Downregulation of Cdh1 signalling in spinal dorsal horn contributes to the maintenance of mechanical allodynia after nerve injury in rats

Mol Pain. 2016 May 16;12:1744806916647376. doi: 10.1177/1744806916647376. Print 2016.

Abstract

Background: Anaphase-promoting complex/cyclosome (APC/C) and its co-activator Cdh1 are important ubiquitin-ligases in proliferating cells and terminally differentiated neurons. In recent years, APC/C-Cdh1 has been reported as an important complex contributing to synaptic development and transmission. Interestingly, cortical APC/C-Cdh1 is found to play a critical role in the maintenance of neuropathic pain, but it is not clear whether APC/C-Cdh1 in spinal dorsal cord is involved in molecular mechanisms of neuropathic pain conditions.

Results: Immunostaining showed that Cdh1 was mainly distributed in dorsal horn neurons of the spinal cord in rats. Its expression was downregulated in the ipsilateral dorsal horn at 14 days after spared nerve injury. Rescued expression of Cdh1 in spinal cord by intrathecal administration of recombinant lentivirus encoding Cdh1 (Lenti-Cdh1-GFP) significantly attenuated spared nerve injury-induced mechanical allodynia. Furthermore, rescued expression of spinal Cdh1 significantly reduced surface membrane expression of GluR1, but increased the expression of GluR1-related erythropoietin-producing human hepatocellular receptor A4 and its ligand EphrinA1 in dorsal horn of spared nerve injury-treated animals.

Conclusions: This study indicates that a downregulation of Cdh1 expression in spinal dorsal horn is involved in molecular mechanisms underlying the maintenance of neuropathic pain. Upregulation of spinal Cdh1 may be a promising approach to treat neuropathic pain.

Keywords: Anaphase-promoting complex; Cdh1; GluR1; neuropathic pain; spinal cord.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cdh1 Proteins / metabolism*
  • Cell Membrane / metabolism
  • Down-Regulation*
  • Green Fluorescent Proteins / metabolism
  • Hyperalgesia / metabolism*
  • Hyperalgesia / pathology
  • Injections, Spinal
  • Lentivirus / metabolism
  • Male
  • Posterior Horn Cells / metabolism
  • Posterior Horn Cells / pathology
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism
  • Signal Transduction*
  • Spinal Cord Dorsal Horn / metabolism*
  • Spinal Cord Dorsal Horn / pathology
  • Spinal Nerves / injuries*
  • Spinal Nerves / metabolism*

Substances

  • Cdh1 Proteins
  • Receptors, AMPA
  • Green Fluorescent Proteins
  • glutamate receptor ionotropic, AMPA 1