The effect of gamma-aminobutyric acid (GABA) receptor drugs on morphine-induced spastic paraparesis after a noninjurious interval of spinal cord ischemia in rats.

Abstract

UNLABELLED:

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 gamma-aminobutyric acid (GABA)ergic interneurons that control the tonus of spinal cord alpha-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.

• Authors: Seiya Nakamura, Manabu Kakinohana, Yutaka Taira, Hiroshi Iha, Kazuhiro Sugahara
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 95 Issue 5 Pg. 1389-95, table of contents (Nov 2002) ISSN: 0003-2999 [Print] United States
• PMID: 12401631 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• GABA Agonists
• GABA Antagonists
• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• GABA-B Receptor Agonists
• GABA-B Receptor Antagonists
• Receptors, GABA
• Morphine

Topics

• Analgesics, Opioid (administration & dosage, toxicity)
• Animals
• Dose-Response Relationship, Drug
• GABA Agonists (administration & dosage, pharmacology)
• GABA Antagonists (administration & dosage, pharmacology)
• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• GABA-B Receptor Agonists
• GABA-B Receptor Antagonists
• Injections, Spinal
• Male
• Morphine (administration & dosage, toxicity)
• Paraparesis (chemically induced, prevention & control)
• Rats
• Rats, Sprague-Dawley
• Receptors, GABA (drug effects)
• Reperfusion Injury (physiopathology)
• Spinal Cord Ischemia (complications)