Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain
Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain
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含有 NR2B 的脊髓 NMDA 受体在神经性疼痛发生中的作用
DOI：
10.1016/j.expneurol.2008.10.018
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发表时间：
2009-02-01
影响因子：
5.3
通讯作者：
Xing, Guo-Gang
中科院分区：
文献类型：
--
作者：
Qu, Xiao-Xiu;Cai, Jie;Xing, Guo-Gang
在慢性疼痛中，脊髓背角的N-甲基-D-天冬氨酸（NMDA）受体的激活已被证明是启动中枢敏感化和背角神经元过度兴奋所必需的。然而，脊髓中含有NR 2B的NMDA（NMDA-2B）受体是否参与其中仍不清楚。采用L5脊神经结扎（SNL）大鼠的行为学测试和在体细胞外电生理记录，研究脊髓NMDA-2B受体在神经病理性疼痛发生中的作用。我们的研究表明，鞘内（i.t.）注射选择性NMDA-2B受体拮抗剂Ro 25-6981具有剂量依赖性抗异常性疼痛作用，但不引起运动功能障碍。此外，I.T.在SNL之前应用另一种NMDA-2B受体拮抗剂ifenprodil也显著抑制机械异常性疼痛，但不抑制热痛觉过敏。这些数据表明，脊髓水平的NMDA-2B受体在神经病理性疼痛的发展中起重要作用，特别是在神经损伤后的早期阶段。此外，Ro 25-6981脊髓给药不仅对正常和SNL大鼠背角宽动态范围（WDR）神经元的C纤维反应具有剂量依赖性抑制作用，而且还显著抑制了坐骨神经高频刺激（HFS）诱导的WDR神经元C纤维反应的长时程增强（LTP）。这些结果表明，背角NMDA-2B受体的激活可能是至关重要的脊髓伤害性突触传递和神经损伤后持久的脊髓过度兴奋的发展。总之，脊髓NMDA-2B受体通过诱导背角伤害性突触传递中的LTP在中枢敏化和神经病理性疼痛的发展中发挥作用。因此，脊髓NMDA-2B受体可能成为临床疼痛治疗的靶点。(c)2008年爱思唯尔公司All rights reserved.
Activation of N-methyl-D-aspartate (NMDA) receptors in the spinal dorsal horn has been shown to be essential for the initiation of central sensitization and the hyperexcitability of dorsal horn neurons in chronic pain. However, whether the spinal NR2B-containing NMDA (NMDA-2B) receptors are involved still remains largely unclear. Using behavioral test and in vivo extracellular electrophysiological recording in L5 spinal nerve-ligated (SNL) neuropathic rats, we investigate the roles of spinal cord NMDA-2B receptors in the development of neuropathic pain. Our study showed that intrathecal (i.t.) injection of Ro 25-6981, a selective NMDA-2B receptor antagonist, had a dose-dependent anti-allodynic effect without causing motor dysfunction. Furthermore, i.t. application of another NMDA-2B receptor antagonist ifenprodil prior to SNL also significantly inhibited the mechanical allodynia but not the thermal hyperalgesia. These data suggest that NMDA-2B receptors at the spinal cord level play an important role in the development of neuropathic pain, especially at the early stage following nerve injury. In addition, spinal administration of Ro 25-6981 not only had a dose-dependent inhibitory effect on the C-fiber responses of dorsal horn wide dynamic range (WDR) neurons in both normal and SNL rats, but also significantly inhibited the long-term potentiation (LTP) in the C-fiber responses of WDR neurons induced by high-frequency stimulation (HFS) applied to the sciatic nerve. These results indicate that activation of the dorsal horn NMDA-2B receptors may be crucial for the spinal nociceptive synaptic transmission and for the development of long-lasting spinal hyperexcitability following nerve injury. In conclusion, the spinal cord NMDA-2B receptors play a role in the development of central sensitization and neuropathic pain via the induction of LTP in dorsal horn nociceptive synaptic transmission. Therefore, the spinal cord NMDA-2B receptor is likely to be a target for clinical pain therapy. (c) 2008 Elsevier Inc. All rights reserved.