Early pain in mice causes social deficits, stimulation helps

Researchers at Xuanwu Hospital in Beijing examined how pain early in life affects adult social behavior. In a mouse model, they gave an inflammatory injection to the hind paw of pups at various ages to test timing. Later, as adults, they tested the mice for social preference. The study found that early pain can leave a lasting social deficit.

Pain timing influences deficit

Pain was induced with Complete Freund’s Adjuvant injected into one paw when mice were 10 days old, and later groups received the injection at 6, 9, 12, 15, 18, or 21 days. Mice that received the injection at 12 days or earlier developed a social deficit that lasted into adulthood. These mice showed no preference for a chamber with a stranger mouse versus an empty cage, whereas controls preferred the stranger. The effect appeared in both sexes and persisted at least until 16 weeks.

The researchers focused on the anterior cingulate cortex, a region that balances excitatory and inhibitory neurons during social approach. In pain‑exposed mice, excitatory neurons fired less and inhibitory neurons were less suppressed. The mice had fewer excitatory and more inhibitory neurons, and chemical signals such as glutamate and GABA reflected the same pattern. The imbalance suggested a hypo‑excitatory, hyper‑inhibitory state.

Reversing the imbalance

To test whether correcting the imbalance would help, the team used optogenetics, chemogenetics, and deep brain stimulation. Boosting excitatory neuron activity or dampening inhibitory activity restored normal social preference. Directly infusing glutamate‑enhancing drugs or GABA‑blocking drugs also helped, though not fully. Implanting an electrode for deep brain stimulation increased excitatory activity while only mildly activating inhibitory neurons, and when applied during testing, it reversed the social deficit. A higher stimulation level caused seizure‑like reactions in some mice.

The study shows that early pain can leave a lasting social deficit by disrupting the excitatory/inhibitory balance in the ACC. It also indicates that deep brain stimulation might be a therapeutic strategy for social problems linked to developmental trauma. However, the work was done in mice, the researchers were not blinded during testing, and the long‑term benefits of stimulation were not assessed. Caution is needed before translating the findings to humans.