Women report higher pain intensity at a lower level of inflammation after knee surgery compared with men

Introduction and Objectives: We previously found that women report more pain after knee arthroscopic procedures than men. It remains unclear whether this is due to different biochemical responses or nociceptive mechanisms. Methods: We analyzed acute pain-related inflammatory markers in a clinical model of patient self-reported pain immediately after knee surgery. To simultaneously measure 92 inflammatory biomarkers, we used the proximity extension assay with the Proseek Multiplex Inflammation I panel (Olink Bioscience, Uppsala, Sweden). Knee surgery was performed under general anesthesia with propofol and remifentanil. Analgesic drugs were only administered on patient request. Results: Women were 4.9 times more likely to report moderate or severe pain than men (95% confidence interval, 1.2-19.6, P = 0.024). Patient age, preoperative pain, and surgery duration were not significant factors. We analyzed synovial fluids from 44 patients (23 women, 21 men). After false discovery rate correction, MMP-10 was the only biomarker that was higher among men (P=0.01). Linear discriminant analysis showed that 3 proteins (IL-8, CCL-4, and MCP-2) were expressed at higher levels inmen, with differences of >1 normalized protein expression. No proteins were overexpressed by >1 normalized protein expression in women. Conclusion: Acute pain after knee arthroscopy was more intense in women, but pro-inflammatory biomarkers and MMP-10 were higher in men. Further knowledge of cytokine function is required before concluding that the disparities in biomarker expression are clinically unimportant. The similar biochemical signaling between sexes suggests that central mechanisms are of greater importance in sex-specific joint pain perception.