Morphine Antinociception Restored by Use of Methadone in the Morphine-Resistant Inflammatory Pain State

Chizuko Watanabe1, Asami Komiyama1, Masaru Yoshizumi1

  • 1Department of Physiology and Anatomy, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Japan.

Frontiers in Pharmacology
|December 21, 2020
PubMed

Insights

Methadone effectively treats inflammatory pain resistant to morphine. It restores morphine

Area of Science:

  • Pharmacology
  • Pain Management
  • Neuroscience

Background:

  • Inflammatory pain states can lead to reduced efficacy of common analgesics like morphine.
  • Understanding mechanisms of opioid resistance is crucial for developing effective pain therapies.

Purpose of the Study:

  • To investigate the antinociceptive effect of methadone in a morphine-resistant inflammatory pain model.
  • To determine if methadone can restore morphine's efficacy in this resistant state.

Main Methods:

  • Utilized the complete Freund's adjuvant (CFA)-induced mouse inflammatory pain model.
  • Assessed thermal hyperalgesia using the paw-withdrawal test.
  • Administered methadone, morphine, fentanyl, and oxycodone via subcutaneous (s.c.) injection.

Main Results:

  • Methadone maintained its antinociceptive effect in CFA-treated mice, unlike morphine, fentanyl, and oxycodone.
  • Methadone treatment restored suppressed morphine antinociception in the CFA model.
  • MK-801 also restored morphine antinociception, but pre-CFA morphine administration did not.

Conclusions:

  • Methadone is highly effective against thermal hyperalgesia in morphine-resistant inflammatory pain.
  • Methadone restores suppressed morphine antinociception without altering µ-opioid receptor mRNA expression.

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