The left PBN to aCM pathway mediates pain-related aversion in male mice.

Pain involves both sensory and emotional components, while the circuit mechanisms underlying pain-induced aversion remain poorly understood. Here, using a formalin-induced conditioned place aversion (F-CPA) model, we show a pathway from the left parabrachial nucleus (L-PBN) to the anterior central medial thalamic nucleus (aCM) that modulates F-CPA in male mice. We find that L-PBN neurons exhibit higher F-CPA-induced activity than those in the right PBN (R-PBN). Chemogenetic inhibition of L-PBN-but not R-PBN-attenuates F-CPA, whereas optogenetic activation of F-CPA-tagged L-PBN neurons induces aversion. Furthermore, the aCM-but not posterior CM-is activated by F-CPA, and inhibition of either the L-PBN to aCM pathway or aCM neurons receiving L-PBN inputs significantly reduces F-CPA. In contrast, in female mice, inhibition of neither L-PBN nor R-PBN affects F-CPA. Collectively, these findings identifies a neural circuit underlying pain-related aversion in male mice, advancing our understanding of sexual dimorphism in pain-related affective processing.