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Updated: Aug 7, 2026
02:26
Intracranial Pharmacotherapy and Pain Assays in Rodents
Published on: April 9, 2019
Drug-opposite neuroadaptation and breakthrough pain
Jane C Ballantyne1, George F Koob2
1Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA, United States.
The Journal of Pain
|August 4, 2026
Summary
Breakthrough pain may be caused by opioid tolerance, not inadequate dosing. This neuroadaptation can lead to increased pain and dependence, suggesting a need for different treatment strategies.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Management
Background:
- Extended-release/long-acting opioids introduced the concept of breakthrough pain.
- Breakthrough pain is often attributed to inadequate opioid dosing.
- An alternative explanation involves drug opposite neuroadaptation or tolerance.
Purpose of the Study:
- To describe the neurobiological basis of opioid tolerance.
- To highlight the futility of increasing opioid doses to overcome tolerance.
- To propose that breakthrough pain may be withdrawal hyperalgesia.
Main Methods:
- Literature review on opioid neurobiology and pain mechanisms.
- Analysis of the concept of negative reinforcement in opioid use.
- Exploration of neuroadaptation as an alternative explanation for opioid efficacy changes.
Main Results:
- Opioid tolerance can lead to rebound pain, mimicking breakthrough pain.
- Increasing opioid doses can exacerbate tolerance and dependence.
- Withdrawal hyperalgesia may be a more accurate description of opioid-induced pain.
Conclusions:
- Neuroadaptation offers a potential explanation for breakthrough pain.
- Rethinking breakthrough pain management is crucial for optimizing opioid efficacy.
- Alternative strategies are needed to reduce the risk of opioid dependence.
Keywords:
Breakthrough painDependenceHyperalgesiaHyperkatifeiaOpioid use disorderOpioidsPainProtracted withdrawalToleranceWithdrawalMore Related Videos
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