Pain is an unpleasant sensory and emotional experience associated with, or similar to, actual or potential tissue damage. The long‑term existence of pain not only brings great physiological harm to patients but also causes difficult‑to‑treat neuropsychiatric distress, such as anxiety and depression. The occurrence and transmission mechanism of pain perception are not yet clear. Here, we focus on the anterior cingulate cortex (ACC), the pain‑related multi‑dimensional experience center of the brain, to discuss and summarize the current clinical pain status and pain‑related functional imaging changes of the ACC during mood disorders, as well as the latest research advances of the ACC and its related neural circuits in pain regulation and related negative emotional comorbidities in preclinical studies, to provide novel insights and deeper understanding into future pain‑related neural circuits research.