Early life adversity increases risk for chronic post-traumatic pain, data from humans and rodents

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.

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Publication Details

Journal
Pain
Published
2025-06-18
DOI
https://doi.org/10.1097/j.pain.0000000000003555
Citations
2
Primary Topic
Child Abuse and Trauma
Type
article
Field-Weighted Citation Impact
4.61

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article

Early life adversity increases risk for chronic post-traumatic pain, data from humans and rodents

Jacqueline Mickelson, Jarred Lobo, Brittany E. Punches, Christopher Lewandowski et al.
2 citations
Pain
Child Abuse and Trauma
4.61
article

Early life adversity increases risk for chronic post-traumatic pain, data from humans and rodents

Jacqueline Mickelson, Jarred Lobo, Brittany E. Punches, Christopher Lewandowski, Ying Zhao, Scott L. Rauch, Tanja Jovanović, Jennifer Strafford Stevens, Laura Thi Germine, Lauren A. McKibben, Claire Pearson, John P. Haran, Stacey L. House, Phyllis L. Hendry, Karestan C. Koenen, Robert M. Domeier, Mark John Seamon, José L. Pascual, Thomas C. Neylan, Hongxia Lu, Samuel A. McLean, Steven E. Bruce, Alan B. Storrow, Ronald C. Kessler, John F. Sheridan, Sarah D. Linnstaedt, Alice Woolard, Lauren A. Hudak, Niels K. Rathlev, Kerry James Ressler, Roland C. Merchant, Francesca L. Beaudoin, Sophia Sheikh, David A. Peak, León D. Sánchez, Xinming An, Christopher W. Jones, Brian J. O’Neil, Taanvii Verma
article en
2 citations

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.

PainVol. 166(9)
University of North Carolina at Chapel Hill (US), Brigham and Women's Hospital (US), Trinity Health (US), Baystate Medical Center (US), Harvard University (US), Emory University (US), Henry Ford Health System (US), University of Massachusetts Chan Medical School (US), University of California, San Francisco (US), Wayne State University (US), Washington University in St. Louis (US), University of Missouri–St. Louis (US), Brown University (US), McLean Hospital (US), Detroit Receiving Hospital (US), The Ohio State University Wexner Medical Center (US), University of Florida (US), Massachusetts General Hospital (US), Cooper Medical School of Rowan University (US), St. John Hospital & Medical Center (US), Institute for Behavioral Medicine (US), The Ohio State University (US), University of Pennsylvania (US), Vanderbilt University Medical Center (US), Florida College (US)
Rita Allen Foundation, National Institute of Mental Health, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Peace, Justice and strong institutions
Openalex Percentile: Top 6%
Child Abuse and Trauma
4.61
DOISourceOpenAlex
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