Cytokines, Somatosensory Functioning, and Psychological Distress in Post-Breast Cancer Surgery Pain: A longitudinal study.

Approximately 40% of breast cancer (BC) patients experience pain during a curative treatment episode. While the biological impact of surgery and adjuvant therapies is central to pain onset, patients' pain intensity and persistence are further shaped by its interplay with psychosocial factors. Here we explored cytokine levels, somatosensory functioning, and psychological distress as biomarkers for pain in BC patients at one and three months post-surgery. Specifically, we compared these factors in BC patients with and without pain at both time points and examined their associations with pain intensity and their change over time (delta pain). Thirty-seven BC patients were measured at one and three months post-surgery. Pain intensity was assessed using the Visual Analogue Scale. Fifty-six cytokines were measured using a multiplex electrochemiluminescence-based immunoassay, somatosensory functioning through quantitative sensory testing, including thermal detection and pain thresholds, conditioned pain modulation, and temporal summation, and psychological distress (i.e., pain catastrophizing, depression, anxiety, stress, resilience, positive and negative affect) using validated questionnaires. Group comparisons and correlation analyses were conducted between these biopsychosocial factors and (delta) pain intensity. Patients in the pain group displayed higher warmth detection thresholds at the tibialis anterior muscle at both time points. At three months post-surgery, nine cytokines, anxiety and pain catastrophizing were elevated in the pain group. Correlation analysis showed that seven out of the nine elevated cytokines and anxiety positively correlated with pain intensity at three months post-surgery, supporting their potential as candidate biomarkers. Furthermore, Interleukin (IL)-17f, IL-22, IL-33, and granulocyte colony-stimulating factor (at one month) and C-reactive protein (at three months post-surgery) were positively correlated with delta pain intensity. Our findings support novel cytokine candidates for future research.