NaV1.7 expression in DRG neurons may play an important role in mediating pain from sciatic nerves after compression injury and exposure to NP.