A Pilot Study Investigating the Role of Gender in the Intergenerational Relationships between Gene Expression, Chronic Pain, and Adverse Childhood Experiences in a Clinical Sample of Youth with Chronic Pain

Abstract

Chronic pain is a highly prevalent and costly issue that often emerges during childhood or adolescence and persists into adulthood. Adverse childhood experiences (ACEs) increase risk for several adverse health conditions, including chronic pain. Recent evidence suggests that parental trauma (ACEs, post-traumatic stress disorder (PTSD) symptoms) confers risk of poor health outcomes in their children. Intergenerational relationships between parental trauma and child chronic pain may be mediated by epigenetic mechanisms. A clinical sample of youth with chronic pain and their parents completed psychometrically sound questionnaires assessing ACEs, PTSD symptoms, and chronic pain, and provided a saliva sample. These were used to investigate the intergenerational relationships between four epigenetic biomarkers (COMT, DRD2, GR, and SERT), trauma, and chronic pain. The results indicated that the significant biomarkers were dependent upon the gender of the child, wherein parental ACEs significantly correlated with changes in DRD2 expression in female children and altered COMT expression in the parents of male children. Additionally, the nature of the ACE (maltreatment vs. household dysfunction) was associated with the specific epigenetic changes. There may be different pathways through which parental ACEs confer risk for poor outcomes for males and females, highlighting the importance of child gender in future investigations.

Probiotics counteract hepatic steatosis caused by ketogenic diet and upregulate AMPK signaling in a model of infantile epilepsy

“…Reverse transcription and quantitative PCR were performed as previously described. 29 Ywhaz and CycA were used as reference genes. Primers targeting genes related to lipid metabolism and inflammasome were listed in Table S1.…”

The impact of adverse childhood experiences and posttraumatic stress symptoms on chronic pain

“…Gatchel (2004), Gatchel et al (2007), and Gatchel and Turk (2008) proposed a conceptual framework, the Biopsychosocial Model of Pain, that has been examined for the potential impact of ACEs on the development of chronic pain (Nelson et al, 2021). It is postulated that ACEs may alter the biological stress response system, resulting in allostatic overload (Christensen et al, 2021;Nelson et al, 2021). Allostatic overload refers to a cumulative physiological process in which repeated exposures to stressful events may lead to the excessive release of stress hormones over time, and maladaptive activation of the hypothalamic-pituitaryadrenal (HPA) axis, ultimately causing physical complications such as cardiovascular problems (e.g., heart rate and blood pressure), inflammation, and metabolic processes (e.g., cholesterol and insulin; Su et al, 2015).…”

“…Previous research on the relationship between ACEs and pain has suggested that childhood trauma may increase inflammation and sensitize pain pathways, thereby contributing to the onset of chronic pain and perpetuating the pain through a cycle of pain and stress (Christensen et al, 2021). However, the literature on ACEs and chronic pain has yielded inconsistent and conflicting findings.…”

Validation of the Chinese version of the adverse life experiences scale

“…Additionally, in Chinese preschool children sample, no significant gender differences were found in the influence of mothers' ACEs on children's behavioral problems ( 46 ). One possible explanation for the above disagreement is that the transmission pathways of parents' ACEs differ between boys and girls, which is supported by the study of genetic epigenetic biomarkers ( 47 ). Another explanation is that the contributions of different ACEs types in the intergenerational transmission may be not equal ( 48 ).…”