Paraventricular nucleus-central amygdala oxytocinergic projection
modulates pain-induced anxiety-like behaviours in mice
Abstract
Background and Purpose: 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 behaviours induced by inflammatory pain. Experimental
Approach: Complete Freund’s adjuvant (CFA)-induced inflammatory pain
model was used to induce the anxiety-like behaviours. Chemogenetic,
optogenetic and fibre photometry recordings were used to modulate and
record the activity of the oxytocinergic projections of the PVN-CeA. Key
Results: Inflammatory pain induced anxiety-like behaviours in mice
accompanied by decreased activity of PVN oxytocin neurons. Chemogenetic
activation of PVN oxytocin neurons prevented pain-related anxiety-like
behaviours, whereas inhibition of PVN oxytocin neurons induced
anxiety-like behaviours in naive mice. PVN oxytocin neurons projected
directly to the CeA, and microinjection of oxytocin into the CeA blocked
anxiety-like behaviours. Inflammatory pain also decreased the activity
of CeA neurons, and optogenetic activation of PVNoxytocin -CeA circuits
prevented anxiety-like behaviour in response to inflammatory pain.
Conclusion and Implications: Our study suggests that oxytocin has
anti-anxiety effects and provides novel insights into the role of
PVN-CeA oxytocin projections in the regulation of anxiety-like
behaviours induced by inflammatory pain.