1. Academic Validation
  2. PSD-95 in the anterior cingulate cortex contributes to neuropathic pain by interdependent activation with NR2B

PSD-95 in the anterior cingulate cortex contributes to neuropathic pain by interdependent activation with NR2B

  • Sci Rep. 2022 Oct 12;12(1):17114. doi: 10.1038/s41598-022-21488-7.
Ang Li # 1 Chang-Jun Huang # 1 2 Kai-Peng Gu 1 Yan Huang 1 Ya-Qin Huang 1 Hui Zhang 1 Jia-Piao Lin 1 Yu-Fan Liu 1 Yan Yang 3 Yong-Xing Yao 4
Affiliations

Affiliations

  • 1 Department of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
  • 2 Department of Anesthesia, First People's Hospital of Linping District, Hangzhou, China.
  • 3 Department of Neurobiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Department of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China. yaoyongxing@zju.edu.cn.
  • # Contributed equally.
Abstract

Studies suggest that the scaffolding protein, postsynaptic density protein-95 (PSD-95), is involved in multiple neurological dysfunctions. However, the role of PSD-95 in the anterior cingulate cortex (ACC) in neuropathic pain (NP) has not been investigated. The current study addressed the role of PSD-95 in the ACC in NP and its modulating profile with NMDA Receptor subunit 2B (NR2B). The NP model was established by chronic constriction injury (CCI) of the sciatic nerve, and mechanical and thermal tests were used to evaluate behavioral hyperalgesia. Protein expression and distribution were evaluated using immunohistochemistry and western blotting. The results showed that PSD-95 and NR2B were co-localized in neurons in the ACC. After CCI, both PSD-95 and NR2B were upregulated in the ACC. Inhibiting NR2B with Ro 25-6981 attenuated pain hypersensitivity and decreased the over-expression of PSD-95 induced by CCI. Furthermore, intra-ACC administration of PSD-95 antisense oligonucleotide not only attenuated pain hypersensitivity but also downregulated the NR2B level and the phosphorylation of cyclic AMP response element-binding protein. These results demonstrated that PSD-95 in the ACC contributes to NP by interdependent activation of NR2B.

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