N-methyl D-aspartate receptor subtype 2B antagonist, Ro 25-6981, attenuates neuropathic pain by inhibiting postsynaptic density 95 expression

作者：Huang, Ling-Er; Guo, Shao-Hui; Thitiseranee, Lalita; Yang, Yan; Zhou, Yan-Feng; Yao, Yong-Xing^*

来源：Scientific Reports, 2018, 8(1): 7848.

DOI：10.1038/s41598-018-26209-7

• PERIPHERAL-NERVE INJURY
• BONE CANCER PAIN
• INFLAMMATORY PAIN
• NMDA RECEPTOR
• NR2B SUBUNIT
• SPINAL-CORD
• THERMAL HYPERALGESIA
• PHOSPHORYLATION
• ACTIVATION
• MAINTENANCE

Postsynaptic density-95 (PSD-95) is a synaptic scaffolding protein that plays a crucial role in the development of neuropathic pain. However, the underlying mechanism remains unclear. To address the role of PSD-95 in N-methyl-D-aspartate receptor subtype 2B (NR2B)-mediated chronic pain, we investigated the relationship between PSD-95 activation and NR2B function in the spinal cord, by using a rat model of sciatic nerve chronic constriction injury (CCI). We demonstrate that the expression levels of total PSD-95 and cAMP response element binding protein (CREB), as well as phosphorylated NR2B, PSD-95, and CREB, in the spinal dorsal horn, and the interaction of NR2B with PSD-95 were increased in the CCI animals. Intrathecal injection of the selective NR2B antagonist Ro 25-6981 increased paw withdrawal latency, in a thermal pain assessment test. Moreover, repeated treatment with Ro 25-6981 markedly attenuated the thermal hypersensitivity, and inhibited the CCI-induced upregulation of PSD-95 in the spinal dorsal horn. Furthermore, intrathecal injection of the PSD-95 inhibitor strikingly reversed the thermal and mechanical hyperalgesia. Our results suggest that blocking of NR2B signaling in the spinal cord could be used as a therapeutic candidate for treating neuropathic pain.

• 出版日期2018-5-18
• 单位浙江大学