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Anesth Analg 2001;93:1297-1303
© 2001 International Anesthesia Research Society

PAIN MEDICINE

The Interaction Between Intrathecal Neostigmine and GABA Receptor Agonists in Rats with Nerve Ligation Injury

Jai-Hyun Hwang, MD, Kyu-Sam Hwang, MD, Jong-Uk Kim, MD, In-Cheol Choi, MD, Pyung-Hwan Park, MD, and Sung-Min Han, MD

Department of Anesthesiology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea

Address correspondence and reprint requests to Jai-Hyun Hwang, MD, Department of Anesthesiology, Asan Medical Center, 388-1 Pungnap-Dong, Songpa-Ku, Seoul 138-736, Korea. Address e-mail to jhhwang{at}amc.seoul.kr

Nerve ligation injury may produce a pain syndrome that includes tactile allodynia. Reversal effects on tactile allodynia have been demonstrated after the intrathecal administration of {gamma}-aminobutyric acid (GABA) receptor agonists or cholinesterase inhibitors in rats. We examined the drug interactions between neostigmine and muscimol or baclofen in a rat model of nerve ligation injury. Rats were prepared with tight ligation of the left L5-6 spinal nerves and chronic intrathecal catheter implantation. Tactile allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hindpaw. Thresholds for paw withdrawal were assessed. Neostigmine (0.3–10 µg), muscimol (0.1–10 µg), and baclofen (0.1–3.0 µg) were administered to obtain the dose-response curve and the 50% effective dose (ED50). Fractions of ED50 values were administered intrathecally to establish the ED50s of drug combinations (neostigmine-muscimol and neostigmine-baclofen). The drug interactions were performed. Intrathecal neostigmine, muscimol, baclofen, and their combinations produced a dose-dependent increase in withdrawal threshold of the lesioned hindpaw. Both analyses revealed a synergistic interaction for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination was additive. These results suggest that the activation of both muscarinic and GABAA receptors is required for synergistic interaction.

IMPLICATIONS: This study indicates that drug interaction is synergistic for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination is additive. In a rat model of nerve ligation injury, neostigmine, muscimol, baclofen, and their combinations provide an antagonism on touch-evoked allodynia at the spinal level.






Lippincott, Williams & Wilkins 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 HighWire Press
Copyright © 2001 by the International Anesthesia Research Society.