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A Comparison of the Antinociceptive and Behavioral Effects of Intrathecally Administered Opiates, -2-Adrenergic Agonists, and Local Anesthetics in Mice and Rats

Received from Anaquest, BOC Health Care, 100 Mountain Avenue, Murray Hill, New Jersey.

Abstract

This study was undertaken to compare the antinociceptive and behavioral effects of intrathecally administered opiates, -2-adrenergic agonists, and local anesthetics injected by lumbar puncture in the mouse and rat. Antinociception was determined by observing the response to a clamp applied to the tail (Haffner test) of the mouse and by the rat tail-flick test; log dose-response curves for antinociception were generated for each drug in each test. Motor coordination and other behavioral effects were also observed. Morphine and fentanyl (µ-opiate agonists) as well as ethylketocycla-zocine (EKC) and U50488H (K-opiate agonists), together with buprenorphine (partial µ-opiate agonist) and the -2-adrenergic agonist clonidine, all produced antinociception in both species without causing significant behavioral or motor dysfunctions at antinociceptive doses. Xylazine (also an -2-adrenergic agonist), ketamine, procaine, and lidocaine inhibited responses but only at doses that also produced motor impairment or paralysis. Nalbuphine (mixed opiate agonist-antagonist) was without any effect in both species. These data suggest that the µ-and K-opiate agonists and clonidine are the preferred agents for producing antinociception without compromising motor function.

Key Words: ANALGESICS, INTRATHECAL—morphine, fentanyl • ANESTHETIC TECHNIQUES—spinal • SYMPATHETIC NERVOUS SYSTEM, PHARMACOLOGY—clonidine

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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