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Opioids Induce Bidirectional Synaptic Plasticity in a Brainstem Pain Center in the Rat
Valeria Mussetto1, Hannah Luise Teuchmann1, Bernhard Heinke1
1Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria.
The Journal of Pain
|May 7, 2023
Summary
Opioids cause long-term changes in brainstem pain pathways. Researchers discovered opioid-induced plasticity in the lateral parabrachial nucleus (LPBN), potentially explaining adverse effects like pain hypersensitivity.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Opioids are effective analgesics but cause neuroadaptations leading to side effects.
- The lateral parabrachial nucleus (LPBN) is crucial for pain and emotional processing.
- Opioid effects on LPBN synaptic plasticity were previously unknown.
Purpose of the Study:
- To investigate the impact of opioids on synaptic plasticity in the LPBN.
- To elucidate the mechanisms and pathways involved in opioid-induced plasticity in the LPBN.
Main Methods:
- Patch-clamp recordings in rat brainstem slices.
- Application of DAMGO (opioid agonist) at different concentrations.
- Optogenetic activation of spinal and periaqueductal gray matter (PAG) inputs to the LPBN.
Main Results:
- Low DAMGO concentration induced long-term depression (LTD) via metabotropic glutamate receptors.
- High DAMGO concentration induced long-term potentiation (LTP) requiring astrocytes and NMDARs.
- LTD occurred at all tested synapses, while LTP was specific to spino-parabrachial synapses.
Conclusions:
- Discovered novel forms of opioid-induced long-term plasticity in the LPBN.
- These findings may explain adverse opioid effects like hyperalgesia and aversion.
- Understanding LPBN plasticity could lead to new therapeutic strategies for opioid discontinuation.
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