Altered metabolic connectivity between the amygdala and default mode network is related to pain perception in patients with cancer

Wen-Ying Lin, Jen-Chuen Hsieh, Ching-Chu Lu, Yumie Ono, Wen-Ying Lin, Jen-Chuen Hsieh, Ching-Chu Lu, Yumie Ono

Abstract

We 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).

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Figure 1
Figure 1
Differences in brain activities related to varying levels of perceived cancer pain (cluster corrected FWE, p < 0.05). A statistically significant main effect among the groups is shown in the bilateral amygdala (Amy) and right temporal pole (TP) (a). Representative contrast estimates and the 95% confidence interval in the left amygdala [− 26, − 2, − 20] demonstrated that glucose uptake increased in the order N, AG, and AP (b). Multiple comparisons further indicated enhanced activity within the amygdala and inhibited activity in the inferior parietal lobe, precuneus, and middle cingulate cortex in the AP group relative to the N group (c). The right TP shows increased activity in the AP group relative to the AG group (d). There are no significant activity differences between groups AG and N. AG patients with good pain control under analgesics; Amy amygdala, Ang angular gyrus, AP patients with poor pain control despite analgesic treatment, Hip hippocampus, IPL inferior parietal lobe, mCing middle cingulate gyrus, N patients not on analgesics, Prc precuneus, TP temporal pole.
Figure 2
Figure 2
Brain regions showing metabolic connectivity from the left amygdala region of interest (ROI) (a), the right amygdala ROI (b), and the right temporal pole ROI (c) within the DMN regions. The seed ROIs are shown in yellow. Red and blue regions show the areas of co-activation and -deactivation with the seed ROIs (FWE corrected, p < 0.05), respectively, based on conjugate increase or decrease in the cerebral metabolic rate of glucose. AG patients with good pain control under analgesics, Ang angular gyrus, AP patients with poor pain control despite analgesic treatments, FWE family-wise error, Hip hippocampus, IPL inferior parietal lobe, N patients without analgesics, TP temporal pole.
Figure 3
Figure 3
Brain regions showing metabolic connectivity from the left amygdala region of interest (ROI) (a) and the right amygdala ROI (b) within the CEN regions. The seed ROIs are shown in yellow. Statistically significant metabolic connectivity appeared only in the AG group from the bilateral amygdala ROIs. Only co-deactivation regions were found, which are shown in blue. AG patients with good pain control under analgesics, Ang angular gyrus, CEN central executive network, DLPFC dorsolateral prefrontal cortex, FWE family-wise error, IPL inferior parietal lobe.

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