Effect of knock down of spinal cord PSD-93/chapsin-110 on persistent pain induced by complete Freund's adjuvant and peripheral nerve injury
Effect of knock down of spinal cord PSD-93/chapsin-110 on persistent pain induced by complete Freund's adjuvant and peripheral nerve injury
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DOI：
10.1016/j.pain.2003.08.003
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发表时间：
2003-11-01
期刊：
影响因子：
7.4
通讯作者：
Tao, YX
中科院分区：
文献类型：
--
作者：
Zhang, BS;Tao, F;Tao, YX
PSD-93/chapsin-110是一种含有PDZ结构域的神经元蛋白，它与中枢神经系统突触上的n-甲基- d -天冬氨酸受体（NMDAR）结合并聚集。它还在NMDAR周围组装一组特定的信号蛋白，并通过NMDAR介导下游信号传导。因此。PSD-93/chapsin-110可能参与通过NMDAR激活引发的许多生理和病理生理活动。在本研究中，我们报道了在大鼠脊髓中，特别是在浅背角中检测到丰富的PSD-93/chapsin-110蛋白。大鼠鞘内注射PSD-93/chapsin-110反义寡核苷酸，每24次注射4天，不仅脊髓PSD-93/chapsin-110表达显著降低，而且在完全性弗氏佐剂引起的炎症性疼痛和周围神经损伤引起的神经性疼痛中，足部对热刺激和机械刺激的退缩反应也显著减少。相比之下，鞘内注射PSD-93/chapsin-110错义寡脱氧核苷酸的大鼠没有表现出这些变化。我们还发现PSD-93/chapsin-110反义寡脱氧核苷酸预处理没有改变正常大鼠的运动活性或对急性有害热刺激和机械刺激的反应。本研究结果表明，脊髓PSD-93/ chapin -110蛋白缺乏可显著减轻完全性弗氏佐剂或周围神经损伤引起的慢性疼痛的热痛觉和机械性痛觉过敏。提示脊髓PSD-93/chapsin-110可能参与了慢性疼痛的中枢机制。我们的工作可能为慢性疼痛的治疗提供一个新的靶点。(C) 2003国际疼痛研究协会。Elsevier B.V.版权所有。
PSD-93/chapsin-110 is a neuronal PDZ domain-containing protein that binds to and clusters the N-methyl-D-aspartate receptor (NMDAR) at synapses in the central nervous system. It also assembles a specific set of signaling proteins around the NMDAR and mediates downstream signaling by the NMDAR. Thus. PSD-93/chapsin-110 might be involved in many physiological and pathophysiological actions triggered via the activation of the NMDAR. In the current study, we report that abundant PSD-93/chapsin-110 protein was detected in rat spinal cord, particularly in the superficial dorsal horn. The rats injected intrathecally with PSD-93/chapsin-110 antisense oligodeoxynucleotide every 24 It for 4 days displayed not only a remarkable decrease in spinal cord PSD-93/chapsin-110 expression but also a significant reduction in the paw withdrawal responses to thermal and mechanical stimuli during complete Freund's adjuvant-induced inflammatory pain and peripheral nerve injury-induced neuropathic pain. In contrast, the rats injected intrathecally with PSD-93/chapsin-110 missense oligodeoxynucleotide did not exhibit these changes. We also found that pretreatment with PSD-93/chapsin-110 antisense oligodeoxynucleotide did not change the locomotor activity or the responses to acute noxious thermal and mechanical stimuli in intact rats. The present results indicate that the deficiency of spinal cord PSD-93/chapsin-110 protein significantly attenuates thermal and mechanical hyperalgesia in complete Freund's adjuvant- or peripheral nerve injury-induced chronic pain. This suggests that spinal cord PSD-93/chapsin-110 might be involved in the central mechanism of chronic pain. Our work might provide a new target for the therapy of chronic pain. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.