Ventral hippocampal CA1 modulates pain behaviors in mice with peripheral inflammation

• Published in: Cell reports (Cambridge) 2023-01, Vol.42 (1), p.112017-112017, Article 112017
• Main Authors: Shao, Shan, Zheng, Yawen, Fu, Zibing, Wang, Jiaxin, Zhang, Yu, Wang, Cheng, Qi, Xuetao, Gong, Tingting, Ma, Longyu, Lin, Xi, Yu, Haitao, Yuan, Shulu, Wan, You, Zhang, Haolin, Yi, Ming
• Format: Article
• Language: English
• Subjects: Animals; CA1; CA1 Region, Hippocampal - physiology; chemogenetics; chronic pain; Chronic Pain - metabolism; CP: Neuroscience; hippocampal circuits; Hippocampus - metabolism; Inflammation - metabolism; in vivo recording; Mice; Neural Pathways - physiology; Neurons - metabolism; optogenetics; ventral hippocampus
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112017

Chronic pain is one of the most significant medical problems throughout the world. Recent evidence has confirmed the hippocampus as an active modulator of pain chronicity, but the underlying mechanisms remain unclear. Using in vivo electrophysiology, we identify a neural ensemble in the ventral hippocampal CA1 (vCA1) that shows inhibitory responses to noxious but not innocuous stimuli. Following peripheral inflammation, this ensemble becomes responsive to innocuous stimuli, representing hypersensitivity. Mimicking the inhibition of vCA1 neurons using chemogenetics induces chronic pain-like behaviors in naive mice, whereas activating vCA1 neurons in mice with peripheral inflammation results in a reduction of pain-related behaviors. Pathway-specific manipulation of vCA1 projections to basolateral amygdala (BLA) and infralimbic cortex (IL) shows that these pathways are differentially involved in pain modulation at different temporal stages of chronic inflammatory pain. These results confirm a crucial role of the vCA1 and its circuits in modulating the development of chronic pain. [Display omitted] •A distinct subset of neurons in vCA1 shows inhibitory responses to nociceptive stimuli•vCA1 noxious-inhibited neurons respond to innocuous stimuli during pathological pain•The suppressed activity of vCA1 causally contributes to pain behaviors in chronic pain•vCA1-IL/BLA pathways are differentially involved in chronic inflammatory pain Shao et al. reveal a group of neurons in ventral CA1 (vCA1) that show inhibitory responses to noxious stimuli but respond to innocuous stimuli during peripheral inflammation. The inhibitory activity in vCA1 causally contributes to pain behaviors, suggesting a crucial role of the vCA1 in chronic pain.