Uncovering brain functional connectivity disruption patterns of lung cancer-related pain

Pain is a pervasive symptom in lung cancer patients during the onset of the disease. This study aims to investigate the connectivity disruption patterns of the whole-brain functional network in lung cancer patients with cancer pain (CP+). We constructed individual whole-brain, region of interest (ROI)-level functional connectivity (FC) networks for 50 CP+ patients, 34 lung cancer patients without pain-related complaints (CP-), and 31 matched healthy controls (HC). Then, a ROI-based FC analysis was used to determine the disruptions of FC among the three groups. The relationships between aberrant FCs and clinical parameters were also characterized. The ROI-based FC analysis demonstrated that hypo-connectivity was present both in CP+ and CP- patients compared to HC, which were particularly clustered in the somatomotor and ventral attention, frontoparietal control, and default mode modules. Notably, compared to CP- patients, CP+ patients had hyper-connectivity in several brain regions mainly distributed in the somatomotor and visual modules, suggesting these abnormal FC patterns may be significant for cancer pain. Moreover, CP+ patients also showed increased intramodular and intermodular connectivity strength of the functional network, which could be replicated in cancer stage IV and lung adenocarcinoma. Finally, abnormal FCs within the prefrontal cortex and somatomotor cortex were positively correlated with pain intensity and pain duration, respectively. These findings suggested that lung cancer patients with cancer pain had disrupted connectivity in the intrinsic brain functional network, which may be the underlying neuroimaging mechanisms.