Neuroscience

Prefrontal cortex

Biology

Cognition

Ventral tegmental area

Photostimulation

Dopamine

Conditioned place preference

Dopaminergic

Neuropathic pain

Psychology

Central nervous system

Midbrain

Periaqueductal gray

Optogenetics

Medicine

Neuroplasticity

Cell Reports

The medial prefrontal cortex (mPFC) is a brain region involved in the affective components of pain and undergoes plasticity during the development of chronic pain. Dopamine (DA) is a key neuromodulator in the mesocortical circuit and modulates working memory and aversion. Although DA inputs into the mPFC are known to modulate plasticity, whether and how these inputs affect pain remains incompletely understood. By using optogenetics, we find that phasic activation of DA inputs from the ventral tegmental area (VTA) into the mPFC reduce mechanical hypersensitivity during neuropathic pain states. Mice with neuropathic pain exhibit a preference for contexts paired with photostimulation of DA terminals in the mPFC. Fiber photometry-based calcium imaging reveals that DA increases the activity of mPFC neurons projecting to the ventrolateral periaqueductal gray (vlPAG). Together, our findings indicate an important role of mPFC DA signaling in pain modulation.

Dopamine Inputs from the Ventral Tegmental Area into the Medial Prefrontal Cortex Modulate Neuropathic Pain-Associated Behaviors in Mice