EMBEDDEDIMAGEhttps://ama.dev.pubfactory.com/display/journals/ama-guides-newsl/26/5/article-p3-embeddedimages/F1.xmlFigure 1.; Changes in Opioid Analgesia and Pain During Tolerance and Hyperalgesia (A) Tolerance to opioid analgesia develops after ongoing exposure to the drug. The same dose of drug administered over time produces less analgesic effect. The rate of onset and extent of tolerance development is variable depending on the individual drug and patient characteristics. (B) Opioid analgesic tolerance produces a rightward shift in the dose-response relationship. (C) Opioid-induced hyperalgesia describes a paradoxical increase in pain sensitivity during ongoing exposure to opioid drugs. Although the timeline in the graph is not specified, and will vary between different opioids, in the case of remifentanil (0–1μg/kg per min),1 infusion for 30 min is sufficient to cause opioid-induced hyperalgesia.3 (D) Allodynia can occur after exposure to an opioid (ie, pain in response to stimuli that were of intensities [shaded red] below threshold before drug administration).2026-02-19