Overview

• A newly identified spinothalamic circuit in mice shows CGRP-expressing neurons in the parvocellular subparafascicular thalamus projecting directly to the amygdala to encode pain’s emotional component.
• Genetic silencing of these CGRP neurons preserved sensory pain responses while eliminating learned fear and avoidance behaviors in treated mice.
• Optogenetic activation of the CGRP pathway induced distress and conditioned avoidance in the absence of any physical pain stimulus.
• Single-cell transcriptomic profiling revealed that the CGRP thalamic neurons express multiple genes linked to migraine and other chronic pain conditions.
• Researchers intend to repurpose existing migraine drugs that block CGRP and advance studies to translate this pathway as a therapeutic target for human chronic and psychiatric pain.