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大鼠坐骨神经压迫及应用髓核后背根神经节中NaV1.7的行为及表达评估

Evaluation of behavior and expression of NaV1.7 in dorsal root ganglia after sciatic nerve compression and application of nucleus pulposus in rats.

作者信息

Mukai Michiaki, Sakuma Yoshihiro, Suzuki Miyako, Orita Sumihisa, Yamauchi Kazuyo, Inoue Gen, Aoki Yasuchika, Ishikawa Tetsuhiro, Miyagi Masayuki, Kamoda Hiroto, Kubota Gou, Oikawa Yasuhiro, Inage Kazuhide, Sainoh Takeshi, Sato Jun, Nakamura Junichi, Takaso Masashi, Toyone Tomoaki, Takahashi Kazuhisa, Ohtori Seiji

机构信息

Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

出版信息

Eur Spine J. 2014 Feb;23(2):463-8. doi: 10.1007/s00586-013-3076-y. Epub 2013 Nov 20.

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

摘要

目的

腰椎间盘突出症所致疼痛的发病机制尚未完全阐明。炎症部位产生的前列腺素和细胞因子会引发相关疼痛;然而,非甾体抗炎药和类固醇药物有时对患者无效。河豚毒素敏感的电压门控钠(NaV)通道与初级感觉神经中的感觉传递有关。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受压并应用髓核(NP)后,背根神经节(DRG)中与疼痛相关的行为及NaV1.7的表达情况。

方法

将大鼠分为三组,分别接受以下处理:用镊子对坐骨神经进行2秒的压迫并应用NP(n = 20);既不进行压迫也不应用NP的假手术(n = 20);或不进行手术(对照组,n = 20)。每隔一天使用von Frey细丝测量机械性痛觉过敏,持续三周。术后7天和14天,采用免疫组织化学方法检测L5 DRG中NaV1.7的表达。比较三组中对NaV1.7呈免疫反应的神经元数量。

结果

在神经压迫加NP应用组的14天观察期内发现有机械性痛觉过敏,而假手术组和对照组未出现(P < 0.05)。与假手术组和对照组大鼠相比,神经压迫加NP应用组L5 DRG中NaV1.7的表达上调(P < 0.01)。

结论

我们的结果表明,神经压迫加NP应用会产生与疼痛相关的行为。我们得出结论,DRG神经元中NaV1.7的表达可能在介导压迫性损伤和暴露于NP后坐骨神经疼痛中起重要作用。

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