Paraventricular nucleus‐central amygdala oxytocinergic projection modulates pain‐related anxiety‐like behaviors in mice

AIMS: Anxiety disorders associated with pain are a common health problem. However, the underlying mechanisms remain poorly understood. We aimed to investigate the role of paraventricular nucleus (PVN)‐central nucleus of the amygdala (CeA) oxytocinergic projections in anxiety‐like behaviors induced by inflammatory pain. METHODS: After inflammatory pain induction by complete Freund's adjuvant (CFA), mice underwent elevated plus maze, light–dark transition test, and marble burying test to examine the anxiety‐like behaviors. Chemogenetic, optogenetic, and fiber photometry recordings were used to modulate and record the activity of the oxytocinergic projections of the PVN‐CeA. RESULTS: The key results are as follows: inflammatory pain‐induced anxiety‐like behaviors in mice accompanied by decreased activity of PVN oxytocin neurons. Chemogenetic activation of PVN oxytocin neurons prevented pain‐related anxiety‐like behaviors, whereas inhibition of PVN oxytocin neurons induced anxiety‐like behaviors in naïve mice. PVN oxytocin neurons projected directly to the CeA, and microinjection of oxytocin into the CeA blocked anxiety‐like behaviors. Inflammatory pain also decreased the activity of CeA neurons, and optogenetic activation of PVN(oxytocin)‐CeA circuit prevented anxiety‐like behavior in response to inflammatory pain. CONCLUSION: The results of our study suggest that oxytocin has anti‐anxiety effects and provide novel insights into the role of PVN(oxytocin)‐CeA projections in the regulation of anxiety‐like behaviors induced by inflammatory pain.