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Baseline Inflammatory Cytokines Moderate Associations Between Intraoperative Oxidative Stress and Chronic
Shravani Durbhakula1, Fenan S Rassu2, Frederic T Billings Th1
1Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA.
Purpose:
A substantial proportion of patients experience chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA); yet, factors contributing to CPSP remain poorly defined, limiting mechanism-based treatments. Although perioperative oxidative stress (OS) has been associated with CPSP, it is unknown whether baseline cytokine levels, which affect nociceptor sensitization, modify the impact of OS on long term post-TKA pain outcomes.
Methods:
This exploratory secondary analysis included 58 adults undergoing unilateral primary total knee arthroplasty. Pre-incision, baseline plasma interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-10 (IL-10) were measured. Intraoperative OS was measured by quantifying plasma concentrations of F2-isoprostanes and isofurans across three intraoperative time points. Six-month post-TKA outcomes included numeric rating scale (NRS) pain intensity, Short Form McGill Pain Questionnaire 2 (MPQ-2), PROMIS Pain Interference, and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement.
Results:
Baseline cytokines were positively correlated with intraoperative OS. Hierarchical regressions indicated that IL-6 positively modified the effect of OS on average 6-month NRS pain intensity, and TNF-α and IL-10 positively modified the effect of OS on the MPQ-2 Neuropathic subscale. Simple effect analyses indicated in each case that higher intraoperative OS was associated with worse pain among participants with higher baseline cytokine levels, with no association observed at lower cytokine levels.
Conclusion:
Increased baseline inflammatory cytokine levels increased the association between increased intraoperative OS and six-month pain outcomes post-TKA, suggesting a biological "double-hit" in which inflammation and OS interact to increase CPSP vulnerability. Given the exploratory nature of these analyses, replication in larger cohorts is needed. These exploratory analyses were not corrected for multiple comparisons; therefore, findings should be interpreted as hypothesis-generating.