N-Methyl-D-aspartate receptor antagonist MK-801 attenuates morphine tolerance and associated glial fibrillary acid protein up-regulation: A proteomic approach

Z. H. Wen, G. J. Wu, L. C. Hsu, W. F. Chen, J. Y. Chen, H. A. Shui, A. K. Chou, C. S. Wong

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: It is well known that long-term morphine administration results in tolerance, which limits the clinical use of this drug in pain management. Methods: Male Wistar rats were randomly assigned to receive one of four different infusions: morphine [15 μg/h, intrathecal (i.t.)], saline, MK-801 (5 μg/h, i.t.) plus morphine (15 μg/h, i.t.), or MK-801 (5 μg/h, i.t.) alone. Results: Morphine infusion induced a maximal antinociceptive effect on day 1 and tolerance on day 3, and the maximal anti-receptive tolerance was observed on day 5. Co-infusing MK-801 with morphine attenuated morphine's anti-receptive tolerance. Two-dimensional gel electrophoretic analysis of spinal proteins revealed that eight protein spots were up-regulated in morphine-tolerant rats, and that they were significantly inhibited by MK-801 co-infusion. Among the up-regulated proteins, glial fibrillary acid protein (GFAP), a glial-specific maker, was identified by mass spectrometry. This finding was also confirmed by Western blot analysis. Conclusion: Using proteomic analysis, we identified eight GFAP protein spots that were up-regulated in the dorsal horn of morphine-tolerant rat spinal cords. This up-regulation was partly inhibited by N-methyl-d-aspartate receptor antagonist MK-801 co-infusion, which suggests that GFAP protein can be considered to be a pathogenesis marker of morphine tolerance.

Original languageEnglish
Pages (from-to)499-508
Number of pages10
JournalActa Anaesthesiologica Scandinavica
Volume52
Issue number4
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

Keywords

  • GFAP
  • Morphine tolerance
  • NMDA
  • Proteomics

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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