McKibben Lauren A, Layne Miranda N, Albertorio-Sáez Liz Marie, Zhao Ying, Branham Erica M, House Stacey L, Beaudoin Francesca L, An Xinming, Stevens Jennifer S, Neylan Thomas C, Clifford Gari D, Germine Laura T, Bollen Kenneth A, Rauch Scott L, Haran John P, Storrow Alan B, Lewandowski Christopher, Musey Paul I, Hendry Phyllis L, Sheikh Sophia, Jones Christopher W, Punches Brittany E, Swor Robert A, Hudak Lauren A, Pascual Jose L, Seamon Mark J, Datner Elizabeth M, Peak David A, Merchant Roland C, Domeier Robert M, Rathlev Niels K, O'Neil Brian J, Sanchez Leon D, Bruce Steven E, Sheridan John F, Harte Steven E, Kessler Ronald C, Koenen Karestan C, Ressler Kerry J, McLean Samuel A, Linnstaedt Sarah D
Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27559, USA.
Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27559, USA.
medRxiv. 2024 Dec 7:2024.12.03.24318221. doi: 10.1101/2024.12.03.24318221.
Chronic 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.
We utilized blood-plasma samples and pain questionnaire data from men (n=99) and (n=223) women enrolled in , 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.
Peritraumatic 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:β=-0.24, =0.037; women:β=0.05, =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, =0.055). More men with a decrease in CRP levels had decreasing pain over time versus women (men:83% women:65%; Z=2.21, =0.027).
In 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.
创伤性应激暴露（TSE）后慢性疼痛很常见。越来越多的证据表明，TSE可诱导炎症/免疫机制，在TSE后慢性疼痛的恢复过程与发展中起关键作用，且具有性别特异性。在本研究中，我们检验了炎症标志物C反应蛋白（CRP）以性别特异性方式与TSE后慢性疼痛相关的假设。
我们利用了参与一项基于多地点急诊科（ED）的TSE幸存者纵向研究的男性（n = 99）和女性（n = 223）的血浆样本及疼痛问卷数据。我们使用Ella/ELISA从在急诊科采集的血浆样本（“创伤周围CRP”，n = 322）以及TSE后6个月（n = 322）测量CRP。采用重复测量混合效应模型来评估创伤周围CRP与TSE后慢性疼痛之间的关系。
创伤周围CRP水平显著预测了TSE后慢性疼痛，即随着时间推移，较高的CRP水平与较低的疼痛水平相关，但仅在男性中如此（男性：β = -0.24，P = 0.037；女性：β = 0.05，P = 0.470）。到6个月时，男性循环CRP水平下降了一半以上，而女性则维持相似水平（t(290) = 1.926，P = 0.055）。随着时间推移，CRP水平下降的男性中疼痛减轻的比例高于女性（男性：83%；女性：65%；Z = 2.21，P = 0.027）。
我们发现，在男性而非女性中，循环创伤周围CRP水平可预测TSE后的慢性疼痛结果，且男性CRP水平随时间的下降可能与疼痛恢复增加有关。需要进一步研究来验证这些结果。
