Rapid Turnover of Cortical NCAM1 Regulates Synaptic Reorganization after Peripheral Nerve Injury

Cell Rep. 2018 Jan 16;22(3):748-759. doi: 10.1016/j.celrep.2017.12.059.


Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC) induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization. We show striking parallels in the underlying mechanism with the maintenance of NMDA-receptor- and protein-synthesis-dependent long-term potentiation (LTP) in the ACC. Our results, therefore, demonstrate a synaptic mechanism for cortical reorganization and suggest potential avenues for neuropathic pain treatment.

Keywords: NCAM1; neural cell adhesion molecule 1; neuropathic pain; protein turnover; synaptic reorganization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD56 Antigen / metabolism*
  • Gyrus Cinguli / metabolism*
  • Gyrus Cinguli / pathology
  • Male
  • Mice
  • Peripheral Nerve Injuries / metabolism*
  • Peripheral Nerve Injuries / pathology
  • Synapses / metabolism*
  • Synapses / pathology
  • Synaptic Transmission / physiology*


  • CD56 Antigen
  • Ncam1 protein, mouse