Understanding Paraventricular Thalamus (PVT) Mechanism for Pain & Anxiety Regulation
On May 8, 2025, Professor Guangyin Xu from Soochow University in Suzhou published a study in Neuron titled: "The paraventricular thalamus mediates visceral pain and anxiety-like behaviors via two distinct pathways." This research reveals that the paraventricular nucleus of the thalamus (PVT) mediates visceral pain and anxiety-like behaviors through two distinct pathways.
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Overview
Chronic visceral pain often goes hand-in-hand with emotional disorders. However, a lack of suitable animal models has limited research into the underlying molecular and neural circuit mechanisms. Early-life stress is a key factor in developing visceral hypersensitivity and emotional disorders, but its exact pathological mechanisms are still unclear.
This study found that adult mice exposed to prenatal maternal stress (PMS) developed both visceral hypersensitivity and anxiety-like behaviors. Specifically, glutamatergic neurons in the anterior paraventricular thalamus (aPVT) responded to visceral pain, while glutamatergic neurons in the posterior PVT (pPVT) were more sensitive to anxiety.
The research also identified distinct neural pathways:
- The pathway between the aPVT and the basolateral amygdala (BLA) modulated chronic visceral pain.
- The pathway between the pPVT and the central amygdala (CeA) primarily regulated anxiety-like behaviors.
At the molecular level, increased expression of the Cacna1e gene in the aPVT enhanced both visceral pain and anxiety responses. In the pPVT, however, upregulation of the Grin2a gene only promoted anxiety-like behaviors.
These findings highlight the distinct roles of the aPVTGlu-BLAGlu-CeAGABA and pPVTGlu-CeAGABA neural circuits in the comorbidity of chronic visceral pain and anxiety. This research offers new avenues for developing treatment strategies for these interconnected conditions.
Fig.1 PVT mediates visceral pain and anxiety via different molecular targets.1
Findings of the Study
This groundbreaking research has, for the first time, revealed that the Paraventricular Nucleus of the Thalamus (PVT) shows specialized functions in controlling visceral pain and anxiety. Specifically, the anterior PVT (aPVT) primarily regulates visceral pain, while the posterior PVT (pPVT) plays a crucial role in anxiety modulation.
Their downstream projection pathways also differ:
- For visceral pain, glutamatergic neurons in the aPVT (aPVT-Glu), activated by visceral pain, mainly project to glutamatergic neurons in the basolateral amygdala (BLA-Glu), forming the aPVT-Glu–BLA-Glu pathway that regulates visceral pain. Importantly, this pain pathway can also worsen anxiety by modulating GABAergic neurons in the central amygdala (CeA-GABA).
- For anxiety, conversely, glutamatergic neurons in the pPVT (pPVT-Glu), activated by anxiety, primarily project to GABAergic neurons in the central amygdala (CeA-GABA), forming the pPVT-Glu–CeA-GABA pathway. This pathway is involved in anxiety regulation but doesn't influence visceral pain.
This functional specialization within the PVT in managing chronic visceral pain and anxiety provides a strong theoretical basis for developing individualized treatments and targeted drug therapies in clinical settings.
Disclaimer: Please note that we do not provide the content above, nor do we hold copyright to it. This article is for informational and knowledge-sharing purposes only and does not constitute an offer of commercial services related to its subject matter.
Resources
Reference
- Li, Di et al. "The paraventricular thalamus mediates visceral pain and anxiety-like behaviors via two distinct pathways." Neuron, S0896-6273(25)00302-2. 6 May. 2025, doi:10.1016/j.neuron.2025.04.019. Distributed under Open Access license CC BY 4.0, without modification.
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