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Layer-specific pain relief pathways originating from primary motor cortex
Zheng Gan1, Vijayan Gangadharan1, Sheng Liu1
1Pharmacology Institute, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
Science (New York, N.Y.)
|December 22, 2022
Summary
The primary motor cortex (M1) uses distinct pathways to control neuropathic pain. One pathway reduces pain
Area of Science:
- Neuroscience
- Pain Research
- Motor Cortex Function
Background:
- The primary motor cortex (M1) is known for voluntary movement control.
- M1's role in pain modulation is established, but its specific neural circuits are unclear.
- Neuropathic pain involves both sensory and emotional components.
Purpose of the Study:
- To elucidate the distinct neural pathways originating from M1 that modulate neuropathic pain.
- To understand how M1 influences the sensory and emotional aspects of pain.
- To identify potential therapeutic targets within M1 circuitry for pain relief.
Main Methods:
- Utilized optogenetic and chemogenetic techniques in rodent models of neuropathic pain.
- Investigated neural projections from M1 to specific brain regions, including the nucleus accumbens, zona incerta, and periaqueductal gray.
- Assessed the impact of activating or inhibiting specific M1 neuronal populations on pain behaviors and sensory processing.
Main Results:
- Discovered a novel M1 pathway involving layer 6 neurons projecting to the mediodorsal thalamus and nucleus accumbens, which suppresses negative emotional valence in neuropathic pain.
- Identified a separate M1 pathway involving layer 5 neurons projecting to the zona incerta and periaqueductal gray, which reduces sensory hypersensitivity without affecting pain affect.
- Demonstrated that these layer-specific pathways differentially regulate the sensory and emotional components of neuropathic pain.
Conclusions:
- The primary motor cortex employs distinct, layer-specific circuits to independently control the sensory and emotional dimensions of neuropathic pain.
- Targeting M1 layer 6-mediodorsal thalamus-nucleus accumbens pathway may alleviate the affective suffering associated with pain.
- Targeting M1 layer 5-zona incerta-periaqueductal gray pathway may reduce pain hypersensitivity.
- These findings offer novel strategies for developing targeted pain relief interventions by modulating specific M1 circuits.
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