N-Methyl-D-aspartate receptor antagonist MK-801 attenuates morphine tolerance and associated glial fibrillary acid protein up-regulation: a proteomic approach |
| |
Authors: | Wen Z-H Wu G-J Hsu L-C Chen W-F Chen J-Y Shui H-A Chou A-K Wong C-S |
| |
Institution: | Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan,;Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan,;College of Medicine, Fu Jen Catholic University, Taipei Hsien, Taiwan,;Core Facilities for Proteomics Research located at Academia Sinica, Taipei, Taiwan,;Department of Neurosurgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan,;National Defense Medical Center, Graduate Institute of Medical Sciences, Taipei, Taiwan,;Department of Anesthesiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan and;Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan |
| |
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. |
| |
Keywords: | morphine tolerance proteomics NMDA GFAP |
本文献已被 PubMed 等数据库收录! |
|