Aberrant anterior insula-sensorimotor interaction modulates pain empathy in women with primary dysmenorrhea

Background: Pain empathy engages multiple neural networks. Neuroimaging research has identified anterior insula (aINS) and the sensorimotor network in processing pain empathy among women with primary dysmenorrhea (PDM). However, it remains unclear how the interaction between the two networks modulates pain empathy during menstrual pain. Methods: This case-control study included 56 women with PDM and 55 healthy controls (HCs). Participants were instructed to take functional MRI (fMRI) scans during the menstrual phase and view images depicting painful and non-painful situations to elicit empathy, as well as the short form of McGill Pain Questionnaire to elicit pain intensity. Functional connectivity (FC) analyses of the aINS-related and sensorimotor networks, and their interactions, were conducted to investigate their relationship with pain and pain empathy. Mediation analysis was performed to investigate the role of FC mediating menstrual pain and empathy. Results: PDM patients exhibited higher scores of pain empathy, which was significantly correlated with pain intensity. With comparable bilateral aINS-precentral/postcentral FC, left aINS-postcentral connectivity showed positive correlations with both pain intensity and empathy in PDM patients, whereas. the positive interaction between the left aINS- and precentral-centered networks was inversely associated with pain empathy in HCs. Furthermore, correlation and mediation analyses revealed that left aINS-right postcentral FC mediated the relationship between menstrual pain and pain empathy in PDM women. Conclusion: aINS-sensorimotor network interactions play a critical role in pain empathy, which may nonetheless engage in divergent regulatory processes under menstrual pain, shaping psychological adaptation and empathic responses.