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Updated: Apr 25, 2026
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Assessment of morphine-induced hyperalgesia and analgesic tolerance in mice using thermal and mechanical nociceptive
Khadija Elhabazi1, Safia Ayachi1, Brigitte Ilien1
1Biotechnology and Cellular Signalling, UMR 7242 CNRS, Université de Strasbourg.
Abstract:
Opioid-induced hyperalgesia and tolerance severely impact the clinical efficacy of opiates as pain relievers in animals and humans. The molecular mechanisms underlying both phenomena are not well understood and their elucidation should benefit from the study of animal models and from the design of appropriate experimental protocols. We describe here a methodological approach for inducing, recording and quantifying morphine-induced hyperalgesia as well as for evidencing analgesic tolerance, using the tail-immersion and tail pressure tests in wild-type mice. As shown in the video, the protocol is divided into five sequential steps. Handling and habituation phases allow a safe determination of the basal nociceptive response of the animals. Chronic morphine administration induces significant hyperalgesia as shown by an increase in both thermal and mechanical sensitivity, whereas the comparison of analgesia time-courses after acute or repeated morphine treatment clearly indicates the development of tolerance manifested by a decline in analgesic response amplitude. This protocol may be similarly adapted to genetically modified mice in order to evaluate the role of individual genes in the modulation of nociception and morphine analgesia. It also provides a model system to investigate the effectiveness of potential therapeutic agents to improve opiate analgesic efficacy.
Insights
This study presents a new method to measure opioid-induced hyperalgesia and tolerance in mice. This protocol helps understand pain mechanisms and develop better pain relief strategies.
Area of Science:
- * Pharmacology
- * Neuroscience
- * Pain Research
Background:
- * Opioid-induced hyperalgesia and tolerance reduce the effectiveness of opioid pain relievers.
- * The underlying molecular mechanisms require further investigation.
- * Animal models are crucial for studying these phenomena.
Purpose of the Study:
- * To describe a methodological approach for inducing, recording, and quantifying morphine-induced hyperalgesia.
- * To demonstrate a method for evidencing analgesic tolerance to morphine.
- * To provide a model for investigating genetic factors and therapeutic agents related to nociception.
Main Methods:
- * Utilized tail-immersion and tail pressure tests in wild-type mice.
- * Employed a five-step protocol including handling, habituation, and chronic morphine administration.
- * Compared analgesia time-courses after acute versus repeated morphine treatment.
Main Results:
- * Chronic morphine administration significantly increased thermal and mechanical sensitivity, indicating hyperalgesia.
- * Repeated morphine treatment led to a decline in analgesic response amplitude, demonstrating tolerance.
- * The protocol allowed for basal nociceptive response determination.
Conclusions:
- * The described protocol effectively induces and quantifies opioid-induced hyperalgesia and tolerance in mice.
- * This methodology can be adapted for genetically modified mice to study gene function in nociception.
- * The model system aids in evaluating potential therapies to enhance opioid analgesic efficacy.
