Paraventricular Nucleus-central Amygdala Oxytocinergic Projection Modulates Pain-related Anxiety-like Behaviors in Mice
Overview
Authors
Affiliations
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 -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 -CeA projections in the regulation of anxiety-like behaviors induced by inflammatory pain.
Dorsal raphe GABA-ergic neurons regulate the susceptibility to social transfer of pain in mice.
Ai L, Han Y, Ge T, Sha S, Zhai X, Ji R Acta Pharmacol Sin. 2025; .
PMID: 40011629 DOI: 10.1038/s41401-025-01494-x.
Lu J, Dou J, Yi Z, Lian L, Ben X, Zhang F Mol Pain. 2025; 21:17448069251324645.
PMID: 39962353 PMC: 11894642. DOI: 10.1177/17448069251324645.
Chronic Pain and Comorbid Emotional Disorders: Neural Circuitry and Neuroimmunity Pathways.
Li M, She K, Zhu P, Li Z, Liu J, Luo F Int J Mol Sci. 2025; 26(2).
PMID: 39859152 PMC: 11764837. DOI: 10.3390/ijms26020436.
Bahi A, Dreyer J Biomolecules. 2025; 14(12.
PMID: 39766310 PMC: 11674468. DOI: 10.3390/biom14121603.
Analgesic effect of oxytocin in alcohol-dependent male and female rats.
Marendes J, Muench M, Young C, Ghaly A, Tunstall B Alcohol. 2024; 123:27-38.
PMID: 39716604 PMC: 11875206. DOI: 10.1016/j.alcohol.2024.12.002.