Hippocampal volume changes across developmental periods in female migraineurs.

Brain-related plasticity can occur at a significant rate varying on the developmental period. Adolescence in particular has been identified as a period of growth and change across the structure and function of the nervous system. Notably, research has identified migraines as common in both pediatric and adult populations, but evidence suggests that the phenotype for migraines may differ in these cohorts due to the unique needs of each developmental period. Accordingly, primary aims of this study were to define hippocampal structure in females (7-27 years of age) with and without migraine, and to determine whether this differs across developmental stages (i.e., childhood, adolescence, and young adulthood). Hippocampal volume was quantified based on high-resolution structural MRI using FMRIB's Integrated Registration and Segmentation Tool. Results indicated that migraine and age may have an interactional relationship with hippocampal volume, such that, while hippocampal volumes were lower in female migraineurs (compared to age-matched controls) during childhood and adolescence, this contrast differed during young adulthood whereby hippocampal volumes were higher in migraineurs (compared to age-matched controls). Subsequent vertex analysis localized this interaction effect in hippocampal volume to displacement of the anterior hippocampus. The transition of hippocampal volume during adolescent development in migraineurs suggests that hippocampal plasticity may dynamically reflect components of migraine that change over the lifespan, exerting possible altered responsivity to stress related to migraine attacks thus having physiological expression and psychosocial impact.

Placebos in pediatrics: A cross-sectional survey investigating physicians' perspectives.

OBJECTIVE: Placebo responses are significantly higher in children than in adults, suggesting a potential underused treatment option in pediatric care. To facilitate the clinical translation of these beneficial effects, we explored physicians' current practice, opinions, knowledge, and likelihood of recommending placebos in the future. METHODS: A cross-sectional web-based survey administered by REDCap was conducted at Boston Children's Hospital between October 2021 and March 2022. Physicians (n = 1157) were invited to participate through an email containing a link to a 23-item survey designed to assess physicians' attitudes and perceptions towards the clinical use of placebo in pediatrics. RESULTS: From 207 (18%) returned surveys, 109 (9%) were fully completed. Most respondents (79%) believed that enhancing the therapeutic components that contribute to the placebo response may be a way of improving pediatric care. However, whereas most (62%) found placebo treatments permissible, only one-third reported recommending them. In pediatrics, placebos are typically introduced as a medicine that "might help" (43%). The most common treatments recommended to enhance placebo effects are physical therapy, vitamins, and over-the-counter analgesics. Physicians most frequently recommend placebos for occasional pain, headaches, and anxiety disorders. Finally, the great majority of physicians (87%) stated they would be more likely to recommend placebo treatments if there were safety and ethical guidelines for open-label placebos. CONCLUSIONS: Placebo treatments seem permissible to physicians in pediatric care, but the development of safety and ethical guidelines may be necessary before physicians systematically incorporate the benefits of the placebo effect in pediatrics.

OnabotulinumtoxinA for Pediatric Migraine.

BACKGROUND: Migraine is a painful, prevalent, and problematic condition among children. Children need access to safe and effective treatment options to alleviate the impact of this chronic condition on their wellbeing. CLINICAL IMPLICATIONS: Nurses have a crucial role in supporting patient access to BTX-A. Given the results of this and other studies demonstrating the safety and efficacy of BTX-A in children, nurses can support policy change for health plans to fund this intervention for pediatric migraineurs. Allowing children to receive the safe and effective BTX-A injections will lessen the already significant impact of chronic migraine on their physical, emotional and mental health. Nurses can also play a key role in providing education to patients regarding safe administration of BTX-A for migraine. AIM: The objective of this study was to define the experiences, effects, and clinical response of children to onabotulinumtoxinA (BTX-A) for migraine prevention. METHODS: Clinical documentation for patients aged 13-17 years presenting for BTX-A treatment for chronic migraine between 2016-2022 in a community-based specialty clinic within a large, urban, pediatric academic medical center were included. A series of one-way repeated measures (analysis of variance [ANOVA]) were conducted to compare headache frequency, severity, and duration at baseline, and following first and second injections of BTX-A. RESULTS: Of 32 eligible participants, administration of BTX-A demonstrated a decrease in headache frequency and severity. Participants reported nearly seven fewer headache days per month. Participants reported neck stiffness, fever or flu-like symptoms, fatigue, and worsening pain following BTX-A administration. CONCLUSIONS: Pediatric migraineurs need therapies that are safe, effective, and accessible. BTX-A was a safe and effective treatment for migraine among the children included in this study.

Alterations in the structure and function of the brain in adolescents with new daily persistent headache: A pilot MRI study.

OBJECTIVE: The purpose of this study was to explore brain morphological and functional connectivity alterations in adolescents with new daily persistent headache (NDPH) compared to pain-free, healthy controls. BACKGROUND: NDPH is one of the most disabling and least understood primary headache conditions. To date, no studies have considered the role of brain function and structure in pediatric patients with NDPH. METHODS: In this cross-sectional study, resting-state functional and structural images were acquired for 13 patients with NDPH (M age = 15.9, standard deviation [SD] ± 1.4) and 13 age- and sex-matched controls (M age = 16.2, SD ± 1.8) using magnetic resonance imaging. Participants were recruited from the Pediatric Headache Program at Boston Children's Hospital and from the Greater Boston area. In patients, clinical features of NDPH, including disease duration, pain intensity ratings, pain sensitivity, and functional disability were also assessed, and their associations with functional and structural brain alterations were explored. RESULTS: Compared to controls, patients with NDPH demonstrated reduced cortical thickness in the bilateral superior temporal gyrus, left superior, and middle frontal gyrus areas (p < 0.05, Monte Carlo corrected for multiple comparisons). Furthermore, reduced cortical thickness of the left superior frontal gyrus was related to elevated pain sensitivity in NDPH (r = -0.79, p = 0.006). Patients showed altered functional connectivity between regions involved in emotional and cognitive networks of pain, including the amygdala, insula, frontal regions, and cerebellar subregions. CONCLUSION: The present study provides the first preliminary evidence of functional and structural brain differences in pediatric patients with NDPH compared to controls. Identifying alterations in cortical thickness and resting-state connectivity between specific brain regions could provide characteristics of NDPH and probable mechanisms that may guide personalized therapeutic interventions.

Integrated Features for Optimizing Machine Learning Classifiers of Pediatric and Young Adults With a Post-Traumatic Headache From Healthy Controls.

Post-traumatic headache (PTH) is a challenging clinical condition to identify and treat as it integrates multiple subjectively defined symptoms with underlying physiological processes. The precise mechanisms underlying PTH are unclear, and it remains to be understood how to integrate the patient experience with underlying biology when attempting to classify persons with PTH, particularly in the pediatric setting where patient self-report may be highly variable. The objective of this investigation was to evaluate the use of different machine learning (ML) classifiers to differentiate pediatric and young adult subjects with PTH from healthy controls using behavioral data from self-report questionnaires that reflect concussion symptoms, mental health, pain experience of the participants, and structural brain imaging from cortical and sub-cortical locations. Behavioral data, alongside brain imaging, survived data reduction methods and both contributed toward final models. Behavioral data that contributed towards the final model included both the child and parent perspective of the pain-experience. Brain imaging features produced two unique clusters that reflect regions that were previously found in mild traumatic brain injury (mTBI) and PTH. Affinity-based propagation analysis demonstrated that behavioral data remained independent relative to neuroimaging data that suggest there is a role for both behavioral and brain imaging data when attempting to classify children with PTH.

Health Mindsets in Pediatric Chronic Headache.

OBJECTIVE: Given how frequently youth with chronic headache and migraine experience setbacks in treatment, identifying factors that promote coping and resilience is critical. Mindsets have gained attention as predictors of behavior and targets of intervention across contexts, including health. Health mindsets may help to explain how children with chronic pain interpret and respond to treatment. This study evaluated whether growth health mindsets might relate to adaptive outcomes in patients with chronic pediatric headache. METHODS: Participants were 88 children and adolescents (ages 10-17 years) with headache or migraine contacted following an appointment at a pediatric headache clinic, and their parent. Patients rated their beliefs about health as more fixed versus growth-oriented. They were presented with vignettes depicting hypothetical treatment setbacks and instructed to reflect upon real-life setbacks. Patients completed questionnaires about their cognitive appraisals of setbacks, coping, quality of life, life satisfaction, and functional impairment. RESULTS: The higher children rated their growth health mindsets, the less likely they were to appraise setbacks as threatening and endorse quality-of-life problems. Children with higher growth mindsets reported higher life satisfaction and lower functional disability. There was also an indirect relation between children's mindsets and coping through cognitive appraisals of setbacks as a threat, but not challenge. CONCLUSION: This research extends the health mindsets literature by contributing preliminary evidence of health mindsets as tied to adaptive outcomes in youth with chronic headache. These findings may be of interest to clinicians and parents, as health mindsets may offer an avenue by which resilience is promoted and maladaptive appraisals are minimized.

Evidence of Chronic Complement Activation in Asymptomatic Pediatric Brain Injury Patients: A Pilot Study.

Physical insult from a mild Traumatic Brain Injury (mTBI) leads to changes in blood flow in the brain and measurable changes in white matter, suggesting a physiological basis for chronic symptom presentation. Post-traumatic headache (PTH) is frequently reported by persons after an mTBI that may persist beyond the acute period (>3 months). It remains unclear whether ongoing inflammation may contribute to the clinical trajectory of PTH. We recruited a cohort of pediatric subjects with PTH who had an acute or a persistent clinical trajectory, each around the 3-month post-injury time point, as well as a group of age and sex-matched healthy controls. We collected salivary markers of mRNA expression as well as brain imaging and psychological testing. The persistent PTH group showed the highest levels of psychological burden and pain symptom reporting. Our data suggest that the acute and persistent PTH cohort had elevated levels of complement factors relative to healthy controls. The greatest change in mRNA expression was found in the acute-PTH cohort wherein the complement cascade and markers of vascular health showed a prominent role for C1Q in PTH pathophysiology. These findings (1) underscore a prolonged engagement of what is normally a healthy response and (2) show that a persistent PTH symptom trajectory may parallel a poorly regulated inflammatory response.

Biological laterality and peripheral nerve DTI metrics.

BACKGROUND AND PURPOSE: Clinical comparisons do not usually take laterality into account and thus may report erroneous or misleading data. The concept of laterality, well evaluated in brain and motor systems, may also apply at the level of peripheral nerves. Therefore, we sought to evaluate the extent to which we could observe an effect of laterality in MRI-collected white matter indices of the sciatic nerve and its two branches (tibial and fibular). MATERIALS AND METHODS: We enrolled 17 healthy persons and performed peripheral nerve diffusion weighted imaging (DWI) and magnetization transfer imaging (MTI) of the sciatic, tibial and fibular nerve. Participants were scanned bilaterally, and findings were divided into ipsilateral and contralateral nerve fibers relative to self-reporting of hand dominance. Generalized estimating equation modeling was used to evaluate nerve fiber differences between ipsilateral and contralateral legs while controlling for confounding variables. All findings controlled for age, sex and number of scans performed. RESULTS: A main effect of laterality was found in radial, axial, and mean diffusivity for the tibial nerve. Axial diffusivity was found to be lateralized in the sciatic nerve. When evaluating mean MTR, a main effect of laterality was found for each nerve division. A main effect of sex was found in the tibial and fibular nerve fiber bundles. CONCLUSION: For the evaluation of nerve measures using DWI and MTI, in either healthy or disease states, consideration of underlying biological metrics of laterality in peripheral nerve fiber characteristics need to considered for data analysis. Integrating knowledge regarding biological laterality of peripheral nerve microstructure may be applied to improve how we diagnosis pain disorders, how we track patients' recovery and how we forecast pain chronification.

DTI and MTR Measures of Nerve Fiber Integrity in Pediatric Patients With Ankle Injury.

Acute peripheral nerve injury can lead to chronic neuropathic pain. Having a standardized, non-invasive method to evaluate pathological changes in a nerve following nerve injury would help with diagnostic and therapeutic assessments or interventions. The accurate evaluation of nerve fiber integrity after injury may provide insight into the extent of pathology and a patient's level of self-reported pain. The aim of this investigation was to evaluate the extent to which peripheral nerve integrity could be evaluated in an acute ankle injury cohort and how markers of nerve fiber integrity correlate with self-reported pain levels in afferent nerves. We recruited 39 pediatric participants with clinically defined neuropathic pain within 3 months of an ankle injury and 16 healthy controls. Participants underwent peripheral nerve MRI using diffusion tensor (DTI) and magnetization transfer imaging (MTI) of their injured and non-injured ankles. The imaging window was focused on the branching point of the sciatic nerve into the tibial and fibular division. Each participant completed the Pain Detection Questionnaire (PDQ). Findings demonstrated group differences in DTI and MTI in the sciatic, tibial and fibular nerve in the injured ankle relative to healthy control and contralateral non-injured nerve fibers. Only AD and RD from the injured fibular nerve correlated with PDQ scores which coincides with the inversion-dominant nature of this particular ankle injuruy cohort. Exploratory analyses highlight the potential remodeling stages of nerve injury from neuropathic pain. Future research should emphasize sub-acute time frames of injury to capture post-injury inflammation and nerve fiber recovery.

Pediatric Episodic Migraine with Aura: A Unique Entity?

Migraine headache is a common cause of pain and disability in children and adolescents and is a major contributor to frequently missed school days and limitations in activities. Of children and adolescents with migraine headache, approximately one-third have migraine with aura (MA). MA is often considered to be similar to migraine without aura (MO), and thus, many studies do not stratify patients based on the presence of aura. Because of this, treatment recommendations are often analogous between MA and MO, with a few notable exceptions. The purpose of this review is to highlight the current evidence demonstrating the unique pathophysiology, clinical characteristics, differential diagnosis, co-morbidities, and treatment recommendations and responses for pediatric MA.

From One Pain to Many: The Emergence of Overlapping Pains in Children and Adolescents.

OBJECTIVES: The objective of this study was to compare children and adolescents with overlapping chronic pains (OCP) to those with single chronic pains (SCP) among youth presenting in specialized clinical settings, in an effort to identify potential risk factors for developing overlapping pains. METHODS: A total of 1235 youth ages 8 to 18 seen in a tertiary care multidisciplinary pain clinic or a multidisciplinary headache clinic completed self-report measures of pain, disability, psychological functioning and clinical history and characteristics at the time of initial clinic visit. Information was captured in a chronic pain data repository and accessed for the current study. RESULTS: Subsequent pain symptoms developed on average 11.9 months (SD=24.5 mo) after onset of the first pain symptom. Compared with patients with SCP, patients with OCP report more medical comorbidity, more developmental issues, and poorer current sleep and school functioning. They also scored significantly higher than patients with SCP on self-reported functional disability, pain catastrophizing, fear of pain, depression, anxiety, and psychological stress and lower quality of life (all Ps<0.001). In multivariate analysis, variables most strongly associated with presenting with OCP were age (odds ratio [OR]: 1.1, P<0.001), having a clinically significant high functional disability (OR: 1.4, P=0.3), and low quality of life (OR: 2.5, P<0.001). DISCUSSION: Given their tendency toward more psychological and medical comorbidities, patients with OCP may require more intense and diverse treatment approaches. Some early life experiences may be a risk factor for development of OCP. Longitudinal studies are needed to fully evaluate the heightened risk for OCP associated with some of these factors.

Left to themselves: Time to target chronic pain in childhood rare diseases.

BACKGROUND: Chronic pain is prevalent among patients with rare diseases (RDs). However, little is understood about how biopsychosocial mechanisms may be integrated in the unique set of clinical features and therapeutic challenges inherent in their pain conditions. METHODS: This review presents examples of major categories of RDs with particular pain conditions. In addition, we provide translational evidence on clinical and scientific rationale for psychosocially- and neurodevelopmentally-informed treatment of pain in RD patients. RESULTS: Neurobiological and functional overlap between various RD syndromes and pain states suggests amalgamation and mutual modulation of the respective conditions. Emotional sequelae could be construed as an emotional homologue of physical pain mediated via overlapping brain circuitry. Given their clearly defined genetic and molecular etiologies, RDs may serve as heuristic models for unraveling pathophysiological processes inherent in chronic pain. CONCLUSIONS: Systematic evaluation of chronic pain in patients with RD contributes to sophisticated insight into both pain and their psychosocial correlates, which could transform treatment.

Pain stickiness in pediatric complex regional pain syndrome: A role for the nucleus accumbens.

Some individuals with chronic pain experience improvement in their pain with treatment, whereas others do not. The neurobiological reason is unclear, but an understanding of brain structure and functional patterns may provide insights into pain's responsivity to treatment. In this investigation, we used magnetic resonance imaging (MRI) techniques to determine grey matter density alterations on resting functional connectivity (RFC) strengths between pain responders and nonresponders in patients with complex regional pain syndrome. Brain metrics of pediatric patients at admission to an intensive pain rehabilitative treatment program were evaluated. Pain responders reported significant pain improvement at discharge and/or follow-up whereas nonresponders reported no improvements in pain, increases in pain, or emergence of new pain symptoms. The pain (responder/nonresponder) groups were compared with pain-free healthy controls to examine predictors of pain responder status via brain metrics. Our results show: (1) on admission, pain nonresponders had decreased grey matter density (GMD) within the nucleus accumbens (NAc) and reduced RFC strength between the NAc and the dorsolateral prefrontal cortex vs. responders; (2) Connectivity strength was positively correlated with change in pain intensity from admission to discharge; (3) Compared with pain-free controls, grey matter and RFC differences emerged only among pain nonresponders; and (4) Using a discriminative model, combining GMD and RFC strengths assessed at admission showed the highest prediction estimate (87%) on potential for pain improvement, warranting testing in a de novo sample. Taken together, these results support the idea that treatment responsiveness on pain is underpinned by concurrent brain structure and resting brain activity.

Parenting, self-regulation, and treatment adherence in pediatric chronic headache: A self-determination theory perspective.

This study examined parenting factors associated with children's self-regulation and physician-rated treatment adherence using a self-determination theory framework in pediatric chronic headache. Participants were 58 children and adolescents (aged 10-17 years), who underwent initial and follow-up multidisciplinary evaluation at a headache clinic, and their mothers. Regression analyses showed that higher maternal autonomy support and structure were significantly related to children's lower treatment-related reactance and higher adherence. Maternal controllingness had associations in the opposite directions. Children's fear of pain was related to maternal controllingness. Results suggest the importance of parents' provision of clear expectations and engaging children in treatment problem-solving and decision-making.

Altered Brain Network Connectivity Underlies Persistent Post-Traumatic Headache following Mild Traumatic Brain Injury in Youth.

Post-traumatic headaches (PTHs) are associated with mild traumatic brain injuries (mTBI) and may predict the persistence of concussion symptoms. Altered brain networks implicated in brain injury and the affective components of headache-related pain may underlie the resolution of PTH. This is a hypothesis-generating investigation to evaluate the extent to which pain symptom reporting and functional brain changes are different in a cohort of young mTBI patients with resolved (PTH-R) and persistent (PTH-P) post-traumatic headache symptoms relative to healthy controls. This was a cross-sectional investigation involving 59 participants between the ages of 12-24 (PTH-P, n = 21; PTH-R, n = 18; healthy control, n = 20). Participants had no significant history of pre-existing headaches, chronic pain, or psychiatric neurological conditions. The primary outcome was resting-state functional connectivity (RS-Fc) alterations between cohorts. Secondary outcomes were self-reported pain-related symptoms. Elevated scores were reported for fear of pain in both PTH cohorts. Using a false discovery rate of p = 0.05, the PTH-P cohort showed altered connectivity relative to healthy controls in brain regions such as the frontal, temporal, and cerebellar regions, as well as sub-cortical regions including the amygdala and accumbens. The PTH-R cohort showed altered RS-Fc between cerebellar and temporal lobe sub-regions. Our results indicate that a core network of brain regions implicated in the affective pain response are functionally altered in PTH cohorts. Results should be interpreted given limitations on sample size and multiple comparisons. Despite the resolution of symptoms, persons who experience PTH may experience ongoing functional brain abnormalities, which may underlie symptom chronification.

The Impact of Sleep on Disability and School Functioning: Results From a Tertiary Pediatric Headache Center.

Pediatric headache patients often experience significant sleep disturbance, which may be a risk factor for poor physical, academic, and emotional functioning, including increased anxiety/fear. The current retrospective cohort study of a clinical sample of youth with persistent headache aimed to examine the impact of sleep on functional outcomes and to explore pain-related fear as a mediator of the association between sleep problems and functioning. A total of 109 youth (aged 7-17 years) with persistent headache presenting to a tertiary pediatric headache center (and their parents) completed measures of sleep problems, fear of pain, functional disability, and school functioning at the time of an initial evaluation and 6 months later. After controlling for age and headache frequency and severity, linear regression analyses indicated that increased sleep problems at baseline were associated with increased functional disability and poorer school functioning at baseline (ß = 0.28, P = .01; ß = -0.42, P < .001, respectively). Poor sleep at baseline was associated with poorer school functioning (but not functional disability) at follow-up (ß = -0.25, P = .02). Mediation models demonstrated an indirect mediating effect of pain-related fear on the association between baseline sleep problems and follow-up functional disability (ß = 0.06, 95% confidence interval 0.01, 0.15) and between baseline sleep problems and follow-up school functioning (ß = -0.06, 95% confidence interval -0.13, -0.004). Sleep disturbance in youth with headache may be a risk factor for poor functional outcomes, both concurrently and over time, and may be explained partially through pain-related fear. Given the frequency with which pediatric headache patients experience co-occurring sleep problems, sleep should be thoroughly assessed and considered as a potential early treatment target.

Shifting brain circuits in pain chronicity.

The evaluation of brain changes to a specific pain condition in pediatric and adult patients allows for insights into potential mechanisms of pain chronicity and possibly long-term brain changes. Here we focused on the primary somatosensory system (SS) involved in pain processing, namely the ventroposterolateral thalamus (VPL) and the primary somatosensory cortex (SI). We evaluated, using MRI, three specific processes: (a) somatotopy of changes in the SS for different pain origins (viz., foot vs. arm); (b) differences in acute (ankle sprain versus complex regional pain syndrome-CRPS); and (c) differences of the effects of CRPS on SS in pediatric versus adult patients. In all cases, age- and sex-matched individuals were used as controls. Our results suggest a shift in concurrent gray matter density (GMD) and resting functional connectivity strengths (rFC) across pediatric and adult CRPS with (a) differential patterns of GMD (VPL) and rFC (SI) on SS in pediatric vs. adult patterns that are consistent with upper and lower limb somatotopical organization; and (b) widespread GMD alterations in pediatric CRPS from sensory, emotional and descending modulatory processes to more confined sensory-emotional changes in adult CRPS and rFC patterns from sensory-sensory alterations in pediatric populations to a sensory-emotional change in adult populations. These results support the idea that pediatric and adult CRPS are differentially represented and may reflect underlying differences in pain chronification across age groups that may contribute to the well-known differences between child and adult pain vulnerability and resilience.

Migraine in the Young Brain: Adolescents vs. Young Adults.

Migraine is a disease that peaks in late adolescence and early adulthood. The aim of this study was to evaluate age-related brain changes in resting state functional connectivity (rs-FC) in migraineurs vs. age-sex matched healthy controls at two developmental stages: adolescence vs. young adulthood. The effect of the disease was assessed within each developmental group and age- and sex-matched healthy controls and between developmental groups (migraine-related age effects). Globally the within group comparisons indicated more widespread abnormal rs-FC in the adolescents than in the young adults and more abnormal rs-FC associated with sensory networks in the young adults. Direct comparison of the two groups showed a number of significant changes: (1) more connectivity changes in the default mode network in the adolescents than in the young adults; (2) stronger rs-FC in the cerebellum network in the adolescents in comparison to young adults; and (3) stronger rs-FC in the executive and sensorimotor network in the young adults. The duration and frequency of the disease were differently associated with baseline intrinsic connectivity in the two groups. fMRI resting state networks demonstrate significant changes in brain function at critical time point of brain development and that potentially different treatment responsivity for the disease may result.

Design and Reporting Characteristics of Clinical Trials of Select Chronic and Recurrent Pediatric Pain Conditions: An Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks Systematic Review.

Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent pain in pediatric populations compared with adult populations; thus, data to support treatment efficacy in children are limited. This article evaluates the design features and reporting practices of RCTs for chronic and recurrent pain that are likely unique to, or particularly important in, a pediatric population to promote improvements in the evidence base for pediatric pain treatments. Areas covered include outcome measure selection and reporting and reporting of adverse events and challenges to recruitment and retention. A search of PubMed and EMBASE identified primary publications describing RCTs of treatments for select chronic and recurrent pain conditions in children or adolescents published between 2000 and 2017. Only 49% of articles identified a primary outcome measure. The primary outcome measure assessed pain intensity in 38% of the trials, specifically measure by verbal rating scale (13%), faces pain scale (11%), visual analogue scale (9%), or numeric rating scale (5%). All of the CONSORT harms reporting recommendations were fulfilled by <50% of the articles. Discussions of recruitment challenges occurred in 64% of articles that enrolled <90% of their target sample. However, discussions regarding retention challenges only occurred in 14% of trials in which withdrawal rates were >10%. The goal of this article is to promote comprehensive reporting of pediatric pain RCTs to improve the design of future trials, facilitate conduction of systematic reviews and meta-analyses, and better inform clinical practice. PERSPECTIVE: This review of chronic and recurrent pediatric pain trials demonstrates inadequacies in the reporting quality of key features specifically important to pediatric populations. It provides recommendations that address these shortcomings to promote continued efforts toward improving the quality of the design and publication of future pediatric clinical pain trials.