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Updated: Aug 10, 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

Oral administration of dextromethorphan prevents the development of morphine tolerance and dependence in rats

J Mao1, D D Price, F S Caruso

  • 1Department of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.

Pain
|October 1, 1996
PubMed

Insights

Combining morphine sulfate (MS) with dextromethorphan (DM) orally prevented tolerance and dependence on MS in rats. This combination also enhanced MS pain relief, suggesting a novel approach for managing pain and opioid-related side effects.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Management

Background:

  • Opioid analgesics like morphine sulfate (MS) are effective for pain but can lead to tolerance and dependence.
  • Dextromethorphan (DM), an NMDA receptor antagonist and antitussive, has shown potential in modulating opioid effects.

Purpose of the Study:

  • To investigate the efficacy of combined oral administration of MS and DM in preventing the development of tolerance and physical dependence on MS.
  • To assess whether DM can enhance the acute antinociceptive effects of MS.

Main Methods:

  • Rats were administered varying oral doses of MS alone or in combination with DM.
  • Tolerance to MS antinociception was assessed after repeated administration.
  • Physical dependence was evaluated through naloxone-precipitated withdrawal signs.
  • Acute antinociceptive effects of MS and DM combinations were measured.

Main Results:

  • Combined oral MS and DM administration prevented the development of tolerance to MS's antinociceptive effects across different MS doses.
  • This combination regimen also attenuated signs of naloxone-precipitated physical dependence on MS.
  • Various ratios of MS to DM (2:1, 1:1, 1:2) were effective in preventing tolerance and dependence.
  • DM was observed to enhance the acute antinociceptive effects of MS under certain conditions.

Conclusions:

  • Oral co-administration of dextromethorphan with morphine sulfate is a promising strategy for preventing opioid tolerance and dependence.
  • This combined approach may also enhance analgesia, offering a potential therapeutic advantage in pain management.
  • Further research into combining DM with opioid analgesics could lead to improved patient outcomes by mitigating major side effects.

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