NNOS-expressing Neurons in the VmPFC Transform PPVT-derived Chronic Pain Signals into Anxiety Behaviors

Overview

Journal Nat Commun

Specialty Biology

Date 2020 May 20

PMID 32427844

Citations 34

Authors

Hai-Ying Liang

Zhi-Jin Chen

Hui Xiao

Yu-Hui Lin

Ying-Yi Hu

Lei Chang

Hai-Yin Wu

Peng Wang

Wei Lu

Dong-Ya Zhu

Chun-Xia Luo

Affiliations

Soon will be listed here.

Abstract

Anxiety is common in patients suffering from chronic pain. Here, we report anxiety-like behaviors in mouse models of chronic pain and reveal that nNOS-expressing neurons in ventromedial prefrontal cortex (vmPFC) are essential for pain-induced anxiety but not algesia, using optogenetic and chemogenetic strategies. Additionally, we determined that excitatory projections from the posterior subregion of paraventricular thalamic nucleus (pPVT) provide a neuronal input that drives the activation of vmPFC nNOS-expressing neurons in our chronic pain models. Our results suggest that the pain signal becomes an anxiety signal after activation of vmPFC nNOS-expressing neurons, which causes subsequent release of nitric oxide (NO). Finally, we show that the downstream molecular mechanisms of NO likely involve enhanced glutamate transmission in vmPFC CaMKIIα-expressing neurons through S-nitrosylation-induced AMPAR trafficking. Overall, our data suggest that pPVT excitatory neurons drive chronic pain-induced anxiety through activation of vmPFC nNOS-expressing neurons, resulting in NO-mediated AMPAR trafficking in vmPFC pyramidal neurons.

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