AbstractWe investigated the neural correlates for chronic cancer pain conditions by retrospectively analyzing whole brain regions on 18F-fluoro-2-deoxyglucose-positron emission tomography images acquired from 80 patients with head and neck squamous cell carcinoma and esophageal cancer. The patients were divided into three groups according to perceived pain severity and type of analgesic treatment, namely patients not under analgesic treatment because of no or minor pain, patients with good pain control under analgesic treatment, and patients with poor pain control despite analgesic treatment. Uncontrollable cancer pain enhanced the activity of the hippocampus, amygdala, inferior temporal gyrus, and temporal pole. Metabolic connectivity analysis further showed that amygdala co-activation with the hippocampus was reduced in the group with poor pain control and preserved in the groups with no or minor pain and good pain control. The increased although imbalanced activity of the medial temporal regions may represent poor pain control in patients with cancer. The number of patients who used anxiolytics was higher in the group with poor pain control, whereas the usage rates were comparable between the other two groups. Therefore, further studies should investigate the relationship between psychological conditions and pain in patients with cancer and analyze the resultant brain activity.Trial registration: This study was registered at clinicaltrials.gov on 9/3/20 (NCT04537845).