Time-Dependent Changes in Protein Composition of Medial Prefrontal Cortex in Rats with Neuropathic Pain

Hana Ujcikova, Dagoberto Robles, Xu Yue, Petr Svoboda, Yeon Sun Lee, Edita Navratilova

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic pain is associated with time-dependent structural and functional reorganization of the prefrontal cortex that may reflect adaptive pain compensatory and/or maladaptive pain-promoting mechanisms. However, the molecular underpinnings of these changes and whether there are time-dependent relationships to pain progression are not well characterized. In this study, we analyzed protein composition in the medial prefrontal cortex (mPFC) of rats at two timepoints after spinal nerve ligation (SNL) using two-dimensional gel electrophoresis (2D-ELFO) and liquid chromatog-raphy with tandem mass spectrometry (LC–MS/MS). SNL, but not sham-operated, rats developed persistent tactile allodynia and thermal hyperalgesia, confirming the presence of experimental neu-ropathic pain. Two weeks after SNL (early timepoint), we identified 11 proteins involved in signal transduction, protein transport, cell homeostasis, metabolism, and apoptosis, as well as heat-shock proteins and chaperones that were upregulated by more than 1.5-fold compared to the sham-operated rats. Interestingly, there were only four significantly altered proteins identified at 8 weeks after SNL (late timepoint). These findings demonstrate extensive time-dependent modifications of protein expression in the rat mPFC under a chronic neuropathic pain state that might underlie the evolution of chronic pain characterized by early pain-compensatory and later aberrant mechanisms.

Original languageEnglish (US)
Article number955
JournalInternational journal of molecular sciences
Volume23
Issue number2
DOIs
StatePublished - Jan 1 2022

Keywords

  • Affective dimension of pain
  • Neuropathic pain
  • Pain chronification
  • Prefrontal cortex
  • Proteomics

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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