The paraventricular thalamus mediates visceral pain and anxiety-like behaviors via two distinct pathways

Abstract

Chronic visceral pain (CVP) often accompanies emotional disorders. However, the lack of suitable animal models has hindered research into their underlying molecular and neural circuitry mechanisms. Early-life stress is a key factor in developing both visceral hypersensitivity and emotional disorders, yet its pathological mechanisms are not well understood. This study showed that adult offspring of prenatal maternal stress (PMS)-exposed mice exhibited visceral hypersensitivity and anxiety-like behaviors. Glutamatergic neurons in the anterior paraventricular thalamus (aPVT) responded to visceral pain, while those in the posterior PVT (pPVT) were more responsive to anxiety. The aPVT-basolateral amygdala (BLA) and pPVT-central amygdala (CeA) circuits regulated CVP and anxiety, respectively. Notably, increased Cacna1e expression in aPVT enhanced both visceral pain and anxiety, while Grin2a upregulation in pPVT facilitated only anxiety. These findings highlight the distinct roles of aPVT^Glu-BLA^Glu-CeA^GABA and pPVT^Glu-CeA^GABA circuits, providing insights for therapeutic approaches in CVP and anxiety comorbidity.

Keywords: anxiety; basolateral amygdala; central amygdaloid nucleus; chronic visceral pain; neural circuits; paraventricular thalamus nucleus.