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Updated: Jun 3, 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

Potassium channel openers exhibit cross-tolerance with morphine in two experimental models of pain

N Khanna1, R S Malhotra, A K Mehta

  • 1Department of Pharmacology, University College of Medical Sciences University College of Medical Sciences (University of Delhi) Delhi 110095, India. naresh.khanna@gmail.com

The West Indian Medical Journal
|April 9, 2011
PubMed
Abstract

Insights

Morphine and potassium channel openers exhibit cross-tolerance, indicating their interaction occurs at the level of potassium channels, not receptors. This finding is crucial for understanding opioid tolerance mechanisms.

Area of Science:

  • Pharmacology
  • Neuroscience

Background:

  • Opioid tolerance, particularly to morphine, is a significant clinical challenge.
  • Potassium channels play a role in neuronal excitability and may influence opioid effects.

Purpose of the Study:

  • To investigate the reciprocal effects of potassium channel openers and morphine tolerance.
  • To determine if potassium channel openers influence the development of morphine tolerance.
  • To assess if morphine affects the action of potassium channel openers.

Main Methods:

  • Swiss albino mice were used to evaluate the effects of cromakalim, diazoxide, and minoxidil on morphine tolerance.
  • Formalin and tail-flick tests were employed to measure antinociceptive effects.
  • Animals were treated with potassium channel openers, morphine, or combinations thereof.

Main Results:

  • The antinociceptive effects of cromakalim and minoxidil were reduced in morphine-tolerant mice.
  • Diazoxide's analgesic effect was diminished in the formalin test but not the tail-flick test in tolerant mice.
  • Morphine administration to animals chronically treated with potassium channel openers led to tolerance.

Conclusions:

  • Morphine and potassium channel openers demonstrate cross-tolerance.
  • The interaction between morphine and potassium channel openers appears to occur at the level of potassium channels.
  • These findings suggest a shared pathway in the development of tolerance.

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