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Updated: May 15, 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

The combination of mitragynine and morphine prevents the development of morphine tolerance in mice

Sharida Fakurazi1, Shamima Abdul Rahman, Mohamad Taufik Hidayat

  • 1Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. sharida@medic.upm.edu.my

Molecules (Basel, Switzerland)
|January 8, 2013
PubMed

Insights

Mitragynine combined with morphine enhances pain relief and reduces tolerance to morphine in mice. This combination therapy shows potential for improved pain management strategies.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Natural Products Chemistry

Background:

  • Mitragynine (MG), the primary alkaloid in Mitragyna speciosa, is known for its analgesic properties.
  • Morphine is a potent opioid analgesic, but its chronic use leads to tolerance.
  • Investigating synergistic or additive effects of natural compounds with opioids is crucial for developing safer analgesics.

Purpose of the Study:

  • To evaluate the analgesic efficacy of combining mitragynine with morphine.
  • To determine the impact of this combination on the development of morphine tolerance.
  • To assess the effects on key molecular pathways and toxicological parameters.

Main Methods:

  • Mice were treated with varying doses of mitragynine and morphine for nine days.
  • Antinociceptive effects were measured using the hot plate test.
  • Protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed via immunoblotting.
  • Liver and kidney function tests were conducted to assess toxicity.

Main Results:

  • The combination of mitragynine and morphine significantly increased pain latency compared to morphine alone, maintaining efficacy over nine days.
  • While morphine alone increased cAMP and CREB levels, the combination treatment did not significantly alter these protein expressions.
  • Significant changes in toxicological parameters were observed across different treatment groups.
  • Chronic administration of morphine led to tolerance, which was effectively reduced by the combination treatment.

Conclusions:

  • Combining mitragynine with morphine offers enhanced analgesic effects and mitigates the development of morphine tolerance.
  • The molecular mechanisms underlying this effect warrant further investigation.
  • This combination therapy presents a promising strategy for managing pain and reducing opioid-induced tolerance.

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