<p>The neural mechanisms underlying how early-life pain leads to long-term impairments in adult social deficit remain largely elusive. Here, by establishing a juvenile inflammatory pain model in mice and employing a combination of neuromodulation techniques, we found that early-life pain experience induces a specific and enduring social deficit in adulthood. This deficit originates from a persistent excitatory/inhibitory (E/I) imbalance within the anterior cingulate cortex (ACC). Specifically, during social interaction, we observed diminished activity in ACC excitatory neurons alongside hyperfunction of inhibitory GABAergic neurons, resulting in insufficient synaptic glutamate release. Targeted metabolomics analysis further confirmed aberrant levels of glutamate and GABA within the ACC. Targeting this mechanism, we demonstrated that either enhancing ACC excitation or dampening its inhibition via optogenetic and chemogenetic manipulations effectively rescued the social deficit. Importantly, deep brain stimulation (DBS) targeting the ACC also activated excitatory neurons and successfully reversed this social deficit. This study unveils a core mechanism whereby early-life pain impairs social function by inducing a state of hypoexcitation and hyperinhibition in the ACC. Furthermore, we establish that DBS can effectively rectify this ACC imbalance, providing a novel theoretical basis and a potential translational strategy for intervening in social deficits associated with developmental trauma.</p>