Reduced oxytocin signaling in the dBNST drives the transition from acute pain to persistent anxiety.

Transient sensory experiences can trigger sustained emotional disturbances, yet the underlying neural mechanisms remain unclear. Here, we show that acute pain induces persistent anxiety in male mice, independent of ongoing nociceptive input, through reduced oxytocin signaling in the dorsal bed nucleus of the stria terminalis (dBNST). Reactivating oxytocin receptors (Oxtrs) in the dBNST markedly alleviated anxiety-like behaviors following pain resolution. Mechanistically, chemogenetic inhibition of somatostatin-expressing (SST) neurons in the dBNST (dBNSTSST neurons) abolished oxytocin's anxiolytic effects, while pharmacological blockade or selective knockdown of Oxtrs in these neurons increased anxiety-like behaviors. Transcriptomic and electrophysiological analyses further revealed that alterations in synaptic transmission and intrinsic excitability participate in this anxiety state. Together, these findings define a multilevel framework-spanning molecular, cellular, and circuit mechanisms-by which acute sensory input induces long-term emotional dysregulation. This study advances our understanding of pain-related affective disorders and highlights oxytocin signaling and dBNSTSST neurons as promising therapeutic targets.