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Updated: Jun 21, 2026
07:23
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Do opioids induce hyperalgesia in humans? An evidence-based structured review
David A Fishbain1, Brandly Cole, John E Lewis
1Department of Psychiatry, Miller School of Medicine at the University of Miami, Florida 33136, USA. d.fishbain@miami.edu
Pain Medicine (Malden, Mass.)
|July 15, 2009
Summary
Opioid-induced hyperalgesia (OIH) is common in rodents but evidence in humans is inconsistent. The strongest evidence for OIH in humans comes from studies involving opioid infusions in healthy volunteers, indicating a need for further clinical research.
Area of Science:
- Pharmacology
- Pain Medicine
- Clinical Research
Background:
- Opioid exposure decreases pain threshold in rodents, a phenomenon known as opioid-induced hyperalgesia (OIH).
- The consistency and evidence for OIH in humans remain unclear.
- This review systematically evaluates human studies on OIH across all evidence levels.
Purpose of the Study:
- To determine the consistency of evidence for opioid-induced hyperalgesia (OIH) in humans.
- To review all available human studies and case reports on OIH.
- To assess the validity of OIH hypotheses in human subjects.
Main Methods:
- Conducted comprehensive literature searches for OIH studies (human and animal).
- Included 48 human references addressing 10 OIH hypotheses after applying inclusion/exclusion criteria.
- Rated study quality using AHCPR guidelines and calculated consistency ratings for each hypothesis.
Main Results:
- Strongest evidence for OIH in humans was found in opioid infusion studies with normal volunteers measuring secondary hyperalgesia.
- Inconsistent evidence supported OIH in opioid infusions (volunteers/CPPs) and increased postoperative opioid needs.
- Insufficient evidence or uninterpretable results were found for other OIH hypotheses.
Conclusions:
- Sufficient evidence to support or refute OIH in humans is lacking, except for opioid infusions in healthy volunteers.
- Prospective clinical studies are needed to investigate OIH in chronic pain patients (CPPs).
- Future research should include pre- and post-opioid placement measurements and non-opioid control groups.
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