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Updated: Aug 9, 2026
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Increased running response to morphine in morphine-pretreated mice
Abstract:
The running response of B6AF1/J mice to 25 mg/kg of morphine sulfate was increased up to 3-fold when this dose was administered either twice daily for 5 days or once a week for 2 or 3 weeks. The effect of weekly pretreatment was proportional to the dose of morphine and lasted as long as 1 month after pretreatment was stopped. There was no sensitization when the mice were less than 15 days old at the time of pretreatment. Of the parental strains, untreated C57Bl/6J mice showed a good running response to morphine, while A/J mice showed little response. Pretreatment of either of these strains produced only slight sensitization. Pretreatment of the hybrids with levorphanol increased the response to morphine. Dextrorphan and naloxone were ineffective. Sensitization by morphine was blocked by naloxone. Increased morphine running was not associated with analgesic tolerance as measured by the tail-flick assay. Morphine pretreatment produced some increase in the running response to amphetamine and to cocaine. Pretreatment with amphetamine or cocaine did not increase the response to morphine.
Insights
Repeated morphine administration in mice significantly increased their running response, a phenomenon known as sensitization. This effect persisted for weeks and was blocked by naloxone, indicating opioid receptor involvement.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Opioid drugs like morphine are widely used for pain relief.
- Understanding the long-term effects of opioid administration, such as sensitization, is crucial for clinical practice.
- Previous research has explored opioid-induced behavioral changes, but the mechanisms of sensitization require further investigation.
Purpose of the Study:
- To investigate the development and characteristics of morphine-induced behavioral sensitization in B6AF1/J mice.
- To explore the role of opioid receptors and other drugs in modulating this sensitization.
- To determine if morphine-induced sensitization is associated with analgesic tolerance.
Main Methods:
- B6AF1/J mice and their parental strains (C57Bl/6J and A/J) were administered morphine sulfate or other drugs at various doses and frequencies.
- Locomotor activity (running response) was measured following drug administration.
- The tail-flick assay was used to assess analgesic tolerance.
- The effects of opioid antagonists and other psychostimulants were examined.
Main Results:
- Repeated morphine administration (twice daily for 5 days or weekly for 2-3 weeks) increased the running response in B6AF1/J mice up to threefold.
- This sensitization was dose-dependent, lasted up to a month after cessation of treatment, and was not observed in young mice (<15 days old).
- Morphine sensitization was blocked by naloxone but not by dextrorphan, and it did not lead to analgesic tolerance. Pretreatment with morphine also enhanced responses to amphetamine and cocaine.
Conclusions:
- Repeated morphine administration induces significant and long-lasting behavioral sensitization in mice, mediated by opioid receptors.
- This sensitization is distinct from analgesic tolerance and can cross-sensitize with other psychostimulants.
- The findings highlight the complex neuroadaptive changes associated with chronic opioid exposure.
