Spontaneous Pain Disrupts Ventral Hippocampal CA1-Infralimbic Cortex Connectivity and Modulates Pain Progression in Rats with Peripheral Inflammation
Longyu Ma,
Lupeng Yue,
Yuqi Zhang,
Yue Wang,
Bingxuan Han,
Shuang Cui,
Feng-Yu Liu,
You Wan,
Ming Yi
Affiliations
Longyu Ma
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, P.R. China
Lupeng Yue
CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Science, Beijing 100101, China
Yuqi Zhang
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, P.R. China
Yue Wang
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, P.R. China
Bingxuan Han
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, P.R. China
Shuang Cui
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, P.R. China
Feng-Yu Liu
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, P.R. China
You Wan
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, P.R. China; Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100083, P.R. China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China; Corresponding author
Ming Yi
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, P.R. China; Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100083, P.R. China; Corresponding author
Summary: Pain involves an intrinsically dynamic connectome characterized by fluctuating spontaneous brain activity and continuous neuroplastic changes of relevant circuits. Activity in the hippocampus-medial prefrontal cortex (mPFC) pathway has been suggested to correlate with spontaneous pain and pain chronicity, but causal evidence is lacking. Here we combine longitudinal in vivo electrophysiological recording with behavioral testing and show that persistent spontaneous pain disrupts ventral hippocampal CA1-infralimbic cortex (vCA1-IL) connectivity and hippocampal modulation of IL neuronal activity in rats with peripheral inflammation. Chemo- and optogenetic rescue of vCA1-IL dysfunction relieves spontaneous pain. Circuit-specific overexpression of brain-derived neurotrophic factor (BDNF) in vCA1-IL reverses electrophysiological changes, relieves spontaneous pain, and accelerates overall recovery from inflammatory pain. Our work identifies a neural pathway that specifically correlates with spontaneous pain and supports the significance of using a circuit dynamics-based strategy for more comprehensive understanding of circuitry mechanisms underlying chronic pain. : Ma et al. show that persistent spontaneous pain disrupts ventral hippocampal CA1-infralimbic cortex (vCA1-IL) connectivity in rats with peripheral inflammation. Genetic rescue of vCA1-IL dysfunction relieves spontaneous pain and accelerates overall pain recovery. This work identifies a neural pathway that specifically correlates with spontaneous pain. Keywords: hippocampus, prefrontal cortex, pain, electrophysiology, inflammation
