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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective.
Emily O Dumas1, Gary M Pollack
1Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, The University of North Carolina at Chapel Hill, CB #7360, Kerr Hall 2311, Chapel Hill, NC 27599-7360, USA. emily.olson@abbott.com
The AAPS Journal
|November 8, 2008
Summary
Understanding opioid tolerance is key to developing better pain relief. This review explores how the body processes opioids and their effects, which can lead to reduced pain relief over time.
Area of Science:
- Pharmacology
- Neuroscience
- Pain Management
Background:
- Opioids are vital for managing acute and severe pain.
- Long-term opioid use faces a dose ceiling due to tolerance.
- Tolerance to side effects develops slower than analgesic tolerance, posing challenges.
Purpose of the Study:
- To explore the mechanisms underlying opioid tolerance.
- To identify factors contributing to the development of tolerance.
- To inform the development of novel analgesics and strategies for current opioid use.
Main Methods:
- Review of pharmacokinetic aspects of opioid tolerance (metabolism, enzymes, transporters).
- Review of pharmacodynamic aspects of opioid tolerance (receptors, signaling pathways, cross-tolerance).
- Examination of pharmacodynamic modeling strategies for characterizing tolerance.
Main Results:
- Opioid tolerance involves complex pharmacokinetic and pharmacodynamic changes.
- Understanding these changes is crucial for overcoming dose limitations.
- Pharmacodynamic modeling aids in characterizing the time-dependent loss of analgesia.
Conclusions:
- Further research into opioid tolerance mechanisms is essential for effective long-term pain management.
- Novel therapeutic strategies are needed to address tolerance.
- Pharmacodynamic modeling offers valuable insights into opioid efficacy over time.
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