Stepwise engagement of cingulate ensembles underlies motivational decline in chronic pain.

Stage-dependent engagement of anterior cingulate cortex circuits underpins sensory hypersensitivity and motivational decline in chronic pain, with distinct projections to BLA and LHb involved.

• Why it matters: Understanding how specific brain circuits contribute to different stages of chronic pain can inform targeted interventions for sensory and motivational symptoms.
• What they did: Using whole-brain activity-dependent tagging, projection-specific perturbations, in vivo Ca2+ imaging, and single-unit recordings in male mice, the study identified ACC circuits engaged at different pain stages, focusing on projections to BLA and LHb.
• The result: Findings suggest early ACC→BLA neurons are linked to hypersensitivity, while later ACC→LHb neurons relate to effortful persistence impairment, revealing a temporally organized circuit framework for pain-related behaviors.