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Updated: Jul 6, 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

Involvement of amlodipine, diazoxide, and glibenclamide in development of morphine tolerance in mice

Omid Khalilzadeh1, Mehdi Anvari, Azita Khalilzadeh

  • 1Department of Pharmacology and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.

The International Journal of Neuroscience
|March 7, 2008
PubMed

Insights

This study investigated how calcium and potassium channel modulators affect morphine tolerance. Amlodipine and diazoxide worsened morphine tolerance, while glibenclamide reduced it, suggesting channel involvement in opioid tolerance.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Management

Background:

  • Opioid tolerance, a common issue in pain management, necessitates understanding its underlying mechanisms.
  • Calcium and potassium channels are implicated in neuronal excitability and drug action.

Purpose of the Study:

  • To investigate the role of calcium and potassium channels in the development of morphine-induced tolerance.
  • To examine the effects of amlodipine, diazoxide, and glibenclamide on morphine tolerance in a preclinical pain model.

Main Methods:

  • The study utilized the formalin test to assess pain and tolerance.
  • Morphine was administered intraperitoneally (i.p.) in combination with varying doses of amlodipine, diazoxide, or glibenclamide.
  • Behavioral responses were measured in the first and second phases of the formalin test.

Main Results:

  • Co-administration of amlodipine (5-10 mg/kg) or diazoxide (1-10 mg/kg) with morphine potentiated morphine tolerance in both phases of the formalin test.
  • Glibenclamide (2.5-10 mg/kg) significantly decreased morphine tolerance in the second phase of the formalin test.

Conclusions:

  • Calcium channel blockade (amlodipine) and potassium channel opening (diazoxide) appear to enhance morphine tolerance.
  • Potassium channel blockade (glibenclamide) may attenuate morphine tolerance, particularly in later stages.
  • These findings suggest that calcium and potassium channel modulations are involved in the development of morphine tolerance.

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