title: Alleviating neuropathic pain mechanical allodynia by increasing Cdh1 in the anterior cingulate cortex.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. kimeru0228@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. wlyao82@126.com.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. hurong1109@gmail.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. youyouwulv@163.com.
authors.forename: You-You
authors.initials: YY
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. wanli0604@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. chuanhan_zhang@163.com.
authors.forename: Chuan-Han
authors.initials: CH
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. zhchag@gmail.com.
authors.forename: Chang
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000818:Animals; D064200:Cdh1 Proteins / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000648:ultrastructure; D006930:Hyperalgesia / Q000150:complications / Q000378:metabolism*; D016086:Lentivirus / Q000378:metabolism; D008297:Male; D008845:Microinjections; D009437:Neuralgia / Q000150:complications / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D036122:Receptor, EphA4 / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D064200:Cdh1 Proteins; D021122:Protein Subunits; D016760:Proto-Oncogene Proteins c-fos; D036122:Receptor, EphA4; D018091:Receptors, AMPA