Opioid hyperalgesia and tolerance versus 5-HT1A receptor-mediated inverse tolerance

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.