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Updated: May 27, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

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Different effects of L-arginine on morphine tolerance in sham and ovariectomized female mice

Reza Karami1, Mahmoud Hosseini, Fatimeh Khodabandehloo

  • 1Neuroscience Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Iran.

Journal of Zhejiang University. Science. B
|December 3, 2011
PubMed
Abstract

Insights

L-arginine, a nitric oxide precursor, can prevent morphine tolerance in female mice. However, its effectiveness is influenced by the presence of ovarian hormones, indicating a complex interaction.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Endocrinology

Background:

  • Gonadal hormones and nitric oxide (NO) play roles in morphine analgesia and tolerance.
  • Understanding these interactions is crucial for optimizing pain management.

Purpose of the Study:

  • To investigate the effect of L-arginine, an NO precursor, on morphine tolerance in sham and ovariectomized (OVX) female mice.
  • To explore the influence of ovarian hormones on L-arginine's effect on morphine tolerance.

Main Methods:

  • Forty female mice were divided into sham and ovariectomized (OVX) groups.
  • Morphine tolerance was induced via repeated high-dose morphine administration.
  • L-arginine (50 mg/kg) or saline was administered to subgroups, followed by hot plate tests to assess the maximal percent effect (MPE) of morphine analgesia.

Main Results:

  • Repeated morphine administration significantly reduced its analgesic effect (MPE), indicating tolerance.
  • L-arginine administration partially prevented morphine tolerance in sham mice but not in OVX mice.
  • Ovariectomy itself did not alter morphine's analgesic effect, but the MPE in OVX-tolerant mice receiving saline was higher than in sham-tolerant mice receiving saline.

Conclusions:

  • Repeated morphine administration leads to tolerance to its analgesic effects.
  • L-arginine can prevent morphine tolerance, but this effect is modulated by ovarian hormones.
  • The findings highlight the interplay between NO, ovarian hormones, and morphine tolerance.

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