Influence of chronotype on pain incidence during early adolescence.

ABSTRACT: During adolescence major shifts in sleep and circadian systems occur with a notable circadian phase delay. Yet, the circadian influence on pain during early adolescence is largely unknown. Using 2 years of data from the Adolescent Brain Cognitive Development study, we investigated the impact of chronotype on pain incidence, moderate-to-severe pain, and multiregion pain 1 year later in U.S. adolescents. Based on the Munich ChronoType Questionnaire, chronotype was calculated as the midpoint between sleep onset and offset on free days, corrected for sleep debt over the week. Adolescents reported pain presence over the past month, and if present, rated pain intensity (0-10 numerical rating scale; ≥ 4 defined as moderate-to-severe pain) and body site locations (Collaborative Health Outcomes Information Registry Body Map; ≥2 regions defined as multiregion pain). Three-level random intercept logistic regression models were specified for each pain outcome, adjusting for baseline sociodemographic and developmental characteristics. Among 5991 initially pain-free adolescents (mean age 12.0 years, SD 0.7), the mean chronotype was 3:59 am (SD 97 minutes), and the 1-year incidence of pain, moderate-to-severe pain, and multiregion pain was 24.4%, 15.2%, and 13.5%, respectively. Each hour later chronotype at baseline was associated with higher odds of developing any pain (odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.01, 1.11), moderate-to-severe pain (OR = 1.10, 95% CI = 1.05-1.17), and multiregion pain (OR = 1.08, 95% CI = 1.02-1.14) during 1-year follow-up. In this diverse U.S. adolescent sample, later chronotype predicted higher incidence of new-onset pain.

Pain Catastrophizing Moderates the Relationship Between Pain Sensitivity and Clinical Pain in Adolescents With Functional Abdominal Pain.

Pain catastrophizing has been linked to amplified pain sensitivity assessed using quantitative sensory testing (QST) in adults; pediatric data are limited, particularly in youth with functional abdominal pain (FAP). With increasing use of QST to evaluate somatosensory function and predict pain outcomes, we examined the associations between QST and clinical pain in adolescents with FAP and tested the moderating effects of pain catastrophizing. Seventy-seven adolescents (mean age 16.6 years, 85.7% female, 72.7% White, 90.8% non-Hispanic) who fulfilled diagnostic criteria for FAP completed QST assessment (pressure pain threshold and tolerance, heat pain threshold, conditioned pain modulation) and measures of abdominal pain intensity, pain interference, and pain catastrophizing. Adjusting for age and sex, only higher heat pain threshold was associated with higher abdominal pain intensity (Beta per 1-standard deviation = .54, P = .026). Contrary to hypothesis, for youth with higher pain catastrophizing, higher pressure pain tolerance was associated with greater abdominal pain intensity, but associations were not significant for youth with lower catastrophizing (P = .049). Similarly, for those with higher pain catastrophizing (in contrast to lower pain catastrophizing), higher pressure pain thresholds and tolerance were associated with higher pain interference (P = .039, .004, respectively). Results highlight the need to investigate the influence of pain catastrophizing on QST. PERSPECTIVE: This study demonstrated unexpected findings of pain catastrophizing moderating the relationships between pressure pain threshold and tolerance, and clinical pain in adolescents with FAP. This raised questions regarding our understanding of psychological contributions to QST findings in pediatric populations with chronic pain.

Comparing the prevalence of chronic pain in school-aged children in the United States from 2019 to 2020: a nationally representative study examining differences associated with the COVID-19 pandemic.

ABSTRACT: The coronavirus disease 19 (COVID-19) pandemic negatively affected children's health in the United States (US), with more severe disruption for marginalized groups. However, potential impact on pediatric chronic pain has not been assessed at the population level. This study aimed to (1) estimate differences in the US national prevalence of pediatric chronic pain during the first year of the COVID-19 pandemic (2020), relative to one year earlier (2019); (2) determine whether differences in prevalence varied across sociodemographic groups; and (3) explore changes in child, caregiver, and family factors associated with chronic pain prevalence. Using data of children 6 to 17 years from the National Survey of Children's Health 2019 and 2020 (n = 50,518), we compared weighted percentages of sample characteristics by year and conducted a series of directed-acyclic graph-informed survey-weighted Poisson regressions. The estimated national prevalence (95% CI) of pediatric chronic pain was 10.8% (9.9, 11.9%) in 2019, decreasing to 7.6% (6.9, 8.3%) in 2020. Contrary to hypotheses, the adjusted prevalence of chronic pain was 31% lower in 2020 than in 2019 (aPR = 0.69, 95% CI: 0.61, 0.79), adjusting for child age, sex, race or ethnicity, caregiver education, neighborhood park or playground, and census region. The 2019 to 2020 change in chronic pain prevalence was similar by age ( P = 0.34), sex ( P = 0.94), race or ethnicity ( P = 0.41), caregiver education ( P = 0.49), neighborhood park or playground ( P = 0.22), and census region ( P = 0.20). Exploratory analyses identified 3 potential contributors to the unexpected decrease in the national prevalence of pediatric chronic pain: lower prevalence of bullying, more frequent family meals, and higher family resilience.

Executive Functioning and Self-Management Processes Mediate the Relationship Between Insomnia and Pain-Related Disability.

Insomnia has been identified as a predictor of reduced benefit from cognitive-behavioral treatment (CBT) for adolescent chronic pain; however, it is not well understood how insomnia leads to reduced treatment response. The purpose of this study was to evaluate executive function and self-management processes as 2 potential mediators of the relationship between insomnia symptoms and pain-related disability outcomes from internet-delivered CBT using a single-arm clinical trial design. Eighty-five adolescents with chronic pain (77% female, ages 12-17 years) and their caregiver received an 8-week internet-delivered CBT intervention. Youth completed validated measures of insomnia symptoms, executive function, self-management processes, and pain-related disability at baseline, mid-treatment, immediate post-treatment, and 3-month follow-up. Results from multilevel structural equation modeling indicated that more severe insomnia symptoms were associated with greater problems with executive function, which, in turn, led to lower engagement in self-management processes and less improvement in pain-related disability. These findings identify 2 mediators by which higher insomnia symptoms may lead to reduced benefit from CBT intervention for chronic pain. Research is needed to understand whether psychological treatments for chronic pain may be optimized by strategies targeting insomnia, executive function, and/or engagement in self-management. This trial was registered at clinicaltrials.gov (NCT04043962). PERSPECTIVE: Our study suggests that executive functioning and self-management processes mediate the relationship between insomnia and treatment outcomes for pediatric chronic pain, highlighting the impact of insomnia on youth learning and implementation of self-management strategies and the critical need for targeted sleep interventions in this population.

Analgesic Patterns and Opioid Administration in Children Hospitalized With Acute Pancreatitis.

BACKGROUND: Pain is the most common symptom of acute pancreatitis (AP), and opioids have been utilized as the cornerstone of treatment. Despite the adverse effects of opioids, data on effective analgesia in children with AP is lacking. We aimed to evaluate analgesia prescribing patterns in pediatric AP, identify factors associated with opioid administration, and test the associations between opioid administration and hospital length of stay (LOS). METHODS: This is a retrospective cohort study of pediatric AP hospitalizations in a single institution from 2010 to 2020. Opioid administration was calculated for the first 48 hours of admission (morphine milligram equivalent; MME48). Data on multimodal analgesia [defined as the administration of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs)] during hospitalization was captured. RESULTS: The sample included 224 patients, mean age 12.0 years (standard deviation = 4.9) and 58.9% female. Median LOS was 4 days (interquartile range 2-9). Most patients (71.4%) were prescribed opioids, 77.7% acetaminophen, 40.2% NSAIDs, and 37.5% multimodal analgesia. Opioid administration decreased over the study period; in contrast, there was an increase in multimodal analgesia administration. Opioid administration did not differ by sex, age, biliary versus non-biliary etiology, or race/ethnicity. In a multivariate regression model, lower albumin values ( P < 0.01) and younger age ( P < 0.05) were significant predictors of increased LOS, while MME48 was not associated with increased LOS. CONCLUSIONS: Opioids were commonly administered; only 37.5% of children were administered multimodal analgesia during their hospitalization for AP. Opioid administration was not associated with increased LOS. Prospective studies are needed to determine optimal pain management for pediatric AP.

Household Food Insufficiency and Chronic Pain among Children in the US: A National Study.

This study aimed to determine the prevalence of pediatric chronic pain by household food sufficiency status and examine whether food insufficiency would be associated with greater risk for chronic pain. We analyzed data from the 2019-2020 National Survey of Children's Health of 48,410 children (6-17 years) in the United States. Across the sample, 26.1% (95% CI: 25.2-27.0) experienced mild food insufficiency and 5.1% (95% CI: 4.6-5.7) moderate/severe food insufficiency. The prevalence of chronic pain was higher among children with mild (13.7%) and moderate/severe food insufficiency (20.6%) relative to children in food-sufficient households (6.7%, p < 0.001). After adjusting for a priori covariates (individual: age, sex, race/ethnicity, anxiety, depression, other health conditions, adverse childhood events; household: poverty, parent education, physical and mental health; community: region of residence), multivariable logistic regression revealed that children with mild food insufficiency had 1.6 times greater odds of having chronic pain (95% CI: 1.4-1.9, p < 0.0001) and those with moderate/severe food insufficiency, 1.9 higher odds (95% CI: 1.4-2.7, p < 0.0001) relative to food-sufficient children. The dose-response relationship between food insufficiency and childhood chronic pain highlights the importance of further research to identify underlying mechanisms and evaluate the impact of food insufficiency on the onset and persistence of chronic pain across the lifespan.

The overlap of medical child abuse and central sensitization in adolescents: An exploratory qualitative study.

BACKGROUND: Both medical child abuse (MCA) and central sensitization (CS) may present in adolescents with chronic pain, disability, high healthcare utilization, and unremarkable medical evaluations. OBJECTIVE: This study aimed to identify themes in the clinical narratives of adolescents with chronic pain that may help differentiate MCA from CS. PARTICIPANTS AND SETTING: Participants were 28 adolescents (ages 13-18 years) with chronic pain referred to either the Child Abuse Pediatrics team or the Pediatric Pain Medicine team at a tertiary children's hospital between 2011 and 2019, and diagnosed with MCA or CS, respectively. METHODS: This was a qualitative, retrospective study. Qualitative themes were derived through a process of inductive content analysis utilizing open coding, grouping, and secondary review by an interdisciplinary panel of experts. The relative prevalence of each code, theme, and overarching category was examined between groups to identify areas of convergence and divergence. RESULTS: Several themes appeared to be more prevalent in the MCA group (n = 9) compared to the CS group (n = 19). These included sick identity, homeschooling, caregiver with mental health disorder, maternal catastrophizing, maternal misrepresentation, persistence in healthcare-seeking, mandated reports made, medical neglect, and unnecessary and harmful medical care. CONCLUSIONS: This exploratory work identified themes from the clinical narratives of adolescents with chronic pain that may help differentiate MCA from CS. A visual reference, two illness scripts, and management recommendations are presented to aid pediatric providers in facilitating appropriate referrals for adolescents with chronic pain and disability out of proportion to diagnostic workup.

Health-related quality of life in children with Hirschsprung disease and children with functional constipation: Parent-child variability.

BACKGROUND: Health-related quality of life (HRQOL) is an important outcome among children with Hirschsprung Disease (HD), but there are challenges in interpreting findings in previous studies owing to the choice of a comparator group and informant. We compared parent-proxy versus child self-report HRQOL in children with HD to children with functional constipation (FC) and examined predictors of HRQOL. METHODS: Data of 126 children (5-18 years, 60.3% male, HD: n = 52, FC: n = 74) were acquired from the Pediatric Colorectal and Pelvic Learning Consortium. Demographics, clinical variables, HRQOL (Pediatric Quality of Life Inventory parent-proxy; child self-report) and functional outcomes (Baylor Continence Scale, Cleveland Clinic Constipation Scoring System) were collected. RESULTS: Parent and child HRQOL was similar for both cohorts, with higher scores on physical functioning and lower scores on emotional and school functioning. For children with HD, demographics and clinical variables did not predict HRQOL in multivariable regression models. For children with FC, greater severity of constipation predicted lower HRQOL (parent-proxy: B = -2.14, p < 0.001; child: B = -1.75, p = 0.001). Parent-child agreement on HRQOL scores was poor to moderate in the HD group (intraclass correlations (ICC)=0.38-0.74), but moderate to excellent in the FC group (ICC=0.63-0.84). Furthermore, parents of children with FC and ≤10 years overestimated children's HRQOL (proportional OR 4.59 (1.63, 13.85); p = 0.004). CONCLUSION: Clinical symptoms and demographic factors did not predict HRQOL among children with HD, highlighting the need to examine other biopsychosocial factors to understand long term HRQOL. Low parent-child HRQOL agreement in children with HD demonstrates the importance of obtaining parent and child perspectives. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Prognosis study.

The impact of the COVID-19 pandemic on pain and psychological functioning in young adults with chronic pain.

ABSTRACT: Data are equivocal on the consequences of COVID-19 pandemic on pain and well-being for individuals with chronic pain. Furthermore, little is known regarding its impact on the health of young adults with chronic pain. We conducted a longitudinal study to compare pain, psychological functioning, and substance use before and during the pandemic of 196 young adults with chronic pain. Participants aged 18 to 24 years (M = 21.1 years; 79.6% females) reported on pain, anxiety, depression, and substance use before (October 2018-August 2019) and during the pandemic (October 2020-November 2020), in addition to the assessment of COVID-19 exposure and its impact. Before the pandemic, young adults experienced mild-to-moderate pain intensity (M = 3.75, SD = 2.33) and pain interference (M = 3.44, SD = 2.69). Findings were that pain intensity, pain interference, and depression symptoms remained stable during the pandemic. In contrast, anxiety symptoms increased significantly (M = 8.21, SD = 5.84 vs M = 8.89, SD = 5.95, P = 0.04). Tobacco, alcohol, and cannabis use were unchanged. Mixed linear models revealed that COVID-19 exposure and impact were not associated with changes in pain intensity or interference, with female sex associated with increased pain intensity (ß = 0.86, P = 0.02) and pain interference (ß = 0.87, P = 0.02). Our findings indicated relative stability of pain symptoms experienced by young adults with chronic pain. However, the increases in anxiety highlight the need to facilitate treatment access for mental health services to mitigate downstream impact.

Health-Related Quality of Life in Pediatric Acute Recurrent or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors.

OBJECTIVES: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL. METHODS: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment. RESULTS: The sample included 368 children (54.3% girls, mean age = 12.7years, standard deviation [SD] = 3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (M = 38.5, SD = 16.0) was demonstrated while psychosocial HRQOL (M = 49.5, SD = 10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (B = -10.28, P  < 0.001), episodic and constant abdominal pain (B = 04.66, P = 0.03; B = -13.25, P < 0.001) were associated with low physical HRQOL, after accounting for ARP/CP status, age, sex, exocrine, and endocrine disease (F [9, 271] = 8.34, P < 0.001). Borderline and clinical levels of emotional and behavioral problems (B = -10.18, P < 0.001; B = -15.98, P < 0.001), and constant pain (B = -4.46, P < 0.001) were associated with low psychosocial HRQOL (F [9, 271] = 17.18, P < 0.001). CONCLUSIONS: Findings highlight the importance of assessing HRQOL and treating pain and psychosocial problems in this vulnerable group of children.

Prescription Opioid Misuse and Sports-Related Concussion Among High School Students in the United States.

STUDY OBJECTIVE: Concussion is highly prevalent in adolescents and associated with a higher risk of substance use. With the rising use of opioids among adolescents, one form of substance use of concern is the misuse of prescription opioids. This study aimed to examine the association between a history of sports-related concussion in the past year and current prescription opioid misuse among high school students in the United States. SETTING: Secondary data analysis from the 2019 Youth Risk Behavior Survey. PARTICIPANTS: Nationally representative sample of high school students (n = 7314). DESIGN: Cross-sectional study. MAIN MEASURES: Participants were asked whether they experienced any concussions related to sports or being physically active during the past 12 months and whether they had any prescription opioid misuse within the past 30 days. RESULTS: Among this cohort, 14.0% reported sustaining a concussion in the past 12 months and 6% reported current prescription opioid misuse. The prevalence of prescription opioid misuse was higher among those with a history of concussion (9.9%) than among those without concussion (5.5%, P = .002). Controlling for covariates (sex, race/ethnicity, other substance use, depressive symptoms), the odds of prescription opioid misuse was 1.5 times higher for adolescents with concussion than those without (adjusted odds ratios [aOR] = 1.5; 95% CI, 1.0-2.3; P = .029). CONCLUSION: Concussion was associated with prescription opioid misuse among the US youth, even after accounting for depressive symptoms and other substance use. Longitudinal studies are needed to test causal relationships and understand biobehavioral mechanisms that underlie associations between concussion and opioid misuse in adolescents.

Associations between insufficient sleep and prescription opioid misuse among high school students in the United States.

STUDY OBJECTIVES: The aim of this study was to estimate the association between insufficient sleep and prescription opioid misuse among US high school students. METHODS: Participants were 6,884 high school students who self-reported on sleep duration and prescription opioid misuse in the 2019 Youth Risk Behavior Survey. Sleep duration was categorized by the Youth Risk Behavior Survey according to the American Academy of Sleep Medicine guidelines as follows: recommended sleep duration (8-9 hours) vs insufficient sleep (< 8 hours). Participants also reported whether they had any prescription opioid misuse during their lifetime and whether they had prescription opioid misuse within the past 30 days. RESULTS: Most (79.4%) participants reported sleeping less than 8 hours per night. Among all youth, 12.9% reported lifetime prescription opioid misuse and 6.2% reported current prescription opioid misuse. Prevalence of both lifetime and current opioid medication misuse was higher among those also reporting insufficient sleep compared to those reporting recommended sleep duration (14.3% vs 7.7%, P < .0001 for lifetime misuse and 6.6% vs 4.3%, P = .0091 for current misuse). In multivariate models, insufficient sleep was associated with an increased odds of lifetime prescription opioid misuse (adjusted odds ratios = 1.4; 95% confidence interval, 1.1-1.2; P = .006); however, we did not find an association between sleep duration and current prescription opioid misuse in multivariate analysis. CONCLUSIONS: Sleep duration is associated with lifetime opioid misuse among US youth. Longitudinal studies are needed to test whether causal relationships exist, and to understand biobehavioral mechanisms that underlie associations between sleep deficiency and opioid misuse in adolescents. CITATION: Groenewald CB, Rabbitts JA, Tham SW, Law EF, Palermo TM. Associations between insufficient sleep and prescription opioid misuse among high school students in the United States. J Clin Sleep Med. 2021;17(11):2205-2214.

Comorbid Sleep Disturbance in Adolescents with Functional Abdominal Pain.

OBJECTIVE/BACKGROUND: Sleep disturbances have been commonly reported as comorbid in youth with pain conditions, but prior research specific to functional abdominal pain (FAP) is limited. This study describes individual factors associated with increased risk for sleep disturbance and characterizes the relationship between sleep disturbance and pain-related variables. PARTICIPANTS: Participants included 278 adolescents (age 11 to 17 years, M age = 15 years; 89% Caucasian; 65% female) with FAP. METHODS: Participants reported on sleep disturbances, abdominal pain severity, functional disability, somatic symptoms, and healthcare utilization. RESULTS: Female adolescents reported greater sleep disturbance than male adolescents (t(276) = 5.52, p < .001, Cohen's d = 0.70) and increased age was associated with greater sleep disturbance (r =.20, p =.001). In hierarchical regressions controlling for age, sex, and abdominal pain, greater sleep disturbance was significantly associated with greater functional disability (ß =.32), non-gastrointestinal somatic symptoms (ß =.35), and emergency department visits (ß =.29). CONCLUSIONS: Results suggest that sleep disturbance is common and should be assessed in youth presenting with FAP and may be a potential target for intervention.

Brief Report: Associations Between Self-injurious Behaviors and Abdominal Pain Among Individuals with ASD-Associated Disruptive Mutations.

Self-injurious behaviors (SIB) are elevated in autism spectrum disorder (ASD) and related genetic disorders, but the genetic and biological mechanisms that contribute to SIB in ASD are poorly understood. This study examined rates and predictors of SIB in 112 individuals with disruptive mutations to ASD-risk genes. Current SIB were reported in 30% of participants and associated with poorer cognitive and adaptive skills. History of severe abdominal pain predicted higher rates of SIB and SIB severity after controlling for age and adaptive behavior; individuals with a history of severe abdominal pain were eight times more likely to exhibit SIB than those with no history. Future research is needed to examine associations between genetic risk, pain, and SIB in this population.

Impaired School Functioning in Children With Chronic Pain: A National Perspective.

OBJECTIVE: The purpose of this study was to determine the association between presence of chronic pain and school functioning among school-aged children (6 to 17 y) using the most recent United States national data. MATERIALS AND METHODS: Secondary data analyses of the 2016-2017 National Survey of Children's Health. Parents (n=48,254) reported on whether their child had chronic pain over the past 12 months. Parents also reported on school functioning including (1) engagement with school, (2) number of school days missed, (3) problems at school, (4) repeating a grade, and (5) diagnosis of a learning disability. Children with chronic pain were compared with children without chronic pain using multivariate logistic regression models. We also stratified analysis according to age and sex. RESULTS: In multivariate analyses, children with pain were more likely to have low school engagement (adjusted odds ratio [OR]: 1.4, 95% confidence interval [CI]: 1.0-1.9), be chronically absent (OR: 4.2, 95% CI: 3.0-5.8), have school-related problems (OR: 1.9, 95% CI: 1.5-2.3), repeat a grade (OR: 1.4, 95% CI: 1.0-2.0), and be diagnosed with a learning disability (OR: 1.6, 95% CI: 1.1-2.5). In stratified analyses, associations between chronic pain and school measures were strongest among adolescents (15 to 17 y of age) and males. DISCUSSION: This study extends evidence linking chronic pain status to poorer school functioning in a large, national sample. Poor school functioning is a pressing public concern affecting children with chronic pain. Health care providers, educators, policymakers, and families should work together to ensure that needs are met for this vulnerable population.

The role of sleep deficiency in the trajectory of postconcussive symptoms in adolescents.

Objective: To investigate the trajectory of sleep deficiency after concussion and examine its role as a predictor of postconcussive symptoms (PCS) over 3 weeks and at 3 months post-concussion. Design: This was a prospective pilot study of 29 adolescents recruited from a pediatric Emergency Department (69% female, mean age = 14.0 years, SD = 1.8) following a concussion. Methods: Adolescents completed questionnaire assessments at baseline, Weeks 1, 2, and 3 on PCS and sleep patterns. Concurrently, adolescents also completed a daily diary and wore an actigraph continuously to monitor sleep activity. At 3 months post-concussion, adolescents repeated questionnaire measures. Results: At enrollment, 53.6% reported severe PCS, and 12% maintained severe symptoms at 3 months. Over the first 3 weeks, sleep duration and daytime sleepiness gradually declined; however, insomnia symptoms remained unchanged. After accounting for age, sex and time since concussion, greater insomnia symptoms at enrollment were associated with more severe PCS at 3 weeks and 3 months (ß = 1.17, p < .001). In contrast, sleep duration, efficiency, and waketime after sleep onset were not predictors. Conclusions: Study findings suggest that insomnia symptoms after concussion may provide a target for early intervention to reduce prolonged severity and duration of PCS.

The Use of Opioids for Treatment of Pediatric Neuropathic Pain: A Literature Review.

Pediatric neuropathic pain is caused by a spectrum of disorders that are generally challenging to treat. Many of the underlying altered neurological processes are being elucidated through mechanistic studies. Few randomized control trials have evaluated the use of opioids for the treatment of adult neuropathic pain conditions, and there have been none in pediatric populations. With sparse data to provide guidance and an incomplete understanding of the underlying mechanisms, the use of opioids remains unclear. Our clinical experience and typical risk versus benefit considerations suggest a limited, if any, role for using opioids to treat pediatric neuropathic pain. In this literature review, we review the available adult and pediatric data and provide general guidance on this subject matter.

Gastrointestinal and Psychiatric Symptoms Among Children and Adolescents With Autism Spectrum Disorder.

Individuals with autism spectrum disorder (ASD) are at heightened risk of psychiatric comorbidities across the lifespan, including elevated rates of internalizing, externalizing, and self-injurious behaviors. Identification of medical comorbidities that contribute to these concerns may elucidate mechanisms through which psychiatric concerns arise, as well as offer additional avenues for intervention. Gastrointestinal (GI) conditions are of particular interest, as they are prevalent among those with ASD, may share genetic or neurobiological etiologies with the core features of ASD, and are linked with psychiatric difficulties in the general population. In this paper, we draw on data from nearly 2,800 children and adolescents with ASD within the Simons Simplex Collection to characterize the unique contributions of (1) autism symptoms, (2) psychosocial factors (child's age, sex, verbal and nonverbal IQ, adaptive behavior, race, and household income), and (3) GI concerns with respect to multiple psychiatric outcomes. Multiple regression models revealed unique contributions of ASD symptoms and multiple psychosocial factors such as verbal IQ, adaptive behavior, and family income to internalizing, externalizing, and self-injurious behavior. In general, higher levels of psychiatric symptoms were associated with more ASD symptoms, higher verbal IQ, lower adaptive behavior skills, and lower family income. Furthermore, levels of GI symptoms accounted for unique variance in psychiatric outcomes over and above these other factors, linking increased GI problems with increased psychiatric symptoms in children with ASD. Taken together, results indicate that the presence and quantity of GI symptoms should be considered when evaluating psychiatric and behavioral concerns among children with ASD, and that treatment of GI conditions may be an important component in alleviating a broad array of mental health concerns in this group.