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Updated: Jun 14, 2025
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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
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Morphine-responsive neurons that regulate mechanical antinociception
Michael P Fatt1, Ming-Dong Zhang1, Jussi Kupari1
1Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 65 Stockholm, Sweden.
Science (New York, N.Y.)
|August 29, 2024
Summary
Researchers identified a specific brain circuit in mice that controls pain perception. This circuit, involving brain-derived neurotrophic factor (BDNF), explains how opioids like morphine reduce mechanical pain.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Opioids are effective analgesics but their precise mechanisms for pain relief are not fully understood.
- Opioid abuse has reached epidemic levels, necessitating a deeper understanding of their action.
- The neuroanatomical basis for opioid-mediated analgesia requires further elucidation.
Purpose of the Study:
- To identify the specific neural circuits in the brain responsible for opioid-induced pain relief.
- To investigate the role of rostral ventromedial medulla (RVM) neurons in mechanical nociception.
- To elucidate the molecular mechanisms underlying opioid analgesia.
Main Methods:
- Single-cell transcriptomics was employed to analyze gene expression in neurons.
- Manipulation of specific neuronal populations in the RVM was performed.
- Morphine-induced antinociception was assessed in a mouse model.
Main Results:
- An ensemble of neurons in the RVM was identified as critical for regulating mechanical nociception.
- Activation or silencing of RVMBDNF projection neurons directly impacted morphine's pain-relieving effects.
- A brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway and spinal galanin neurons were implicated.
Conclusions:
- A specific RVM-spinal circuit regulates mechanical pain perception.
- This circuit mediates the antinociceptive effects of morphine.
- Understanding this circuit offers potential for developing targeted pain management strategies.
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