Ventral hippocampal CA1 modulates pain behaviors in mice with peripheral inflammation

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.

Automated summary

Chronic pain is a major global medical problem. Recent evidence suggests that the hippocampus plays a role in modulating chronic pain, but the exact mechanisms remain unknown. In this study, a neural ensemble in the ventral hippocampal CA1 region was found to respond to noxious stimuli and become hypersensitive after peripheral inflammation. Manipulating the activity of these neurons in mice induced chronic pain-like behaviors or reduced pain-related behaviors, depending on the context. Additionally, specific pathways from the ventral hippocampus to the basolateral amygdala and infralimbic cortex were found to be involved in pain modulation at different stages of chronic inflammatory pain.