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Updated: Aug 29, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Opioid hyperalgesia and tolerance versus 5-HT1A receptor-mediated inverse tolerance
Xiao-Jun Xu1, Francis Colpaert, Zsuzsanna Wiesenfeld-Hallin
1Department of Laboratory Medicine, Division of Clinical Neurophysiology, Karolinska Institutet, Huddinge University Hospital, S-141 86, Stockholm, Sweden.
Abstract:
In addition to analgesia, opioids also produce paradoxical hyperalgesic effects following acute and chronic treatment. In this article, we review the occurrence of this hyperalgesia under several conditions, and discuss the potential mechanisms and clinical implications. We also review recent evidence that paradoxical analgesia and inverse tolerance induced by stimulation of 5-HT(1A) receptors, which is a mirror image of opioid-induced hyperalgesia and tolerance, might achieve clinically significant analgesia in chronic pain.
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