Zhang Bosheng, Tao Feng, Liaw Wen-Jinn, Bredt David S, Johns Roger A, Tao Yuan-Xiang
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 355 Ross, 720 Rutland Ave., Baltimore, MD 21205, USA.
Pain. 2003 Nov;106(1-2):187-96. doi: 10.1016/j.pain.2003.08.003.
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 h 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.
PSD - 93/Chapsin - 110是一种含有神经元PDZ结构域的蛋白质，它能与N - 甲基 - D - 天冬氨酸受体（NMDAR）结合并使其在中枢神经系统的突触处聚集。它还能在NMDAR周围组装一组特定的信号蛋白，并介导NMDAR的下游信号传导。因此，PSD - 93/Chapsin - 110可能参与了许多通过NMDAR激活引发的生理和病理生理作用。在本研究中，我们报告在大鼠脊髓中检测到大量的PSD - 93/Chapsin - 110蛋白，尤其是在脊髓背角浅层。每24小时鞘内注射PSD - 93/Chapsin - 110反义寡脱氧核苷酸，持续4天的大鼠不仅脊髓中PSD - 93/Chapsin - 110表达显著降低，而且在完全弗氏佐剂诱导的炎性疼痛和周围神经损伤诱导的神经性疼痛期间，对热和机械刺激的爪部退缩反应也显著降低。相比之下，鞘内注射PSD - 93/Chapsin - 110错义寡脱氧核苷酸的大鼠未表现出这些变化。我们还发现，用PSD - 93/Chapsin - 110反义寡脱氧核苷酸预处理不会改变完整大鼠的运动活性或对急性有害热和机械刺激的反应。目前的结果表明，脊髓PSD - 93/Chapsin - 110蛋白的缺乏显著减轻了完全弗氏佐剂或周围神经损伤诱导的慢性疼痛中的热和机械性痛觉过敏。这表明脊髓PSD - 93/Chapsin - 110可能参与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靶点。
