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NEUROSURGICAL ANESTHESIA

The Effect of Gamma-Aminobutyric Acid (GABA) Receptor Drugs on Morphine-Induced Spastic Paraparesis After a Noninjurious Interval of Spinal Cord Ischemia in Rats

Department of Anesthesiology, University of the Ryukyus, Okinawa, Japan

Address correspondence and reprint requests to Seiya Nakamura, MD, Department of Anesthesiology, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903–0215, Japan. Address e-mail to morph{at}ga2.so-net.ne.jp

We have previously demonstrated that intrathecal morphine given after a noninjurious interval of spinal cord ischemia induced transient spastic paraparesis in a rodent model. However, the mechanism of this paraparesis is unknown. We hypothesized that morphine inhibits -aminobutyric acid (GABA)ergic interneurons that control the tonus of spinal cord -motoneurons and that inhibition of spinal cord interneurons may cause spastic paraparesis. In this study, we investigate interactions between morphine and GABAergic agonists or antagonists on motor function after spinal cord ischemia and then clarified the mechanism of the spastic paraparesis induced by intrathecal morphine. Spinal cord ischemia was induced by aortic occlusion lasting 6 min. We first determined whether intrathecally administered GABA agonists (muscimol or baclofen) improve the spastic paraparesis in this model. GABA agonists did not improve the paraparesis. Next, we examined the effect of GABA antagonists (bicuculline or 5-aminovaleric acid) and determined the interaction between morphine and GABA antagonists. In an isobolographic analysis, the 50% effective dose decreased below the theoretical additive line, indicating a synergistic interaction between morphine and GABA antagonists. These results indicate that the spastic paraparesis induced by intrathecal morphine may be mediated in part by GABA receptors.

IMPLICATIONS: The purpose of this study was to investigate interactions between morphine and GABAergic agonists or antagonists on motor function after spinal cord ischemia and then clarify the mechanism of the spastic paraparesis induced by intrathecal morphine. The spastic paraparesis induced by intrathecal morphine may be mediated in part by GABA receptors.

This article has been cited by other articles:

				T. Fuchigami, M. Kakinohana, S. Nakamura, K. Murata, and K. Sugahara Intrathecal nicorandil and small-dose morphine can induce spastic paraparesis after a noninjurious interval of spinal cord ischemia in the rat. Anesth. Analg., April 1, 2006; 102(4): 1217 - 1222. [Abstract] [Full Text] [PDF]

				S. Nakamura, M. Kakinohana, K. Sugahara, S. Kinjo, and Y. Miyata Intrathecal Morphine, but Not Buprenorphine or Pentazocine, Can Induce Spastic Paraparesis After a Noninjurious Interval of Spinal Cord Ischemia in the Rat Anesth. Analg., November 1, 2004; 99(5): 1528 - 1531. [Abstract] [Full Text] [PDF]

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