From chronic pain to depression: Neurogenesis-driven microglial remodeling in the hippocampal dentate gyrus
Summary
Chronic pain often evolves into depression and anxiety, yet mechanisms linking sensory distress to affective dysfunction remain unclear. Integrating human neuroimaging from the UK Biobank with a rodent model, we uncovered biphasic hippocampal remodeling. Hippocampal volume increased during early pain stages, with paradoxical cognitive improvements, but declined with comorbid depression. In rodents, the dentate gyrus (DG) acted as a hub governing this transition: Lesions of DG prevented aff
Content
# From chronic pain to depression: Neurogenesis-driven microglial remodeling in the hippocampal dentate gyrus
*Published: 2026 Mar 19*
Chronic pain often evolves into depression and anxiety, yet mechanisms linking
sensory distress to affective dysfunction remain unclear. Integrating human
neuroimaging from the UK Biobank with a rodent model, we uncovered biphasic
hippocampal remodeling. Hippocampal volume increased during early pain stages,
with paradoxical cognitive improvements, but declined with comorbid depression.
In rodents, the dentate gyrus (DG) acted as a hub governing this transition:
Lesions of DG prevented affective symptoms. Elevated DG activity was linked to
hyperactive newborn neurons and microglial recruitment and remodeling, leading
to circuit imbalance. Whereas suppressing newborn neuron activity alleviated
emotional pathology at the expense of cognition, microglial modulation
selectively restored affective behavior without cognitive cost. These findings
reveal microglia-mediated hippocampal remodeling as a key mechanism linking
chronic pain to mood disorders.
DOI: 10.1126/science.aee6177