A neural circuit for the suppression of feeding under persistent pain

In humans, persistent pain often leads to decreased appetite. However, the neural circuits underlying this behaviour remain unclear. Here, we show that a circuit arising from glutamatergic neurons in the anterior cingulate cortex (Glu^ACC) projects to glutamatergic neurons in the lateral hypothalamic area (Glu^LHA) to blunt food intake in a mouse model of persistent pain. In turn, these Glu^LHA neurons project to pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus (POMC^Arc), a well-known neuronal population involved in decreasing food intake. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that the Glu^ACC → Glu^LHA → Arc circuit is activated in mouse models of persistent pain and is accompanied by decreased feeding behaviour in both males and females. Inhibition of this circuit using chemogenetics can alleviate the feeding suppression symptoms. Our study indicates that the Glu^ACC → Glu^LHA → Arc circuit is involved in driving the suppression of feeding under persistent pain through POMC neuronal activity. This previously unrecognized pathway could be explored as a potential target for pain-associated diseases.