Concurrent Assessment of the Antinociceptive and Behaviorally Disruptive Effects of Opioids in Squirrel Monkeys

The Journal of Pain : Official Journal of the American Pain Society
Sarah L WitheyJ Bergman

Abstract

Although the clinical application of opioids for pain management is often hindered by undesired behavioral impairment, preclinical assays of antinociception typically do not provide information regarding the behaviorally disruptive effects of opioids that may accompany their antinociceptive effects. To address this, we modified a warm water tail withdrawal procedure to determine concurrently the effects of opioids on tail withdrawal latency (antinociception) and indices of food-maintained operant behavior (rates of responding and reinforcement density) in squirrel monkeys. Six opioid agonists were tested, and all produced dose-dependent antinociception and impairment of operant behavior. The ratio of median effective dose (ED50) values for both measures (behavioral impairment:antinociception) was used as a quantitative measure of therapeutic index. Nalbuphine had the highest ED50 ratio (4.88), reflecting antinociception with minimal behavioral disruption. Oxycodone, heroin, buprenorphine, and methadone all produced similar ED50 ratios (.82-1.14), whereas butorphanol yielded a significantly lower ED50 ratio (.17) reflecting behavioral disruption at doses producing only minimal antinociception. The antinociceptive and behaviorall...Continue Reading

Citations

Apr 11, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Shawn M FlynnPaul W Czoty
Sep 14, 2018·Behavioural Pharmacology·Kathryn L SchwienteckMatthew L Banks
Sep 19, 2019·The Journal of Pharmacology and Experimental Therapeutics·Fernando Barreto de MouraJack Bergman
Jun 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Meining WangKenner C Rice
May 23, 2020·Perspectives on Behavior Science·Sarah L WitheyBrian D Kangas
Aug 16, 2019·The Journal of Pharmacology and Experimental Therapeutics·Sarah L WitheyCarol A Paronis
Jan 15, 2021·The Journal of Pharmacology and Experimental Therapeutics·Fernando B de Moura, Jack Bergman
Apr 9, 2021·Peptides·Richard J Bodnar

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