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

• Published in: CNS neuroscience & therapeutics Vol. 29; no. 11; pp. 3493 - 3506
• Main Authors: Li, Yu‐Jie, Du, Wei‐Jia, Liu, Rui, Zan, Gui‐Ying, Ye, Bing‐Lu, Li, Qian, Sheng, Zhi‐Hao, Yuan, Ya‐Wei, Song, Yu‐Jie, Liu, Jing‐Gen, Liu, Zhi‐Qiang
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.11.2023; John Wiley and Sons Inc
• Subjects: Amygdala; Animal behavior; Anxiety; Anxiety disorders; Brain; Emotions; Freund's adjuvant; Hormones; Inflammation; Laboratory animals; Life sciences; Microinjection; Neurons; Original; Oxytocin; Pain; Paraventricular nucleus; Photometry; Video recorders; China; anxiety; oxytocin; pain; central nucleus of the amygdala; paraventricular nucleus
• ISSN: 1755-5930; 1755-5949; 1755-5949
• DOI: 10.1111/cns.14282

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. 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. 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 -CeA circuit prevented anxiety-like behavior in response to inflammatory pain. The results of our study suggest that oxytocin has anti-anxiety effects and provide novel insights into the role of PVN -CeA projections in the regulation of anxiety-like behaviors induced by inflammatory pain.