Elevated prelimbic cortex-to-basolateral amygdala circuit activity mediates comorbid anxiety-like behaviors associated with chronic pain. 2023

Feng Gao, and Jie Huang, and Guo-Bin Huang, and Qiang-Long You, and Shan Yao, and Shen-Ting Zhao, and Jian Liu, and Cui-Hong Wu, and Gui-Fu Chen, and Shi-Min Liu, and Zongyan Yu, and Yan-Ling Zhou, and Yu-Ping Ning, and Shenquan Liu, and Bing-Jie Hu, and Xiang-Dong Sun
Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, and Emergency Department of the Second Affiliated Hospital, School of Basic Medicine, Guangzhou Medical University, Guangzhou, China.

Chronic pain can cause both hyperalgesia and anxiety symptoms. However, 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 how the two components are encoded. 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 the PrL-BLA circuit reversed anxiety-like behaviors, whereas activation of the PrL-l/vlPAG circuit attenuated hyperalgesia in mice with chronic pain. Moreover, mechanistic studies indicated that elevated TNF-α/TNFR1 signaling in the PrL caused increased insertion of GluA1 receptors into PrLBLA neurons and contributed to anxiety-like behaviors in mice with chronic pain. Together, these results provide insights into the circuit and molecular mechanisms in the PrL for controlling pain-related hyperalgesia and anxiety-like behaviors.

UI MeSH Term Description Entries
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D006930 Hyperalgesia An increased sensation of pain or discomfort produced by minimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve. Hyperalgesia, Tactile,Hyperalgesia, Thermal,Hyperalgia,Hyperalgia, Mechanical,Hyperalgia, Primary,Hyperalgia, Secondary,Allodynia,Allodynia, Mechanical,Allodynia, Tactile,Allodynia, Thermal,Hyperalgesia, Mechanical,Hyperalgesia, Primary,Hyperalgesia, Secondary,Hyperalgesic Sensations,Mechanical Allodynia,Mechanical Hyperalgesia,Tactile Allodynia,Thermal Allodynia,Allodynias,Hyperalgesias,Hyperalgesias, Thermal,Hyperalgesic Sensation,Mechanical Hyperalgia,Mechanical Hyperalgias,Primary Hyperalgia,Primary Hyperalgias,Secondary Hyperalgia,Secondary Hyperalgias,Sensation, Hyperalgesic,Sensations, Hyperalgesic,Thermal Hyperalgesia
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001007 Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS. Angst,Anxiousness,Hypervigilance,Nervousness,Social Anxiety,Anxieties, Social,Anxiety, Social,Social Anxieties
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D059350 Chronic Pain Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain. Chronic Primary Pain,Chronic Secondary Pain,Pain, Chronic,Widespread Chronic Pain,Chronic Pain, Widespread,Pain, Chronic Primary,Pain, Chronic Secondary,Pain, Widespread Chronic,Primary Pain, Chronic,Secondary Pain, Chronic
D066272 Basolateral Nuclear Complex A set of amygdalar nuclei bordered laterally by the EXTERNAL CAPSULE and medially by the CENTRAL AMYGDALOID NUCLEUS. Amygdaloid Basolateral Complex,Basolateral Amygdala,Basolateral Amygdaloid Nucleus,Accessory Basal Amygdaloid Nucleus,Accessory Basal Nucleus,Basal Amygdaloid Nucleus,Basal Nucleus of the Amygdala,Basolateral Nuclear Group,Deep Nuclei, Amygdala,Deep Nuclei, Amygdaloid,Lateral Amygdaloid Nucleus,Lateral Nucleus of Amygdala,Lateral Principal Nucleus of Amygdala,Paralaminar Nucleus,Amygdala Deep Nuclei,Amygdala Deep Nucleus,Amygdala Lateral Nucleus,Amygdala, Basolateral,Amygdaloid Basolateral Complices,Amygdaloid Deep Nuclei,Amygdaloid Deep Nucleus,Amygdaloid Nucleus, Basal,Amygdaloid Nucleus, Basolateral,Amygdaloid Nucleus, Lateral,Basal Nucleus, Accessory,Basolateral Amygdalas,Basolateral Complex, Amygdaloid,Basolateral Nuclear Complices,Basolateral Nuclear Groups,Deep Nucleus, Amygdala,Deep Nucleus, Amygdaloid,Nuclear Complex, Basolateral,Nuclear Complices, Basolateral,Nuclear Group, Basolateral,Nuclear Groups, Basolateral,Nucleus, Accessory Basal,Nucleus, Basolateral Amygdaloid

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