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Updated: Oct 13, 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

Morphine antinociception is enhanced in mdr1a gene-deficient mice

J Zong1, G M Pollack

  • 1Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill 27599-7360, USA.

Pharmaceutical Research
|August 24, 2000
PubMed
Abstract

Insights

P-glycoprotein (P-gp) reduces morphine

Area of Science:

  • Neuroscience
  • Pharmacology
  • Genetics

Background:

  • P-glycoprotein (P-gp) is a key efflux transporter in the central nervous system (CNS).
  • Previous research suggests P-gp influences opioid antinociception.

Purpose of the Study:

  • To investigate the role of P-gp in morphine antinociception.
  • To assess morphine's effects in mice lacking CNS P-gp expression (mdr1a gene knockout).

Main Methods:

  • Morphine administered to mdr1a(-/-) and wild-type mice.
  • Antinociception measured via tail-flick test.
  • Morphine concentrations analyzed in serum, brain, and spinal cord using HPLC.
  • Experiments included R(+)-verapamil, a P-gp inhibitor.

Main Results:

  • Morphine antinociception was significantly enhanced in mdr1a(-/-) mice (lower ED50).
  • Brain morphine concentrations were similar between groups.
  • R(+)-verapamil mimicked the effects seen in gene-deficient mice.
  • Spinal cord to serum morphine ratio was unaffected by P-gp deficiency.

Conclusions:

  • P-gp attenuates morphine's antinociceptive action.
  • This attenuation occurs by limiting morphine's distribution into the brain.
  • Findings support P-gp as a modulator of central opioid effects.

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