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Anesth Analg 1999;89:422
© 1999 International Anesthesia Research Society

REGIONAL ANESTHESIA AND PAIN MANAGEMENT

The Interaction of Antinociceptive Effects of Morphine and GABA Receptor Agonists Within the Rat Spinal Cord

Kaoru Hara, MD, Yoji Saito, MD, Yumiko Kirihara, DVM, Yuko Yamada, MD, Shinichi Sakura, MD, and Yoshihiro Kosaka, MD

Department of Anesthesiology, Shimane Medical University, Izumo, Shimane, Japan

Address correspondence to Y. Saito, MD, Department of Anesthesiology, Shimane Medical University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. Address e-mail to ysaito{at}shimane-med.ac.jp

Previous reports indicate that there may be an interaction between {gamma}-aminobutyric acid receptors and opioid receptors systems within the spinal cord, the antinociceptive effects of which have not been elucidated. We examined the effects of intrathecally coadministered morphine and muscimol or baclofen on somatic and visceral antinociception in rats. The tail flick (TF) test and colorectal distension (CD) test were used to assess somatic and visceral antinociceptive effects, respectively. Motor function was also assessed. The measurements were performed for 180 min after the intrathecal administration of morphine (0.1–10 µg), muscimol (0.2–10 µg), baclofen (0.03–1 µg), combination of morphine and muscimol or baclofen, or saline. Morphine, muscimol, or baclofen increased both TF latency and CD threshold in a dose-dependent fashion. Although morphine 0.1 µg, muscimol 0.2 µg, or baclofen 0.03 µg alone did not significantly increase TF latency and CD threshold, the combination of morphine 0.1 µg and muscimol 0.2 µg or baclofen 0.03 µg significantly increased both TF latency and CD threshold. The coadministration of muscimol or baclofen increased the antinociceptive effects of morphine in intensity and duration. None of the rats showed motor dysfunction after the coadministration of morphine and muscimol 0.2 µg, although muscimol produced motor paralysis of the lower limbs in a dose-dependent fashion. Those results suggest a clinical relevance of the coadministration of µ-opioids and GABA receptor agonists for pain control.

Implications: We examined the antinociceptive interaction between morphine and muscimol or baclofen at the spinal level in rats. Intrathecal muscimol or baclofen potentiated both somatic and visceral antinociceptive effects of morphine.




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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 © 1999 by the International Anesthesia Research Society.