Zhang Wei, Shi Chang-Xi, Gu Xiao-ping, Ma Zheng-Liang, Zhu Wei
Department of Anesthesiology, Drum Tower Hospital, Medical Department of Nanjing University, Nanjing 210008, Jiangsu Province, China.
Anesth Analg. 2009 Mar;108(3):1015-20. doi: 10.1213/ane.0b013e318193ffd2.
Spinal N-methyl D-aspartate receptors play an important role in the pathogenesis of neuropathic pain, and administration of N-methyl D-aspartate receptor antagonists can attenuate this hyperpathia. Ifenprodil is an antagonist selective for N-methyl D-aspartate receptor 2B (NR2B) subunits. Several researches have reported effective analgesia of ifenprodil in animal models of neuropathic pain. We extended this work to include chronic compression of the dorsal root ganglia (CCD).
The paw withdrawal mechanical threshold and paw withdrawal thermal latency tests were used to assess mechanical allodynia and thermal hyperalgesia after a CCD operation and intrathecal injection of ifenprodil. We used immunohistochemistry and immunoblotting to investigate the effect of ifenprodil on NR2B subunits expression in CCD rats.
The data revealed increased expression of NR2B subunits in the superficial dorsal horn in CCD rats. We found that, in addition to a marked suppression of thermal hyperalgesia and mechanical allodynia, intrathecal injection ifenprodil treatment causes a decreased expression of NR2B in the spinal cord.
These data suggest that ifenprodil induced antinociception in CCD rats and provided further evidence for the important role of NR2B subunits in the development of neuropathic pain.
脊髓N-甲基-D-天冬氨酸受体在神经性疼痛的发病机制中起重要作用，给予N-甲基-D-天冬氨酸受体拮抗剂可减轻这种痛觉过敏。艾芬地尔是一种对N-甲基-D-天冬氨酸受体2B（NR2B）亚基具有选择性的拮抗剂。多项研究报道了艾芬地尔在神经性疼痛动物模型中的有效镇痛作用。我们将这项工作扩展到包括背根神经节慢性压迫（CCD）。
采用 paw withdrawal mechanical threshold（爪部撤离机械阈值）和 paw withdrawal thermal latency tests（爪部撤离热潜伏期试验）来评估CCD手术和鞘内注射艾芬地尔后的机械性异常性疼痛和热痛觉过敏。我们使用免疫组织化学和免疫印迹法来研究艾芬地尔对CCD大鼠NR2B亚基表达的影响。
数据显示CCD大鼠浅表背角中NR2B亚基的表达增加。我们发现，除了显著抑制热痛觉过敏和机械性异常性疼痛外，鞘内注射艾芬地尔治疗还会导致脊髓中NR2B的表达降低。
这些数据表明艾芬地尔在CCD大鼠中诱导了抗伤害感受，并为NR2B亚基在神经性疼痛发展中的重要作用提供了进一步的证据。
