I am a
Home I AM A Search Login

Papers of the Week


Papers: 11 Mar 2023 - 17 Mar 2023

RESEARCH TYPE:
Basic Science, Psychology


Animal Studies, Molecular/Cellular, Neurobiology

PAIN TYPE:
Psychological/Comorbidities


2023 Mar 14


J Clin Invest


36917193

Elevated prelimbic cortex-to-basolateral amygdala circuit activity mediates comorbid anxiety-like behaviors in chronic pain.

Authors

Gao F, Huang J, Huang GB, You QL, Yao S, Zhao ST, Liu J, Wu CH, Chen GF, Liu SM, Yu Z, Zhou YL, Ning YP, Liu S, Hu BJ, Sun XD

Abstract

Chronic pain could cause both hyperalgesia and anxiety symptoms. How the two components are encoded in the brain remains unclear. The prelimbic cortex (PrL), a critical brain region for both nociceptive and emotional modulations, serves as an ideal medium for comparing the encoding of the two components. We report that PrL neurons projecting to the basolateral amygdala (PrLBLA) and those projecting to the ventrolateral periaqueductal gray (PrLl/vlPAG) were segregated and displayed elevated and reduced neuronal activity, respectively, during pain chronicity. Consistently, optogenetic suppression of PrL→BLA circuit reversed anxiety-like behaviors whereas activation of PrL→l/vlPAG circuit attenuated hyperalgesia in mice with chronic pain. Moreover, mechanistic studies indicated that elevated TNF-α/TNFR1 signaling in PrL caused increased insertion of GluA1 receptors into PrLBLA neurons contributing to anxiety-like behaviors in mice with chronic pain. Together, these results provide insights into the circuit and molecular mechanisms in PrL for controlling pain-related hyperalgesia and anxiety-like behaviors.