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Anesth Analg 2005;100:1733-1739
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000152192.23851.40

PAIN MEDICINE

Age-Dependent Morphine Tolerance Development in the Rat

Yan Wang, MD, James Mitchell, MD, Kumi Moriyama, MD, Ki-jun Kim, MD, PhD, Manohar Sharma, PhD, Guo-xi Xie, MD, PhD, and Pamela Pierce Palmer, MD, PhD

Department of Anesthesia and Perioperative Care, University of California, San Francisco

Address correspondence and reprint requests to Pamela Pierce Palmer, MD, PhD, Department of Anesthesia and Perioperative Care, University of California, San Francisco, 513 Parnassus Ave., Box 0464, Room S-455, San Francisco, CA 94143. Address e-mail to palmerp{at}anesthesia.ucsf.edu.

In all age groups, the use of opioids to treat chronic pain conditions has increased, yet the impact of age on opioid tolerance development has not been comprehensively addressed. In this study, we investigated age-related differences in morphine tolerance development in rats. Rats aged 3 wk, 3 mo, 6 mo, and 1 yr were used in the study. Morphine (8 mg/kg) was injected subcutaneously twice each day and its analgesic effect assessed by the change in tail-flick latency using a thermal stimulus 5 min before and 30 min after dosing. Tolerance was defined as a 75% reduction in morphine-induced analgesia compared to Day 1. Rats aged 3 wk, 3 mo, 6 mo, and 1 yr developed tolerance on the 4th, 10th, 14th, and 22nd days of morphine treatment, respectively. Plasma levels of morphine and its metabolites showed that pharmacokinetic differences among the groups did not correlate with the differences in tolerance development. This study demonstrates that morphine tolerance occurs more rapidly in younger rats than older rats and is unlikely to be the result of differences in drug metabolism or clearance. Aging may impact molecular processes involved in tolerance development and provide insight into novel therapeutic targets to delay opioid tolerance development.




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C. W. Agin and P. S. A. Glass
Tolerance and Aging: Optimizing Analgesia in Pain Management
Anesth. Analg., June 1, 2005; 100(6): 1731 - 1732.
[Full Text] [PDF]

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C. Buntin-Mushock, L. Phillip, K. Moriyama, and P. P. Palmer
Age-Dependent Opioid Escalation in Chronic Pain Patients
Anesth. Analg., June 1, 2005; 100(6): 1740 - 1745.
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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 © 2005 by the International Anesthesia Research Society.