Fig. 9: A model diagram illustrating the role of vmPFC nNOS-expressing neurons in chronic pain-induced anxiety.

During chronic pain, vmPFC nNOS-expressing neurons are stimulated by glutamatergic inputs from pPVT CaMKIIα+ pyramidal neurons. Activated nNOS-expressing neurons produce diffusing NO and cause the S-nitrosylation of AMPAR-interacting proteins in CaMKIIα+ pyramidal neurons, promoting AMPAR trafficking to the plasma membrane. Consequently, enhanced AMPAR function in vmPFC CaMKIIα+ pyramidal neurons leads to anxiety-related behaviors.