A nociceptive amygdala-striatal pathway for chronic pain aversion

Area of Science:

• Neuroscience
• Pain Research
• Molecular Biology

Background:

• The basolateral amygdala (BLA) assigns emotional valence to stimuli.
• Noxious stimuli are encoded by nociceptive BLA projection neurons (BLA ensemble).
• The specific role and molecular characteristics of the BLA ensemble in pain remain unclear.

Purpose of the Study:

• Investigate the BLA ensemble's role in acute and chronic pain behaviors.
• Characterize the molecular signatures of the BLA ensemble under different pain states.
• Identify downstream targets of the BLA ensemble involved in pain processing.

Main Methods:

• Single nucleus RNA-sequencing of the BLA in acute and chronic pain models.
• Behavioral analysis of pain responses.
• Tracing of BLA ensemble neuronal projections.

Main Results:

• The same BLA ensemble neurons are essential for both acute and chronic neuropathic pain.
• Single nucleus RNA-sequencing revealed enrichment of genes related to axonal/synaptic organization and pain perception in the BLA.
• A previously unknown nociceptive nucleus accumbens shell (NAcSh) hotspot was identified as a downstream target, mirroring BLA ensemble activity and recruited in chronic pain.

Conclusions:

• The BLA nociceptive ensemble plays a vital role in mediating pain behaviors.
• A novel amygdala-striatal circuit, specifically the BLA-NAcSh pathway, transmits nociceptive information.
• This circuit is critical for affective-motivational responses across different pain states.