Alleviating neuropathic pain mechanical allodynia by increasing Cdh1 in the anterior cingulate cortex

Molecular Pain

Chang Zhu¹  Chuan-Han Zhang¹  Li Wan¹  You-You Lv¹  Rong Hu¹  Wen-Long Yao¹  Wei Tan¹ 

[1] Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

关键词: Anterior cingulate cortex;    Neuropathic pain;    Mechanical allodynia;    Synaptic plasticity;    Cdh1;    Anaphase-promoting complex;   

Others  :  1228795
DOI  :  10.1186/s12990-015-0058-6

 received in 2015-01-12, accepted in 2015-08-26,  发布年份 2015

【 摘 要 】

Background

Plastic changes in the anterior cingulate cortex (ACC) are critical in the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. Cdh1, a co-activator subunit of anaphase-promoting complex/cyclosome (APC/C) regulates synaptic differentiation and transmission. Based on this, we hypothesised that the APC/C–Cdh1 played an important role in long-term plastic changes induced by neuropathic pain in ACC.

Results

We employed spared nerve injury (SNI) model in rat and found Cdh1 protein level in the ACC was down-regulated 3, 7 and 14 days after SNI surgery. We detected increase in c-Fos expression, numerical increase of organelles, swollen myelinated fibre and axon collapse of neuronal cells in the ACC of SNI rat. Additionally, AMPA receptor GluR1 subunit protein level was up-regulated on the membrane through a pathway that involves EphA4 mediated by APC/C–Cdh1, 3 and 7 days after SNI surgery. To confirm the effect of Cdh1 in neuropathic pain, Cdh1-expressing lentivirus was injected into the ACC of SNI rat. Intra-ACC treatment with Cdh1-expressing lentivirus vectors elevated Cdh1 levels, erased synaptic strengthening, as well as alleviating established mechanical allodynia in SNI rats. We also found Cdh1-expressing lentivirus normalised SNI-induced redistribution of AMPA receptor GluR1 subunit in ACC by regulating AMPA receptor trafficking.

Conclusions

These results provide evidence that Cdh1 in ACC synapses may offer a novel therapeutic strategy for treating chronic neuropathic pain.

【 授权许可】

   
2015 Tan et al.

【 图 表 】

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