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Updated: Jul 18, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

Morphine analgesic tolerance in 129P3/J and 129S6/SvEv mice

Camron D Bryant1, Kristofer W Roberts, Janet S Byun

  • 1Shirley and Stefan Hatos Center for Neuropharmacology, USA. cdbryant@ucla.edu

Pharmacology, Biochemistry, and Behavior
|January 2, 2007
PubMed

Insights

Morphine tolerance heritability depends on how it is measured. A between-subjects design revealed tolerance in mouse strains previously thought to be non-tolerant, impacting genetic studies.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Genetics

Background:

  • Morphine analgesic tolerance is a heritable trait in humans and rodents.
  • Certain mouse strains, like 129S6/SvEv and 129P3/J, have been reported to not develop morphine tolerance.
  • The methodology used to assess tolerance can influence observed outcomes.

Purpose of the Study:

  • To investigate the development of morphine tolerance in 129S6/SvEv and 129P3/J mice using a standard laboratory regimen.
  • To determine if the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 affects morphine tolerance development.
  • To compare tolerance development across different mouse strains and experimental designs.

Main Methods:

  • Utilized a between-subjects design with a standard morphine tolerance regimen.
  • Assessed analgesic efficacy using hot plate and tail withdrawal assays.
  • Administered MK-801 to evaluate its effect on morphine tolerance.

Main Results:

  • Tolerance to morphine analgesia was observed in 129S6/SvEv and CD-1 mice using a between-subjects design.
  • MK-801 blocked morphine tolerance in 129S6/SvEv and CD-1 mice.
  • Contrary to previous findings, 129P3/J mice developed tolerance when assessed with a between-subjects design and a single challenge dose, similar to C57BL/6J mice.
  • Spontaneous hyperalgesia and altered tail-flick response patterns were noted in tolerant C57BL/6J mice but not in 129P3/J mice.

Conclusions:

  • The method of assessing morphine tolerance significantly impacts the detection and characterization of this trait.
  • Tolerance development and associated phenomena like hyperalgesia vary between mouse strains depending on the assessment design.
  • These findings have implications for understanding the heritability of morphine tolerance and for gene mapping studies.

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