Topical Review: Acute and Chronic Pain Experiences in Transgender and Gender-Diverse Youth.

OBJECTIVE: To provide an overview of the existing literature on gender diversity in pediatric acute and chronic pain, propose an ecological systems model of understanding pain in transgender and gender-diverse (TGD) youth, and identify a direction for future work that will address the key knowledge gaps identified. METHODS: Relevant literature on pain and gender diversity was reviewed, drawing from adult literature where there was insufficient evidence in pediatric populations. Existing relevant models for understanding minority stress, gender and pain, and pain experiences within marginalized groups were considered with the reviewed literature to develop a pain model in TGD youth. RESULTS: While there is an abundance of literature pointing to increased risk for pain experiences amongst TGD youth, there is comparably little empirical evidence of the rates of pain amongst TGD youth, prevalence of TGD identities in pain care settings, effective pain treatments for TGD youth and unique considerations for their care, and the role intersectional factors in understanding TGD youth identities and pain. CONCLUSION: Pediatric psychologists are well-positioned to advance the research on acute and chronic pain in TGD youth, make evidence-based adaptations to clinical care for TGD youth with pain, including pain related to gender affirmation, and support colleagues within the medical system to provide more inclusive care.

Long-term Pain Symptomatology in PICU Survivors Aged 8-18 Years.

BACKGROUND AND OBJECTIVES: Children discharged from the PICU often experience long-term physical, psychological, social and cognitive challenges, described as postintensive care syndrome. This study fills a critical gap by describing the long-term pain symptoms many children experience using child self-report. METHODS: Participants in this cross-sectional study were children aged 8 to 18 years (and 1 parent, n = 64 dyads) who were 8 to 24 months post-PICU discharge. Participants completed measures assessing pain, psychosocial function, and treatment utilization. Health information relevant to the PICU admission was obtained from the electronic medical record. RESULTS: Children were an average age of 14.3 years and 50% female. Average pain intensity in the past month was 3.65 (0-10 numeric rating scale), with 36% of children reporting pain ≥2 to 3 days a week. Youth with higher intensity (≥4) and more frequent pain (≥2-3 days a week) had greater pain catastrophizing, pain-related fear, anxiety, and sleep disturbance than those with less frequent and intense pain. Higher pain frequency was also associated with greater pain-related disability and depressive symptoms. Pain was not associated with any PICU-related variables abstracted from the electronic medical record. Parents reported children frequently accessed pain treatment services postdischarge; however, 37.5% reported the coronavirus disease 2019 pandemic impacted access to recommended services. CONCLUSIONS: A significant portion of children experience pain post-PICU discharge. For many of these children, pain is frequent and is associated with impairments in psychosocial function. Future prospective research studies can be used to identify risk factors of poor pain outcomes so children can receive targeted interventions.

Associations between Chronic Pain and Attention-Deficit Hyperactivity Disorder (ADHD) in Youth: A Scoping Review.

Background: Chronic pain and ADHD are common conditions among youth that negatively impact functioning. This review fills a critical gap by summarizing current research on chronic pain and ADHD comorbidity, and it proposes a conceptual model of shared associations and underlying mechanisms. Objective: The aims of the current study were to: (1) review the extant literature and present estimates of the prevalence of comorbid non-headache chronic pain and ADHD in youth and (2) describe potential shared mechanisms for ADHD and chronic non-headache pain in youth. We also outline future directions to inform future research and interventions directed to youth with comorbid pain and ADHD. Design: A scoping review of the literature was performed in MEDLINE, PsycInfo, and Cochrane Database of Systematic Reviews using a wide range of search terms related to pain, Attention Deficit-Hyperactivity Disorder, childhood, adolescence, and young adulthood. Results: Eleven published studies were included in the review. These studies examined the prevalence of chronic pain among youth with ADHD, the prevalence of ADHD in chronic pain samples, and the association between chronic pain and ADHD among youth. Findings revealed results from studies indicating a higher prevalence of ADHD among youth with chronic pain and a higher prevalence of chronic pain in samples of youth with ADHD. Conclusions: Findings from this scoping review suggest an association between chronic pain and ADHD among youth. Little research was found to examine the etiology of this association. Future studies should examine underlying mechanisms of comorbid chronic pain and ADHD.

Clinical and Demographic Factors Associated with Receiving an Opioid Prescription following Admission to the Pediatric Intensive Care Unit.

Opioids are commonly used to treat pain in the pediatric intensive care unit (PICU), and many children receive opioid prescription(s) at discharge. The frequency of opioid prescriptions at discharge and associations with individual characteristics and clinical factors are unknown. This study aimed to identify (1) the number of children who receive an opioid prescription at PICU discharge and (2) the demographic and clinical factors associated with receiving an opioid prescription. Data were collected via the electronic medical record. The sample was 3345 children (birth to 18 years) admitted to the PICU and discharged to home or an inpatient rehabilitation setting. In total, 23.7% of children were prescribed an opioid at discharge. There were group differences in who received opioid prescriptions (yes/no) related to PICU diagnosis, length of hospital stay, number of days on mechanical ventilation, number of previous hospitalizations, organ dysfunction score, and admission type (surgical versus non-surgical). Binary logistic regression models examined predictors of opioid prescription at discharge for the total sample and diagnostic subgroups. Older age and surgical admission type were the most consistent predictors of receiving an opioid prescription. Future research should examine prescription usage patterns and how use of opioids is associated with pain and functional outcomes over time.

Perceived Injustice Is Associated With Pain-related Function and Mood in Youth With Acute Musculoskeletal Pain.

OBJECTIVES: Perceived injustice (PI), which is one's appraisal of justice or fairness regarding the pain experience, is an emerging area of interest in pediatric pain research. No previous studies have investigated PI in youth with acute pain. To fill this gap, this study examined (1) associations among PI, pain-related function, and psychological function in treatment-seeking youth with acute musculoskeletal (MSK) pain, and (2) the impact of parent-child PI discordance on children's pain and psychosocial function. MATERIALS AND METHODS: Participants were youth (aged 11 to 17, 55% male) with acute pain (onset <1 mo) recruited from emergency departments or outpatient clinics and participating parents (102 parent-child dyads). Dyads completed study questionnaires within 1 month of the child's pain onset. RESULTS: Youth-reported PI was significantly correlated with poorer physical and psychosocial quality of life, higher pain catastrophizing, higher fear of pain, increased pain-related disability, and greater depression and anxiety. Furthermore, PI was significantly associated with the physical quality of life, psychosocial quality of life, and pain-related disability. Moreover, discordance in youth and parent ratings of PI was associated with children's psychological and pain-related function. Specifically, compared with Concordant dyads, youth in the Discordant dyads (youth high PI/parent low PI) reported significantly poorer physical quality of life, psychosocial quality of life, higher pain-related disability, depression, anxiety, and pain catastrophizing. DISCUSSION: These findings reveal that PI in youth with acute MSK pain is associated with quality of life and pain-related disability. Furthermore, results highlight the importance of discordance between youth and parent reports of PI on pain-related functioning.

Biomarker discovery in attention deficit hyperactivity disorder: RNA sequencing of whole blood in discordant twin and case-controlled cohorts.

BACKGROUND: A variety of DNA-based methods have been applied to identify genetic markers of attention deficit hyperactivity disorder (ADHD), but the connection to RNA-based gene expression has not been fully exploited. METHODS: Using well defined cohorts of discordant, monozygotic twins from the Michigan State University Twin Registry, and case-controlled ADHD cases in adolescents, the present studies utilized advanced single molecule RNA sequencing to identify expressed changes in whole blood RNA in ADHD. Multiple analytical strategies were employed to narrow differentially expressed RNA targets to a small set of potential biomarkers of ADHD. RESULTS: RNA markers common to both the discordant twin study and case-controlled subjects further narrowed the putative targets, some of which had been previously associated with ADHD at the DNA level. The potential role of several differentially expressed genes, including ABCB5, RGS2, GAK, GIT1 and 3 members of the galactose metabolism pathway (GALE, GALT, GALK1) are substantiated by prior associations to ADHD and by established mechanistic connections to molecular pathways relevant to ADHD and behavioral control. CONCLUSIONS: The convergence of DNA, RNA, and metabolic data suggests these may be promising targets for diagnostics and therapeutics in ADHD.

Evaluation of maternal inflammation as a marker of future offspring ADHD symptoms: A prospective investigation.

Early life predictors of attention-deficit/hyperactivity disorder (ADHD) are critically needed; they could inform etiological theory and may help identify new prevention targets. The current study examined prospectively whether maternal cytokine levels during pregnancy predict offspring ADHD symptoms at age 4-6 years. Secondarily, we evaluated maternal cytokine levels as a possible common pathway through which prenatal risks exert influence on child ADHD. Data came from a sample of women recruited during the 2nd trimester of pregnancy (N = 62) and followed postnatally until children were 4-6 years old. Maternal inflammation was assessed using 3rd trimester plasma concentrations of three indicators of nuclear factor kappa B signaling: interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 which were combined into a latent variable. Mothers and teachers reported on child ADHD symptoms, negative affect, and externalizing behaviors at 48-72 months of age. Maternal inflammation in the 3rd trimester predicted ADHD symptoms when children were 4-6 years old (ß = 0.53, 95% CI = 0.154, 0.905, p = 0.006). Further, maternal inflammation mediated the effect of prenatal distress on child ADHD (ß = 0.21, 95% CI = 0.007, 0.419, p = 0.04). The inflammation effect on ADHD was not explained by concurrent child negative affect, externalizing behavior, or familial ADHD status. This is the first human study to prospectively link maternal pregnancy cytokine levels and offspring ADHD symptoms, suggesting that cytokine levels are a possible marker of ADHD risk. Results also provide new evidence that maternal prenatal inflammation may be one common pathway by which prenatal risk factors influence offspring mental health outcomes.