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Persistent inflammation selectively activates opioid-sensitive phasic-firing neurons within the vlPAG
Kylie B McPherson1,2, Courtney A Bouchet1,2, Basile Coutens1
1Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, United States.
Journal of Neurophysiology
|April 19, 2023
Summary
Persistent inflammation activates specific opioid-sensitive neurons in the ventrolateral periaqueductal gray (vlPAG), offering new targets for pain therapies. This study identifies distinct vlPAG neuron types and their response to inflammation and opioids.
Area of Science:
- Neuroscience
- Pain research
- Cellular physiology
Background:
- The ventrolateral periaqueductal gray (vlPAG) is crucial for pain modulation and opioid analgesia.
- vlPAG neurons are diverse in their neurochemical and electrical properties.
- Understanding vlPAG neuron subtypes is key to developing targeted pain treatments.
Purpose of the Study:
- To classify vlPAG neurons based on intrinsic membrane properties.
- To determine if specific vlPAG neuron types are activated by inflammation.
- To investigate the role of mu-opioid receptors (MORs) in pain-responsive vlPAG neurons.
Main Methods:
- Electrophysiological recordings from 382 vlPAG neurons.
- Classification of neurons into four firing patterns: Phasic, Tonic, Onset, and Random.
- Assessment of MOR expression via GIRK currents activated by DAMGO.
- Induction of acute (2h) and persistent (5-7 days) inflammation using Complete Freund's Adjuvant (CFA).
Main Results:
- Four distinct vlPAG neuron types were identified: Phasic (48%), Tonic (33%), Onset (10%), and Random (9%).
- Opioid sensitivity, mediated by MORs, was present in all neuron types but did not correlate with firing patterns.
- Persistent inflammation selectively reduced the firing threshold of Phasic neurons, activating opioid-sensitive subtypes.
- Acute inflammation had no effect on vlPAG neuron firing patterns.
Conclusions:
- Intrinsic firing properties define distinct vlPAG neuron populations with varying opioid sensitivity.
- Persistent inflammation preferentially activates opioid-sensitive Phasic vlPAG neurons.
- This selective activation suggests a mechanism for vlPAG-mediated descending facilitation of pain, distinct from its known inhibitory role.
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