Study Identifies Sex Differences in Functional Organization of the Brain in Chronic Pain

human brain illustration
The main goal of this study was to characterize sex differences and abnormalities in the functional segregation and integration of the whole-brain network architecture associated with chronic pain.

Patients with chronic pain have higher cross-network connectivity within the brain compared with healthy individuals, and men and women appear to have differences in brain functional organization associated with chronic pain, according to a study published in Pain.

The study included resting state functional magnetic resonance imaging data from a total of 220 participants, including 65 people with arthritis-associated chronic low back pain and 155 healthy controls. The investigators used graph theory with modular analysis to compare the groups and determine if there were any sex differences in the organization of functional brain networks.

There was a noticeable overlap in the graph partitions with major brain intrinsic systems, such as default mode and visual, central, and sensory motor modules. Compared with healthy controls, patients with chronic pain had higher cross-network connectivity. Sex-specific nodal graph metric property changes were also found, and these changes were sometimes associated with chronic pain severity.

Women had a typically higher functional segregation in both the midcingulate cortex and subgenual anterior cingulate cortex compared with men. Also, women had lower connectivity in the network with the default mode and frontoparietal modules. Likewise, men showed connectivity with the sensorimotor module.

Classification models built by the researchers on nodal graph metrics could be used to classify a person’s sex and determine if he or she had chronic pain. The accuracy rates of these models ranged between 77% and 92% (P <.001). Within-module degree models offered the best prediction accuracy for the classification between men and women and chronic pain.

Limitations of this study included the small sample size as well as the inclusion of patients with a single chronic pain condition, which may reduce the generalizability of these findings.

In spite of the study’s methodologic limitations, the investigators suggest their “findings provide a framework to understand sex differences in the brain that may reflect chronic pain.”


Fauchon C, Meunier D, Rogachov A, et al. Sex differences in brain modular organization in chronic pain. Pain. 2021;162(4):1188-1200. doi:10.1097/j.pain.0000000000002104