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Updated: Jun 14, 2025

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

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Exploring the Role of Bergamot Polyphenols in Alleviating Morphine-Induced Hyperalgesia and Tolerance through

Sara Ilari1, Saverio Nucera2, Lucia Carmela Passacatini1

  • 1IRCCS San Raffaele Roma, 00166 Rome, Italy.

Nutrients
|August 29, 2024
PubMed

Insights

Repeated morphine use causes pain tolerance and oxidative stress by affecting mitochondrial proteins. Bergamot polyphenol fraction (BPF) and MnTBAP reversed these effects, offering potential therapeutic strategies.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Morphine is a key analgesic, but its long-term use leads to tolerance and oxidative stress.
  • Oxidative stress, driven by reactive oxygen species (ROS), impairs mitochondrial function.
  • Sirtuin 3 (SIRT3) is a mitochondrial protein crucial for regulating ROS via antioxidant enzymes like manganese superoxide dismutase (MnSOD).

Purpose of the Study:

  • To investigate SIRT3's role in morphine-induced hyperalgesia and tolerance.
  • To evaluate the antioxidant effects of bergamot polyphenol fraction (BPF) in mitigating morphine's side effects.

Main Methods:

  • Mice received repeated morphine doses, followed by acute morphine with or without BPF or MnTBAP.
  • Assessed spinal cord levels of malondialdehyde (MDA), nitration, and the activity of SIRT3, MnSOD, glutamine synthetase (GS), and glutamate 1 transporter (GLT1).

Main Results:

  • Repeated morphine administration induced antinociceptive tolerance and increased oxidative stress markers.
  • Morphine treatment led to decreased activity of mitochondrial SIRT3, MnSOD, GS, and GLT1.
  • Co-administration of BPF or MnTBAP with morphine prevented tolerance and normalized oxidative stress markers and enzyme activities.

Conclusions:

  • SIRT3 plays a critical role in the development of morphine tolerance and hyperalgesia.
  • BPF exhibits antioxidant properties that counteract morphine-induced oxidative stress and tolerance.
  • Targeting SIRT3 and oxidative stress pathways may offer new therapeutic avenues for managing pain and mitigating opioid side effects.
Keywords:
Sirtuin 3antioxidantshyperalgesiamitochondrial dysfunctionmorphine-induced toleranceoxidative stresspolyphenolstherapeutic approach

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