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Papers of the Week

Papers: 16 May 2020 - 22 May 2020


Animal Studies

2020 May 19

Nat Commun



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nNOS-expressing neurons in the vmPFC transform pPVT-derived chronic pain signals into anxiety behaviors.


Liang H-Y, Chen Z-J, Xiao H, Lin Y-H, Hu Y-Y, Chang L, Wu H-Y, Wang P, Lu W, Zhu D-Y, Luo C-X
Nat Commun. 2020 May 19; 11(1):2501.
PMID: 32427844.


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.