Peritraumatic C-reactive protein levels predict pain outcomes following traumatic stress exposure in a sex-dependent...

Chronic pain following traumatic stress exposure (TSE) is common. Increasing evidence suggests inflammatory and immune mechanisms are activated following TSE, play a role in the transition from acute to chronic pain, and may differ by sex. In this study, we tested the hypothesis that elevated levels of the inflammatory marker C-reactive protein (CRP) would be associated with acute and chronic pain in a sex-specific manner. We utilized blood-plasma samples and pain questionnaire data from men (n=116) and women (n=269) enrolled in AURORA, a multi-site emergency department (ED)-based longitudinal study of TSE survivors. CRP levels were measured by ELISA using plasma samples collected in the ED ('peritraumatic CRP') and six-months following TSE. Multivariate models were used to assess the relationship between CRP and pain. Men and women reported similar acute pain levels in the ED; however, pain resolved more rapidly in men over time. Peritraumatic CRP was not associated with acute pain severity in either men or women. However, six-month CRP levels were positively associated with six-month pain severity in both men (r=0.19, p=0.089, non-significant) and women (r=0.21, p=0.0015). In men only, higher peritraumatic CRP predicted lower chronic pain severity (β=-0.36, p=0.024) whereas no association was observed in women (β=0.04, p=0.628). Among men with elevated peritraumatic CRP, decreases in CRP over time were associated with decreases in pain over time (r=-0.38, p=0.0197). These findings suggest sex-specific relationships between CRP and chronic pain following TSE and highlight inflammation as a potential mechanism contributing to differential pain recovery trajectories in men and women. PERSPECTIVE: Longitudinal CRP levels following traumatic stress exposure showed sex-dependent associations with chronic pain outcomes. Unexpectedly, higher early CRP predicted lower chronic pain severity in men, suggesting inflammatory responses may differentially influence pain recovery trajectories in men and women.