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Updated: Jan 20, 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

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A G protein signaling-biased agonist at the μ-opioid receptor reverses morphine tolerance while preventing morphine

Travis W Grim1, Cullen L Schmid1, Edward L Stahl1

  • 1Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|August 24, 2019
PubMed

Insights

Biased opioid agonists like SR-17018 may offer pain relief without tolerance or dependence. This novel approach could treat opioid dependence while restoring pain sensitivity.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Drug Discovery

Background:

  • Opioid agonists acting on μ-opioid receptors can cause antinociception with fewer side effects.
  • Adverse effects of opioid therapeutics often emerge with prolonged use, necessitating safer alternatives.

Purpose of the Study:

  • To evaluate the onset of tolerance and dependence with chronic administration of the biased opioid agonist SR-17018.
  • To assess neurochemical adaptations associated with prolonged SR-17018 treatment.
  • To compare SR-17018's effects with morphine and buprenorphine in opioid-tolerant models.

Main Methods:

  • Chronic administration of SR-17018 to mice.
  • Assessment of antinociceptive tolerance using the hot plate test.
  • Evaluation of receptor desensitization and adenylyl cyclase activity in specific brain regions.
  • Substitution studies in morphine-tolerant mice.

Main Results:

  • SR-17018 did not induce antinociceptive tolerance, receptor desensitization, or adenylyl cyclase super-sensitization.
  • SR-17018 restored morphine potency and efficacy in tolerant mice.
  • SR-17018 prevented the onset of opioid withdrawal symptoms.
  • Unlike buprenorphine, SR-17018 did not maintain morphine antinociceptive tolerance.

Conclusions:

  • Biased opioid agonists like SR-17018 may provide a therapeutic strategy for managing opioid dependence.
  • These compounds show potential for treating opioid dependence while preserving or restoring opioid-mediated pain relief.

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