Role and Mechanism of Arcuate Nucleus POMC Neurons in Depression-Like Behavior of Chronic Pain.

Abstract

Patients with chronic pain often present with depression, and the specific neuronal populations and circuits underlying this phenomenon are yet to be fully characterized. Here, using a neuropathic pain model, we found that the development of chronic pain is accompanied by anxiety- and depressive-like behavior. Concurrently, we observed increased activity of Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus (ARC), and acute inhibition of this elevated ARCneuron activity could reverse the behavioral manifestations of depression. While activating POMC neurons in naïve mice did not induce significant behavioral changes, stimulating these neurons during the early phase of peripheral nerve injury promoted susceptibility to depression, thereby inducing depressive phenotypes. Further studies established a projection pathway from the ARC to the central amygdala (CeA), which controls the development of depressive-like behaviors in states of chronic neuropathic pain, rather than those due to chronic stress. These findings collectively indicate that chronic pain leads to persistent hyperactivity of POMC neurons. Our discoveries suggest that POMC neuronal dysfunction contributes to behavioral deficits associated with chronic pain.