中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (3): 464-469.doi: 10.4103/1673-5374.202925

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

雌激素抑制坐骨神经病理性疼痛：与脊髓背根神经节N-甲基-D-天门冬氨酸受体1的表达上调有关?

  

  • 收稿日期:2017-01-09 出版日期:2017-03-15 发布日期:2017-03-15
  • 基金资助:

    石河子大学应用基础研究青年项目（2015zrkyq-lh19）

Estrogen affects neuropathic pain through upregulating N-methyl-D-aspartate acid receptor 1 expression in the dorsal root ganglion of rats

Chao Deng1, Ya-juan Gu2, Hong Zhang1, Jun Zhang3   

  1. 1 Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region, China;2 Department of Obstetrics and Gynecology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region, China 3 Department of Genetics, School of Medicine, Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region, China
  • Received:2017-01-09 Online:2017-03-15 Published:2017-03-15
  • Contact: Chao Deng,1452793572@qq.com.
  • Supported by:

    This research was supported by the Youth Shihezi University Applied Basic Research Project of China, No. 2015ZRKYQ-LH19.

PDF

363

摘要：

有研究显示，雌激素可影响神经病理性疼痛的产生和传递，具体调节机制尚不清楚，也有人提出，N-甲基-D-天门冬氨酸受体1的激活在痛觉过敏以及异常痛的产生和维持中发挥着重要的作用。为验证雌激素与周围神经疼痛之间的关系，实验设计了建立坐骨神经慢性压榨损伤大鼠模型，于颈后皮下注射17β-雌二醇和或N-甲基-D-天门冬氨酸受体1阻断剂AP-5，1次/d，连续15 d。发现注射雌激素的坐骨神经损伤大鼠机械刺激缩足反射阈值降低热刺激缩足反射潜伏期缩短，脊髓背根神经节N-甲基-D-天门冬氨酸受体1蛋白表达和免疫反应均增加，而AP-5组和雌激素+AP-5联合应用组上述指标无明显变化。说明雌激素可显著降低坐骨神经慢性压榨损伤模型大鼠的痛域值，脊髓背根神经节N-甲基-D-天门冬氨酸受体1的表达上调是其作用途径。

ORCID:0000-0002-5216-6008(Chao Deng)

关键词: 神经再生, 周围神经损伤, 雌激素, 17&beta, -雌二醇, N-甲基-D-天门冬氨酸受体1, 疼痛, 坐骨神经, 慢性压榨损伤, 神经病理性疼痛, AP-5, 背根神经节, 脊髓

Abstract:

Estrogen affects the generation and transmission of neuropathic pain, but the specific regulatory mechanism is still unclear. Activation of the N-methyl-D-aspartate acid receptor 1 (NMDAR1) plays an important role in the production and maintenance of hyperalgesia and allodynia. The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain. A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats. These rats were then subcutaneously injected with 17β-estradiol, the NMDAR1 antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP-5), or both once daily for 15 days. Compared with injured drug naïve rats, rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency, indicating increased sensitivity to mechanical and thermal pain. Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity (as assessed by immunohistochemistry) and protein (as determined by western blot assay) in spinal dorsal root ganglia. This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5, whereas AP-5 alone did not affect NMDAR1 expression. These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve, and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.

Key words: nerve regeneration, peripheral nerve injury, estrogen, 17β-estradiol, N-methyl-D-aspartic acid receptor 1, pain, sciatic nerve, chronic constriction injury, neuropathic pain, D(-)-2-amino-5-phosphonopentanoic acid, dorsal root ganglion, spinal cord, immunoreactivity, western blot assay, neural regeneration