Activation of extracellular signal-regulated protein kinase is associated with colorectal distension-induced spinal and supraspinal neuronal response and neonatal maternal separation-induced visceral hyperalgesia in rats

X. J. Zhang, Z. Li, E. K.Y. Chung, Hong Qi ZHANG, H. X. Xu, J. J.Y. Sung, Zhaoxiang BIAN*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

The activation of extracellular signal-regulated protein kinase (ERK) is essential for pain sensation and development of hyperalgesia in chronic pathological pain. Neonatal maternal separation (NMS) could trigger behavioral hyperalgesia and upregulate central neuronal activity in rats. The present study aims to investigate whether ERK associates with the colorectal distension (CRD)-evoked neuronal response and the upregulated central sensitivity to CRD in NMS rats. Male Sprague-Dawley rat pups were either subjected to NMS or not handled (NH) from postnatal day 2 to day 14. The protein expression of phospho-ERK (p-ERK) and c-fos at the spinal and supraspinal levels of adult rats were quantified and their correlation was analyzed. Western blot analysis revealed significant NMS effect on p-ERK expression in the lumbosacral dorsal horn and thalamus. Immunohistochemistry analysis demonstrated that CRD elevated p-ERK and c-fos expression in the dorsal root ganglia (DRG), laminae I-II of the lumbosacral dorsal horn, thalamic nucleus central medial (CM), paraventricular thalamic nucleus (PV), and anterior cingulate cortex (ACC). Significant NMS effect on p-ERK and c-fos expression was observed in the DRG, and laminae I-II, III-IV, and X of the lumbosacral dorsal horn. Furthermore, a significant interactive effect of NMS and CRD on p-ERK expression was observed in laminae III-IV of the lumbosacral dorsal horn. Correlation analysis revealed the positive association between c-fos- and p-ERK-immunoreactive nuclei numbers in the DRG, lumbosacral dorsal horn, and ACC. These results demonstrate that ERK is actively involved in CRD-evoked neuronal activation in both NH and NMS rats. Moreover, ERK is associated with the upregulated central neuronal sensitivity to noxious CRD in NMS rats, which may be responsible for the behavioral hyperalgesia in NMS rat.

Original languageEnglish
Pages (from-to)274-287
Number of pages14
JournalJournal of Molecular Neuroscience
Volume37
Issue number3
DOIs
Publication statusPublished - Mar 2009

Scopus Subject Areas

  • Cellular and Molecular Neuroscience

User-Defined Keywords

  • C-fos
  • ERK
  • Neonatal maternal separation
  • Visceral hyperalgesia

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