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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
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Analysis of the opioid-opioid combinations according to the nociceptive stimulus in mice

Asunción Romero1, Hugo F Miranda, Margarita M Puig

  • 1Department of Anaesthesiology, Physiopathology and Management of Pain, IMIM-Hospital del Mar, Universitat Autònoma de Barcelona, Dr. Aiguader, 88, 08003 Barcelona, Spain. mromero@imim.es

Pharmacological Research
|March 9, 2010
PubMed

Insights

Combining tramadol with fentanyl or morphine showed synergistic pain relief in mice, except in the hot plate test where interactions were additive. Opioid combinations depend on the stimulus and non-opioid pathways.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Management

Background:

  • Opioid analgesics like tramadol, fentanyl, and morphine are crucial for pain management.
  • Understanding drug interactions is vital for optimizing pain relief and minimizing side effects.

Purpose of the Study:

  • To characterize the antinociceptive effects of tramadol, fentanyl, and morphine, alone and in combination.
  • To investigate the type of interaction (synergistic, additive) between opioid combinations in different pain models.

Main Methods:

  • Utilized hot plate, acetic acid writhing, and formalin tests in mice to assess antinociception.
  • Employed interaction indexes and isobolographic analysis to quantify drug interactions.
  • Confirmed motor coordination using the standard rotarod test.

Main Results:

  • Fentanyl demonstrated the highest potency, followed by morphine and tramadol, with exceptions in specific pain test phases.
  • Synergistic antinociceptive interactions were observed when tramadol was combined with fentanyl or morphine in writhing and formalin tests.
  • Additive interactions were noted in the hot plate test, and fentanyl-morphine combinations showed additivity regardless of stimulus type.

Conclusions:

  • Opioid-opioid interactions are influenced by the nature of the nociceptive stimulus and non-opioid analgesic pathways.
  • The type of interaction between opioids can vary based on the specific drug combination and the pain model used.
  • These findings contribute to a better understanding of opioid pharmacodynamics and potential for combination therapies.

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