Peritraumatic C-reactive protein levels predict pain outcomes following traumatic stress exposure in a sex-dependent manner
Recommended Citation
McKibben LA, Layne MN, Albertorio-Sáez LM, Zhao Y, Branham EM, House SL, Beaudoin FL, An X, Stevens JS, Neylan TC, Clifford GD, Germine LT, Bollen KA, Rauch SL, Haran JP, Storrow AB, Lewandowski C, Musey PI, Jr., Hendry PL, Sheikh S, Jones CW, Punches BE, Swor RA, Hudak LA, Pascual JL, Seamon MJ, Datner EM, Peak DA, Merchant RC, Domeier RM, Rathlev NK, O’Neil BJ, Sanchez LD, Bruce SE, Sheridan JF, Harte SE, Kessler RC, Koenen KC, Ressler KJ, McLean SA, Linnstaedt SD. Peritraumatic C-reactive protein levels predict pain outcomes following traumatic stress exposure in a sex-dependent manner. J Pain. 2026;106326.
Document Type
Article
Publication Date
9-1-2026
Publication Title
The journal of pain
Keywords
Humans, Male, C-Reactive Protein, Female, Sex Characteristics, Longitudinal Studies, Adult, Chronic Pain, Pain Measurement, Middle Aged, Biomarkers, Acute Pain
Abstract
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.
Medical Subject Headings
Humans; Male; C-Reactive Protein; Female; Sex Characteristics; Longitudinal Studies; Adult; Chronic Pain; Pain Measurement; Middle Aged; Biomarkers; Acute Pain
PubMed ID
42214575
Volume
46
First Page
106326
Last Page
106326
