Alderete J et al.
The Journal of Pain. 2025. https://doi.org/10.1016/j.jpain.2025.07.004
Summary:
This study investigates how mu opioid receptors (MORs) in dopamine D1, D2, and adenosine A2a receptor-expressing neurons influence pain perception and opioid analgesia. Using genetically modified mice, the authors selectively removed MORs from these neuron types and evaluated behavioral responses to pain and oxycodone.
The key findings show that:
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Deleting MORs from dopamine D1 receptor (D1R) neurons reduces opioid analgesia in a tonic inflammatory pain model (formalin test).
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Deleting MORs from dopamine D2 receptor (D2R) or A2a receptor neurons enhances opioid analgesia in the same model.
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These effects were specific to the formalin test and were not observed in acute thermal pain or nerve injury models.
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Hearteningly, MORs in these neurons do not appear to regulate baseline pain thresholds.
These results suggest that the endogenous opioid system modulates inflammatory—but not phasic—pain through dopamine-related pathways, and that distinct populations of medium spiny neurons in the striatum contribute in opposite ways to opioid pain relief.
Key takeaways:
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MORs in D1R neurons are required for full opioid effect in inflammatory pain.
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MORs in D2R and A2aR neurons may inhibit opioid analgesia.
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No impact on baseline thermal or neuropathic pain thresholds was observed.
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This may help explain varied clinical responses to opioids and inform pain treatment strategies.
Reference keywords for SEO: mu opioid receptor, dopamine receptor, D1R, D2R, A2aR, oxycodone, formalin test, analgesia, antinociception, tonic pain, opioid signaling, striatum, medium spiny neurons.
Thank you to The Journal of Pain for allowing the use of this article. We encourage readers to explore the journal and consider supporting organizations advancing research in pain and opioid pharmacology.