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

McKibben, L. A.; Layne, M. N.; Albertorio-Saez, E. M.; Zhao, Y.; Branham, E. M.; House, S. L.; Beaudoin, F. L.; An, X.; Stevens, J. S.; Neylan, T. C.; Clifford, G. D.; Germine, L. T.; Bollen, K. A.; Rauch, S. L.; Haran, J. P.; Storrow, A. B.; Lewandowski, C.; Musey, P. I.; Hendry, P. L.; Sheikh, S.; Jones, C. W.; Punches, B. E.; Swor, R. A.; Hudak, L. A.; Pascual, J. L.; Seamon, M. J.; Datner, E. M.; Peak, D. A.; Merchant, R. C.; Domeier, R. M.; Rathlev, N. K.; O'Neil, B. J.; Sanchez, L. D.; Bruce, S. E.; Sheridan, J. F.; Harte, S. E.; Kessler, R. C.; Koenen, K. C.; Ressler, K. J.; McLean, S.

2024-12-05 pain medicine
10.1101/2024.12.03.24318221 medRxiv
Show abstract

BackgroundChronic pain following traumatic stress exposure (TSE) is common. Increasing evidence suggests inflammatory/immune mechanisms are induced by TSE, play a key role in the recovery process versus development of post-TSE chronic pain, and are sex specific. In this study, we tested the hypothesis that the inflammatory marker C-reactive protein (CRP) is associated with chronic pain after TSE in a sex-specific manner. MethodsWe utilized blood-plasma samples and pain questionnaire data from men (n=99) and (n=223) women enrolled in AURORA, a multi-site emergency department (ED)-based longitudinal study of TSE survivors. We measured CRP using Ella/ELISA from plasma samples collected in the ED ( peritraumatic CRP, n=322) and six months following TSE (n=322). Repeated measures mixed-effects models were used to assess the relationship between peritraumatic CRP and post-TSE chronic pain. ResultsPeritraumatic CRP levels significantly predicted post-TSE chronic pain, such that higher levels of CRP were associated with lower levels of pain over time following TSE, but only in men (men:{beta}=-0.24, p=0.037; women:{beta}=0.05, p=0.470). By six months, circulating CRP levels had decreased by more than half in men, but maintained similar levels in women (t(290)=1.926, p=0.055). More men with a decrease in CRP levels had decreasing pain over time versus women (men:83% women:65%; Z=2.21, p=0.027). ConclusionsIn men but not women, we found circulating peritraumatic CRP levels predict chronic pain outcomes following TSE and resolution of CRP levels in men over time might be associated with increased pain recovery. Further studies are needed to validate these results. SummaryPeritraumatic circulating CRP levels predicted pain recovery in men following TSE and decreases in CRP levels over time were greater in men compared to women.

Published in The Journal of Pain (predicted rank #2) · training set

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