McKibben Lauren A, Woolard Alice, McLean Samuel A, Zhao Ying, Verma Taanvii, Mickelson Jacqueline, Lu Hongxia, Lobo Jarred, House Stacey L, Beaudoin Francesca L, An Xinming, Stevens Jennifer S, Neylan Thomas C, Jovanovic Tanja, Germine Laura T, Rauch Scott L, Haran John P, Storrow Alan B, Lewandowski Christopher, Hendry Phyllis L, Sheikh Sophia, Jones Christopher W, Punches Brittany E, Hudak Lauren A, Pascual Jose L, Seamon Mark J, Pearson Claire, 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, Kessler Ronald C, Koenen Karestan C, Ressler Kerry J, Linnstaedt Sarah D
Department of Anesthesiology, Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Department of Genetics, Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Pain. 2025 Jun 18. doi: 10.1097/j.pain.0000000000003555.
Traumatic stress exposures (TSEs) are common in life. Although most individuals recover after a TSE, a substantial subset develop adverse post-traumatic neuropsychiatric sequelae such as chronic post-traumatic musculoskeletal pain (CPMP). Vulnerability factors for CPMP are poorly understood, which hinders identification of high-risk individuals for targeted interventions. One known vulnerability factor for many pain types is exposure to early life adversity (ELA), but few studies have assessed whether ELA increases risk for CPMP. This study used data from the Advancing Understanding of RecOvery afteR traumA study, a prospective human cohort study of TSE survivors, to test the hypothesis that ELA increases risk for CPMP. In addition, in secondary analyses, we assessed which subtypes of ELA (including childhood bullying) were most predictive of CPMP and whether a rat ELA model consisting of neonatal limited bedding, combined with single prolonged stress (SPS) in adulthood, would accurately model human findings. In Advancing Understanding of RecOvery afteR traumA study participants (n = 2480), using multinomial logistic regression modeling of 4 identified latent pain classes, we found that ELA increased vulnerability to the high unremitting pain class (odds ratio [OR] = 1.047, P < 0.001), the moderate pain class (OR = 1.031, P < 0.001), and the moderate recovery pain class (OR = 1.018, P = 0.004), with physical abuse, emotional abuse, and bullying being the strongest predictors of high pain class assignment. Similarly, in male and female Sprague Dawley rats, in comparison with SPS alone, neonatal limited bedding combined with SPS caused increased baseline sensitivity and prolonged mechanical hypersensitivity (F(11,197) = 3.22, P < 0.001). Further studies in animals and humans are needed to understand mechanisms by which ELA confers vulnerability to CPMP.
创伤性应激暴露(TSEs)在生活中很常见。尽管大多数人在经历TSE后会恢复,但仍有相当一部分人会出现创伤后神经精神后遗症,如慢性创伤后肌肉骨骼疼痛(CPMP)。人们对CPMP的易患因素了解甚少,这阻碍了对高危个体进行有针对性干预的识别。许多疼痛类型的一个已知易患因素是早年生活逆境(ELA),但很少有研究评估ELA是否会增加CPMP的风险。本研究使用了“创伤后恢复进展研究”的数据,这是一项对TSE幸存者进行的前瞻性人类队列研究,以检验ELA会增加CPMP风险这一假设。此外,在二次分析中,我们评估了哪些ELA亚型(包括童年霸凌)最能预测CPMP,以及由新生鼠有限垫料组成的大鼠ELA模型,结合成年期单次长时间应激(SPS),是否能准确模拟人类的研究结果。在“创伤后恢复进展研究”的参与者(n = 2480)中,通过对4种已识别的潜在疼痛类别进行多项逻辑回归建模,我们发现ELA增加了对高度持续性疼痛类别(优势比[OR] = 1.047,P < 0.001)、中度疼痛类别(OR = 1.031,P < 0.001)和中度恢复性疼痛类别(OR = 1.018,P = 0.004)的易感性,身体虐待、情感虐待和霸凌是高度疼痛类别归属的最强预测因素。同样,在雄性和雌性Sprague Dawley大鼠中,与单独的SPS相比,新生鼠有限垫料与SPS相结合会导致基线敏感性增加和机械性超敏反应延长(F(11,197) = 3.22,P < 0.001)。需要在动物和人类中进行进一步研究,以了解ELA使个体易患CPMP的机制。