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ANALGESIA

The Effect of Dexamethasone on Spinal Glutamine Synthetase and Glutamate Dehydrogenase Expression in Morphine-Tolerant Rats

Gong-Jhe Wu, MD^*, Zhi-Hong Wen, PhD, Wu-Fu Chen, MD, Yi-Chen Chang, MS^||, Chen-Hwan Cherng, MD, DMSc^||, and Chih-Shung Wong, MD, PhD^||

From the *Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, Fu-Jen Catholic University, Hsinchuang, Taipei County, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan; and ||Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.

Address correspondence and reprint requests to Chih-Shung Wong, MD, PhD, Department of Anesthesiology, Tri-Service General Hospital, 325 Chenggung Rd., Section 2, Neihu 114, Taipei, Taiwan. Address e-mail to w82556{at}ndmctsgh.edu.tw.

Abstract

BACKGROUND: Excitatory amino acids play an important role in morphine tolerance. Recently, we demonstrated that a single morphine challenge induces an increase in spinal cerebrospinal fluid excitatory amino acid concentrations in morphine-tolerant rats, and that dexamethasone inhibits the development of morphine tolerance. We further examined the effect of intrathecal dexamethasone infusion on the development of morphine tolerance and on expression of the intracellular glutamate metabolizing enzymes, glutamate dehydrogenase and glutamine synthetase, in the spinal cord.

METHODS: Male Wistar rats, implanted with an intrathecal catheter, were divided into four groups that were infused for 5 days with intrathecal morphine (15 µg/h), saline (1 µL/h), dexamethasone (2 µg/h), or dexamethasone (2 µg/h) plus morphine (15 µg/h). On Day 5, the spinal cords were removed and prepared for Western blot analysis of glutamate dehydrogenase and glutamate synthetase.

RESULTS: Glutamate dehydrogenase and glutamate synthetase concentrations were downregulated in the morphine-tolerant rat spinal cords. Concurrent infusion of dexamethasone attenuated morphine tolerance and the associated glutamate dehydrogenase and glutamate synthetase downregulation.

CONCLUSION: Intrathecal dexamethasone attenuates long-term morphine infusion-induced glutamate dehydrogenase and glutamate synthetase downregulation and antinociceptive tolerance.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999