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Updated: Aug 18, 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

Spinal glucocorticoid receptors contribute to the development of morphine tolerance in rats

Grewo Lim1, Shuxing Wang, Qing Zeng

  • 1Pain Research Group, MGH Pain Center, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA 02114, USA.

Anesthesiology
|March 26, 2005
PubMed
Abstract

Insights

Spinal glucocorticoid receptors (GRs) significantly influence morphine tolerance. Blocking GRs with antagonists or antisense oligodeoxynucleotides attenuated tolerance, while agonists accelerated it, suggesting GRs are key in opioid therapy.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cellular Biology

Background:

  • Opioid analgesic tolerance is a complex cellular adaptation process.
  • Central glucocorticoid receptors (GRs) are implicated in neuronal plasticity, sharing mechanisms with opioid tolerance.
  • This study investigated the role of spinal GRs in morphine tolerance development.

Purpose of the Study:

  • To test the hypothesis that spinal GRs are crucial for developing tolerance to morphine's antinociceptive effects.
  • To explore the involvement of GRs in the cellular mechanisms underlying opioid tolerance.

Main Methods:

  • Rats received intrathecal morphine combined with GR antagonists (RU38486, spironolactone), GR antisense oligodeoxynucleotides, or GR agonists (dexamethasone).
  • Western blotting assessed GR expression in the spinal cord dorsal horn.
  • Morphine antinociceptive tolerance was evaluated using the tail-flick test.

Main Results:

  • Coadministration of GR antagonist RU38486 with morphine significantly attenuated tolerance development.
  • GR antisense oligodeoxynucleotides reduced morphine tolerance and prevented GR up-regulation.
  • GR agonist dexamethasone accelerated the development of morphine tolerance.

Conclusions:

  • Spinal GRs play a critical role in the cellular mechanisms of morphine tolerance in rats.
  • These findings suggest potential therapeutic strategies targeting GRs to manage clinical opioid therapy and mitigate tolerance.

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