The viruses used in this article from BrainVTA are in the table below

The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABAA receptor (GABAAR) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.

Fig.1 Using multiple tracing methods to dissect the dmPFC-vlPAG neural pathway.

In order to investigate the projection of dmPFC to vlPAG, the researchers used a variety of morphology and trans-synaptic virus tracing methods (From BrainVTA) to reveal two downward pain-regulating neural pathways. Finally, a dmPFC-vlPAG neural pathway was shown that it might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors. which provided a new target and scientific experimental basis for establishing an effective analgesic strategy.