Early life adversity increases risk for chronic post-traumatic pain, data from humans and rodents
Recommended Citation
McKibben LA, Woolard A, McLean SA, Zhao Y, Verma T, Mickelson J, Lu H, Lobo J, House SL, Beaudoin FL, An X, Stevens JS, Neylan TC, Jovanovic T, Germine LT, Rauch SL, Haran JP, Storrow AB, Lewandowski C, Hendry PL, Sheikh S, Jones CW, Punches BE, Hudak LA, Pascual JL, Seamon MJ, Pearson C, Peak DA, Merchant RC, Domeier RM, Rathlev NK, O'Neil BJ, Sanchez LD, Bruce SE, Sheridan JF, Kessler RC, Koenen KC, Ressler KJ, and Linnstaedt SD. Early life adversity increases risk for chronic post-traumatic pain, data from humans and rodents. Pain 2025;166(9):2103-2115.
Document Type
Article
Publication Date
6-18-2025
Publication Title
Pain
Abstract
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.
Medical Subject Headings
Humans; Male; Female; Animals; Adult; Chronic Pain; Rats; Adverse Childhood Experiences; Rats, Sprague-Dawley; Stress Disorders, Post-Traumatic; Middle Aged; Young Adult; Cohort Studies; Prospective Studies; Risk Factors; Adolescent
PubMed ID
40839592
ePublication
ePub ahead of print
Volume
166
Issue
9
First Page
2103
Last Page
2115
