1. Alleviating neuropathic pain mechanical allodynia by increasing Cdh1 in the anterior cingulate cortex.
- Author
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Tan W, Yao WL, Hu R, Lv YY, Wan L, Zhang CH, and Zhu C
- Subjects
- Animals, Gyrus Cinguli ultrastructure, Hyperalgesia complications, Lentivirus metabolism, Male, Microinjections, Neuralgia complications, Protein Subunits metabolism, Proto-Oncogene Proteins c-fos metabolism, Rats, Sprague-Dawley, Receptor, EphA4 metabolism, Receptors, AMPA metabolism, Recombination, Genetic genetics, Signal Transduction, Synapses metabolism, Synapses ultrastructure, Cdh1 Proteins metabolism, Gyrus Cinguli metabolism, Hyperalgesia metabolism, Neuralgia metabolism
- 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.
- Published
- 2015
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