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Molly C Basch,1,2 Erika T Chow,1,3 Deirdre E Logan,1,4 Neil L Schechter,4 Laura E Simons1,2,4 1Division of Pain Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 2Boston Children's Hospital, Center for Pain and the Brain, PAIN Research Group, 3Boston University School of Medicine, Boston University, 4Department of Psychiatry, Harvard Medical School, Boston, MA, USA Abstract: Functional pain syndromes (FPS) characterize a subset of individuals who experience pain and related symptoms and disability without clear structural or disease etiology. In the pediatric population, FPS hold high clinical importance due to significant prevalence rates and potential to persist into adulthood. Although extensive research has been executed to disambiguate FPS, the syndromes that fall within its spectrum remain conceptually complex and sometimes ill-defined. This paper provides an overview of available research on the classification and multifaceted etiology of FPS in youth and their effects on interpersonal, psychological, and familial function. Vital aspects of a successful multidisciplinary approach to treating this population are described; however, it is evident that future research requires more longitudinal studies. Keywords: overlapping chronic pain, functional pain, primary pain disorders, pediatrics, biopsychosocial model

An important construct in understanding pain-related disability is pain-related fear. Heightened pain-related fear may result in behavioral avoidance leading to disuse, disability, and depression; whereas confrontation of avoided activities may result in a reduction of fear over time and reengagement with activities of daily living. Although there are several measures to assess pain-related fear among adults with chronic pain, none exist for children and adolescents. The aim of the current study was to develop a new tool to assess avoidance and fear of pain with pediatric chronic pain patients: the Fear of Pain Questionnaire, child report (FOPQ-C), and Fear of Pain Questionnaire, parent proxy report (FOPQ-P). After initial pilot testing, the FOPQ-C and FOPQ-P were administered to 299 youth with chronic pain and their parents at an initial multidisciplinary pain treatment evaluation. The FOPQ demonstrated very strong internal consistency of .92 for the child and parent versions. One-month stability estimates were acceptable and suggested responsivity to change. For construct validity, the FOPQ correlated with generalized anxiety, pain catastrophizing, and somatization. Evidence of criterion-related validity was found with significant associations for the FOPQ with pain, healthcare utilization, and functional disability. These results support the FOPQ as a psychometrically sound measure. PERSPECTIVE: Pain-related fear plays an important role in relation to emotional distress and pain-related disability among children and adolescents with chronic pain. Identification of patients with high levels of fear avoidance of pain with the FOPQ will inform how to proceed with psychological and physical therapy interventions for chronic pain. [ABSTRACT FROM AUTHOR]

Abstract Background Ticks are the most important pathogen vectors in Europe. They are known to be influenced by environmental factors, but these links are usually studied at specific temporal or spatial scales. Focusing on Ixodes ricinus in Belgium, we attempt to bridge the gap between current “single-sided” studies that focus on temporal or spatial variation only. Here, spatial and temporal patterns of ticks are modelled together. Methods A multi-level analysis of the Ixodes ricinus patterns in Belgium was performed. Joint effects of weather, habitat quality and hunting on field sampled tick abundance were examined at two levels, namely, sampling level, which is associated with temporal dynamics, and site level, which is related to spatial dynamics. Independent variables were collected from standard weather station records, game management data and remote sensing-based land cover data. Results At sampling level, only a marginally significant effect of daily relative humidity and temperature on the abundance of questing nymphs was identified. Average wind speed of seven days prior to the sampling day was found important to both questing nymphs and adults. At site level, a group of landscape-level forest fragmentation indices were highlighted for both questing nymph and adult abundance, including the nearest-neighbour distance, the shape and the aggregation level of forest patches. No cross-level effects or spatial autocorrelation were found. Conclusions Nymphal and adult ticks responded differently to environmental variables at different spatial and temporal scales. Our results can advise spatio-temporal extents of environment data collection for continuing empirical investigations and potential parameters for biological tick models.

Abstract: Chronic pain is common in young people and can have a major life impact. Despite the burden of chronic pain, mechanisms underlying chronic pain development and persistence are still poorly understood. Specifically, white matter (WM) connectivity has remained largely unexplored in pediatric chronic pain. Using diffusion-weighted imaging, this study examined WM microstructure in adolescents (age M = 15.8 years, SD = 2.8 years) with chronic pain (n = 44) compared with healthy controls (n = 24). Neurite orientation dispersion and density imaging modeling was applied, and voxel-based whole-white-matter analyses were used to obtain an overview of potential alterations in youth with chronic pain and tract-specific profile analyses to evaluate microstructural profiles of tracts of interest more closely. Our main findings are that (1) youth with chronic pain showed widespread elevated orientation dispersion compared with controls in several tracts, indicative of less coherence; (2) signs of neurite density tract-profile alterations were observed in several tracts of interest, with mainly higher density levels in patients; and (3) several WM microstructural alterations were associated with pain catastrophizing in the patient group. Implicated tracts include both those connecting cortical and limbic structures (uncinate fasciculus, cingulum, anterior thalamic radiation), which were associated with pain catastrophizing, as well as sensorimotor tracts (corticospinal tract). By identifying alterations in the biologically informative WM microstructural metrics orientation dispersion and neurite density, our findings provide important and novel mechanistic insights for understanding the pathophysiology underlying chronic pain. Taken together, the data support alterations in fiber organization as a meaningful characteristic, contributing process to the chronic pain state., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Memory biases for pain-related information may contribute to the development and maintenance of chronic pain; however, evidence for when (and for whom) these biases occur is mixed. Therefore, we examined neural, stress, and psychological factors that could influence memory bias, focusing on memories that motivate disabling behaviors: pain perception, conditioned responses to threat-and-safety cues, and responses to aversive nonnoxious stimuli. Two studies were conducted with adolescents with and without chronic pain. Data from 58 participants were included in study 1 (chronic pain n = 34, pain free n = 24, mean age = 16 years), and 39 participants were included in study 2 (chronic pain n = 26, pain free n = 13, mean age = 16 years). Both studies used a threat-safety learning paradigm with memory recall (≈1 month later). Participants completed structural and functional (resting-state) magnetic resonance imaging, salivary cortisol measurements, and self-report measures. Adolescents with pain and pain-free peers consistently recalled being more afraid of safety cues (CS-) and, during heightened stress at encoding (higher cortisol levels), also reported being more afraid of threat cues (CS+). However, no memory bias was present for the emotional response to an aversive stimulus (US; loud scream) or for the recall of pain intensity. Functional connectivity of the amygdala and hippocampus with memory circuits related to the degree of memory bias, but the specific connections varied between the studies, and we observed no relationship between memory bias and brain morphology. Our findings highlight the value of considering the interaction between implicit and explicit memory systems, contributing to a more comprehensive understanding of emotional memory biases in the context of chronic pain., (Copyright © 2024 International Association for the Study of Pain.)

Objective: Virtual reality (VR) can enhance engagement in outpatient physical therapy (PT) through distraction and gamification of movement. This study assessed barriers and facilitators to VR-enhanced PT., Method: Data were collected during a feasibility trial of VR-enhanced PT for youth with chronic musculoskeletal pain. Semistructured and informal interviews were conducted with youth participants, their caregivers, and collaborating physical therapists. To analyze transcriptions, content analysis was employed in multiple rounds. Barriers and facilitators to VR implementation were coded using a deductive approach, then an inductive approach was used to identify emergent themes within each deductive code category., Results: We completed interviews with youth participants (n = 9), caregivers (n = 7), and clinician stakeholders (n = 5). Coded barriers included: (1) participant identity and self-narrative inconsistent with the intervention, (2) system-level, structural constraints of healthcare, (3) lack of guidance and leadership from clinicians around VR use, (4) research burnout, (5) expectation violation and disappointment, and (6) missing the optimal treatment window. Coded facilitators included: (1) viewing VR as a bridge to achieving treatment goals, (2) having access to resources, (3) sustained positive experience and immersion in the game, (4) alignment between identity and the intervention, and (5) champion-level collaborations., Conclusions: This study highlights the importance of considering the VR technology, person using the VR, and the context in which VR is being implemented to optimize uptake and acceptability. Adopting an implementation science lens to the field of VR for chronic pain will enhance the applicability and scale of impact., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives/purpose: Childhood cancer survival brings continued mental and physical health challenges both for the child and for the family. In this study, we investigated how parents viewed their roles in their child's health and symptom monitoring during the survivorship period., Methods: Twenty-one parents of childhood cancer survivors (n = 18 mothers; parent mage = 49.78 years, child mage = 18.50 years; range = 12-25 years), whose children were at least one year off-treatment (m = 3.67 years; SD = 2.25; various diagnoses), completed semi-structured interviews. Interviews were recorded, transcribed, and analyzed using reflexive thematic analysis., Results: Analyses generated three themes which reflect roles that parents may adopt in the context of monitoring symptoms in their childhood cancer survivor. "Vigilant Mama and Papa" (theme 1) described parents who expressed a strong sense of responsibility for protecting their child's health during survivorship resulting in careful monitoring of their child's symptoms and health. "Pragmatic Mamas and Papas" (theme 2) described parents who adopted an approach to symptom and health monitoring that emphasized moving past cancer and focusing on the future. Finally, "Encouraging Mamas and Papas" (theme 3) described parents who focused on educating and preparing their child to develop an autonomous approach to health and symptom self-monitoring as they transitioned to survivorship and adulthood., Conclusion: Parents take on varying roles in monitoring their child's symptoms and health after finishing childhood cancer treatment., Implications for Cancer Survivors: Understanding the ways in which parents continue to be involved in their child's cancer journey helps researchers develop interventions to support dyadic coping in survivorship., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pain is a common consequence of childhood cancer. While most research has examined biomedical predictors of post-cancer pain, biopsychosocial conceptualisations such as the cancer threat interpretation (CTI) model hold promise for guiding comprehensive pain management strategies. Guided by the CTI model, this cross-sectional study evaluated correlates of post-cancer pain in childhood cancer survivors including threat-related risk factors (bodily threat monitoring, fear of cancer recurrence, help-seeking) and mindsets about the body. In the preceding three months, 21.8% of the survivors reported chronic pain (>3 months), and 14.3% experienced pain most days. Greater bodily threat monitoring, more fear of cancer recurrence, and more help-seeking were associated with more pain. There was heterogeneity in the mindsets that survivors of childhood cancer hold about their bodies. Holding the mindset that the 'body is an adversary' was associated with more pain, greater bodily threat monitoring, and more fear of cancer recurrence. Holding the mindset that the 'body is responsive' was associated with less bodily threat monitoring, while the mindset that the 'body is capable' was associated with greater help-seeking. A path model demonstrated a significant combined indirect effect of the 'body is an adversary' mindset on pain through bodily threat monitoring and fear of cancer recurrence. Overall, this study supported that a sub-group of childhood cancer survivors experience persistent and interfering pain and provided cross-sectional support for threat-related correlates for pain aligning with the CTI model. Body mindsets were associated with pain and threat-related correlates and may represent a novel target to support survivors with pain. PERSPECTIVE: This article presents associations of body mindsets, threat-related risk factors, and pain in survivors of childhood cancer (aged 11-25), guided by the Cancer Threat Interpretation model. The study indicates that body mindsets may be novel targets to embed in comprehensive post-cancer pain management approaches to support young survivors with pain., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Abstract: Graded exposure treatment (GET) is a theory-driven pain treatment that aims to improve functioning by exposing patients to activities previously feared and avoided. Combining key elements of GET with acceptance-based exposure, GET Living (GL) was developed for adolescents with chronic pain (GL). Based on robust treatment effects observed in our single-case experimental design pilot trial of GL (NCT01974791), we conducted a 2-arm randomized clinical trial comparing GL with multidisciplinary pain management (MPM) comprised of cognitive behavioral therapy and physical therapy for pain management (NCT03699007). A cohort of 68 youth with chronic musculoskeletal pain (M age 14.2 years; 81% female) were randomized to GL or MPM. Owing to COVID-19 restrictions, 54% of participants received zoom video delivered care. Assessments were collected at baseline, discharge, as well as at 3-month and 6-month follow-up. Primary outcomes were self-reported pain-related fear and avoidance. Secondary outcomes were child functional disability and parent protective responses to child pain. As hypothesized, GL improved in primary and secondary outcomes at 3-month follow-up. Contrary to our superiority hypothesis, there was no significant difference between GL and MPM. Patients reported both GL and MPM (in person and video) as credible and were highly satisfied with the treatment experience. Next steps will involve examining the single-case experimental design data embedded in this trial to facilitate an understanding of individual differences in treatment responses (eg, when effects occurred, what processes changed during treatment within the treatment arm). The current findings support GET Living and MPM for youth with chronic pain., (Copyright © 2023 International Association for the Study of Pain.)

Objective: Bodily threat monitoring is a core clinical feature of Fear of cancer recurrence (FCR) and is targeted in psycho-oncology treatments, yet no comprehensive self-report measure exists. The aim of this study was the theory-informed development and initial validation of the Bodily Threat Monitoring Scale (BTMS)., Methods: Adult survivors of breast and gynaecological cancers (Study 1: N = 306, age = 37-81 years) and childhood cancer survivors (Study 2: N = 126, age = 10-25 years) completed the BTMS, designed to assess how individuals monitor for and interpret uncertain symptoms as indicating that something is wrong with their body. Participants completed measures to assess construct and criterion validity of the BTMS, and childhood cancer survivors (Study 2) completed the BTMS again 2 weeks later to assess test-retest reliability., Results: The 19-item BTMS demonstrated excellent internal consistency across adult and childhood cancer samples (α = 0.90-0.96). Factor analyses indicated two subscales capturing 1. Monitoring of bodily sensations and 2. Threatening interpretations of bodily sensations. Two-week stability estimates were acceptable. For construct validity, the BTMS correlated with body vigilance and anxiety sensitivity. The BTMS also demonstrated criterion validity, yielding significant associations with FCR, intolerance of uncertainty, help-seeking behaviours, and quality of life. The BTMS was associated with FCR while controlling for body vigilance and anxiety sensitivity, indicating a unique contribution of this theory-informed measure., Conclusions: The BTMS shows evidence of sound psychometric properties and could be used to elucidate the role of bodily threat monitoring in the maintenance and management of FCR., (© 2023 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Introduction: Neuropathic pain (NP) arises from nerve damage or disease, and when not defined, it can impair function and quality of life. Early detection allows for interventions that can enhance outcomes. Diagnosis of NP can be difficult if not properly evaluated. PainDETECT is a NP screening tool developed and successfully used in adults., Objectives: We evaluated the validity of painDETECT in a pediatric population., Methods: Adolescents and young adults (10-19 years old) completed painDETECT and quantitative sensory testing (QST), which assessed mechanical allodynia and hyperalgesia, common symptoms of NP. Pain diagnoses, including neuropathic pain (n = 10), were collected through documentation in the medical chart. Descriptive statistics were used to examine age, gender, pain diagnoses, and painDETECT scores. Kruskal-Wallis H tests were conducted to examine differences in QST results across painDETECT categorizations., Results: Youth with chronic pain (N = 110, M age = 15.08 ± 2.4 years, N female = 88) and peers without pain (N = 55, M age = 15.84 ± 3.9 years, N female = 39) completed the painDETECT. The painDETECT scores for youth with pain (M = 12.7 ± 6.76) were significantly higher than those for peers without pain (M = 2.05 ± 2.41). PainDETECT demonstrated 80% sensitivity and 33% specificity in a pediatric population. Individuals who screened positively on the PainDETECT had significantly higher mechanical allodynia (M = 0.640 ± 0.994) compared with those who screened negatively (M = 0.186 ± 0.499; P = 0.016)., Conclusion: PainDETECT demonstrated the ability to screen for NP, and QST mechanical allodynia results were consistent with a positive NP screen. Results of the study offer preliminary support for the ongoing assessment of the painDETECT as a brief, inexpensive, and simple-to-use screening tool for pediatric patients with primary pain complaints., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Chronic pain is prevalent across the life span and associated with significant individual and societal costs. Behavioral interventions are recommended as the gold-standard, evidence-based interventions for chronic pain, but barriers, such as lack of pain-trained clinicians, poor insurance coverage, and high treatment burden, limit patients' ability to access evidenced-based pain education and treatment resources. Recent advances in technology offer new opportunities to leverage innovative digital formats to overcome these barriers and dramatically increase access to high-quality, evidenced-based pain treatments for youth and adults. This scoping review highlights new advances. First, we describe system-level barriers to the broad dissemination of behavioral pain treatment. Next, we review several promising new pediatric and adult pain education and treatment technology innovations to improve access and scalability of evidence-based behavioral pain treatments. Current challenges and future research and clinical recommendations are offered., Competing Interests: BD is Chief Science Advisor at AppliedVR and she receives consulting fees for this role. BD receives royalties for four pain treatment books she has authored or coauthored. She is the principal investigator for two pain research awards from the Patient-Centered Outcomes Research Institute. BD is principal investigator for two NIH grants. BD serves on the Board of Directors for the American Academy of Pain Medicine, is on the Board of Directors for the Institute for Brain Potential, and is on the Medical Advisory Board for the Facial Pain Association. BD is a scientific member of the NIH Interagency Pain Research Coordinating Committee, a former member of the Centers for Disease Control and Prevention Opioid Workgroup (2020–2021), and a current member of the Pain Advisory Group of the American Psychological Association. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Darnall, Edwards, Courtney, Ziadni, Simons and Harrison.)

Purpose: Childhood cancer survivors report self-monitoring for and worrying about symptoms of disease recurrence and secondary cancers, although symptom-related worry is associated with poorer health-related quality of life. This survey captured pediatric oncologists' beliefs and communication practices regarding symptom self-monitoring for childhood cancer survivors., Methods: Using a closed-loop snowball sampling technique, pediatric oncologists completed an online survey regarding the importance of symptom self-monitoring for off-therapy patients, the degree to which symptom self-monitoring was perceived to cause stress and worry, and communication practices., Results: 196 pediatric oncologists (White [78%]; female [64%]; M age = 47 years) from every continent except Antarctica participated. Oncologists believed it is important for off-therapy patients to self-monitor for symptoms of cancer recurrence (90%) and treatment late effects (94%), although some noted that recurrence (30%) and late effects (55%) are typically detected by routine surveillance before symptoms appear. Oncologists varied in their beliefs that off-therapy patients do (31%) or do not (31%) worry unnecessarily about symptoms of recurrence. Two thirds (62%) of oncologists reported often/always discussing with off-therapy patients which symptoms could indicate cancer recurrence, whereas fewer than half (43%) often/always discussed which symptoms were unlikely to indicate recurrence. Oncologists identified a need for education regarding how to communicate around symptom self-monitoring and the potential utility of a screening tool to identify those who worry excessively., Conclusion: Despite nearly universal belief that their off-therapy patients should self-monitor for symptoms of disease recurrence and late effects, a substantial proportion of pediatric oncologists do not counsel patients on symptom self-monitoring. Since nearly one-third believe that off-therapy patients worry unnecessarily about symptoms of recurrence, improving patient education regarding which symptoms are and are not medically concerning could decrease stress and improve health-related quality of life for pediatric cancer survivors.

Background: Increasing the access to and improving the impact of pain treatments is of utmost importance, especially among youths with chronic pain. The engagement of patients as research partners (in contrast to research participants) provides valuable expertise to collaboratively improve treatment delivery., Objective: This study looked at a multidisciplinary exposure treatment for youths with chronic pain through the lens of patients and caregivers with the aim to explore and validate treatment change processes, prioritize and develop ideas for improvement, and identify particularly helpful treatment elements., Methods: Qualitative exit interviews were conducted with patients and caregivers at their discharge from 2 clinical trials (ClinicalTrials.gov NCT01974791 and NCT03699007). Six independent co-design meetings were held with patients and caregivers as research partners to establish a consensus within and between groups. The results were validated in a wrap-up meeting., Results: Patients and caregivers described that exposure treatment helped them better process pain-related emotions, feel empowered, and improve their relationship with each other. The research partners developed and agreed upon 12 ideas for improvement. Major recommendations include that pain exposure treatment should be disseminated more not only among patients and caregivers but also among primary care providers and the general public to facilitate an early referral for treatment. Exposure treatment should allow flexibility in terms of duration, frequency, and delivery mode. The research partners prioritized 13 helpful treatment elements. Most of the research partners agreed that future exposure treatments should continue to empower patients to choose meaningful exposure activities, break long-term goals into smaller steps, and discuss realistic expectations at discharge., Conclusions: The results of this study have the potential to contribute to the refinement of pain treatments more broadly. At their core, they suggest that pain treatments should be disseminated more, flexible, and transparent., (©Lea Schemer, Courtney W Hess, Amanda R Van Orden, Kathryn A Birnie, Lauren E Harrison, Julia A Glombiewski, Laura E Simons. Originally published in Journal of Participatory Medicine (https://jopm.jmir.org), 09.03.2023.)

Objectives: An important part of providing pain science education is to first assess baseline knowledge and beliefs about pain, thereby identifying misconceptions and establishing individually-tailored learning objectives. The Concept of Pain Inventory (COPI) was developed to support this need. This study aimed to characterize the concept of pain in care-seeking youth and their parents, to examine its clinical and demographic correlates, and to identify conceptual gaps., Materials and Methods: Following an initial interdisciplinary evaluation, a cohort of 127 youth aged 8 to 18 years, and their parents, completed a series of questionnaires., Results: Parents had slightly higher COPI scores than youth did, reflecting parents' greater alignment with contemporary pain science. The moderate positive association with older age among youth ( r =.32) suggests that COPI is sensitive to cognitive development and life experiences. Youth and parent COPI responses were weakly associated ( r =0.24), highlighting the importance of targeting the concept of pain in both groups. For both parents and youth, 'Learning about pain can help you feel less pain' was the least endorsed concept. This conceptual 'gap' is a key point of intervention that could potentially lead to greater engagement with multidisciplinary pain treatment., Discussion: The COPI appears useful for identifying conceptual gaps or 'sticking points'; this may be an important step to pre-emptively address misconceptions about pain through pain science education. Future research should determine the utility of COPI in assessing and treating youth seeking care for pain. The COPI may be a useful tool for tailoring pain science education to youth and their parents., Competing Interests: J.W.P.: receives royalties for books related to pediatric pain education. G.L.M.: received support from Reality Health, ConnectHealth UK, Kaiser Permanente, AIA Australia, Workers’ Compensation Boards, and professional sporting organizations in Australia, Europe, and South and North America. Professional and scientific bodies have reimbursed him for travel costs related to the presentation of research on pain at scientific conferences/symposia. He has received speaker fees for lectures on pain and rehabilitation. He receives royalties for books on pain and pain education. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chronic musculoskeletal (MSK) pain is a prominent health concern, resulting in pain-related disability, loss of functioning, and high health care costs. Physiotherapy rehabilitation is a gold-standard treatment for improving functioning in youth with chronic MSK pain. However, increasing physical activity can feel unattainable for many adolescents because of pain-related fear and movement avoidance. Virtual reality (VR) offers an immersive experience that can interrupt the fear-avoidance cycle and improve engagement in physiotherapy. Despite promising initial findings, data are limited and often lack the rigor required to establish VR as an evidence-based treatment for MSK pain., Objective: This trial evaluates physiorehabilitation with VR in adolescents with MSK pain. This protocol outlines the rationale, design, and implementation of a randomized controlled trial enhanced with a single-case experimental design., Methods: This study is a 2-group randomized controlled trial assessing the use of physiorehabilitation with VR in adolescents with MSK pain. The authors will collaborate with physical therapists to integrate VR into their standard clinical care. For participants enrolled in standard physiotherapy, there will be no VR integrated into their physical therapy program. Primary outcomes include physical function and engagement in VR. Secondary outcomes include pain-related fear and treatment adherence. Moreover, we will obtain clinician perspectives regarding the feasibility of integrating the intervention into the flow of clinical practice., Results: The pilot study implementing physiorehabilitation with VR demonstrated that high engagement and use of physiorehabilitation with VR were associated with improvements in pain, fear, avoidance, and function. Coupled with qualitative feedback from patients, families, and clinicians, the pilot study results provide support for this trial to evaluate physiorehabilitation with VR for youth with chronic MSK pain. Analysis of results from the main clinical trial will begin as recruitment progresses, and results are expected in early 2024., Conclusions: Significant breakthroughs for treating MSK pain require mechanistically informed innovative approaches. Physiorehabilitation with VR provides exposure to progressive challenges, real-time feedback, and reinforcement for movement and can include activities that are difficult to achieve in the real world. It has the added benefit of sustaining patient motivation and adherence while enabling clinicians to use objective benchmarks to influence progression. These findings will inform the decision of whether to proceed with a hybrid effectiveness-dissemination trial of physiorehabilitation with VR, serving as the basis for potential large-scale implementation of physiorehabilitation with VR., Trial Registration: ClinicalTrials.gov NCT04636177; https://clinicaltrials.gov/ct2/show/NCT04636177., International Registered Report Identifier (irrid): DERR1-10.2196/40705., (©Laura E Simons, Courtney W Hess, Ellison S Choate, Amanda R Van Orden, Alexandra G Tremblay-McGaw, Maria Menendez, Derek B Boothroyd, Gomathy Parvathinathan, Anya Griffin, Thomas J Caruso, Jennifer Stinson, Amy Weisman, Timothy Liu, Kurt Koeppen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.12.2022.)

Background: Endometriosis is the leading cause of chronic pelvic pain. Alterations in brain functional connectivity have been reported in adult women with endometriosis-associated pain (EAP), however, it is still unknown if similar patterns of changes exist in adolescents., Methods: In this pilot study, resting-state fMRI scans were obtained from 11 adolescent and young women with EAP and 14 healthy female controls. Using a seed-to-voxel approach, we investigated functional connectivity between the anterior insula, medial prefrontal cortex, and the rest of the brain. Furthermore, we explored whether potential functional connectivity differences were correlated with clinical characteristics including disease duration, pain intensity, and different psychosocial factors (pain catastrophizing, fear of pain, functional disability, anxiety, and depression)., Results: Our findings revealed that patients with EAP demonstrated significantly decreased connectivity between the right anterior insula and two clusters: one in the right cerebellum, and one in the left middle frontal gyrus compared to controls. Additionally, functional connectivity between the right anterior insula and the right cerebellum was positively associated with pain intensity levels. In patients with EAP, brain changes were also correlated with state anxiety and fear of pain., Conclusions: Our results are relevant not only for understanding the brain characteristics underlying EAP at a younger age, but also in enhancing future pain treatment efforts by supporting the involvement of the central nervous system in endometriosis., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Competing Interests: We declare no competing interests. This Comment was funded by the National Center for Complementary and Integrative Health (grant number NCCIH 1K23AT010643 to SN). KM is a pain advocate and a person with lived experience.

Introduction: Chronic pain affects a significant number of children and impacts multiple domains including social, emotional and behavioural functioning, and negatively impacts family functioning. Roughly 5% of youth with chronic pain experience moderate to severe pain-related disability, with pain-related fear and avoidance of activities being identified as substantial barriers to treatment engagement. Evidence supports targeted psychological and physical interventions to address these barriers (eg, graded-exposure treatment), but accessibility to intervention is undermined by a shortage of services outside of urban areas, high treatment-related costs, and long provider waitlists; highlighting the need to develop digitally delivered behavioural intervention, using agile and iterative study designs that support rapid development and timely dissemination., Methods and Analysis: This study seeks to develop an effective and scalable intervention for youth with chronic pain and their caregivers. This paper presents a user-centred protocol for the development and refinement of a digital exposure treatment for youth and caregivers, as well as the study design to examine feasibility and preliminary efficacy of the treatment using single-case experimental design (SCED). Assessments include daily diaries, completed from baseline and daily throughout the intervention (~6 weeks), and at 3-month follow-up, as well as self-report measures completed at baseline, end of intervention and 3-month follow-up. Primary outcomes include treatment satisfaction, treatment expectancy, adherence to daily dairies and functional disability. Secondary outcomes are pain-related fear and avoidance of activities, pain catastrophising and pain acceptance. We will present descriptive and model-based inference analyses, based on SCED reporting guidelines. We will calculate effect sizes for each individual on each outcome. We will examine mean treatment expectancy, credibility and satisfaction scores, and patient drop-out percentage., Ethics and Dissemination: This study is approved by the Institutional Review Board at Stanford University (protocol #53323). Findings will be actively disseminated through peer-reviewed journals, conference presentations and social media., Trial Registration Number: NCT05079984., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Current literature in pediatric pain evaluates the Fear Avoidance model (FAM) pathways at the trait (or macrotemporal) level, but it is unknown if these pathways also occur at the state (or microtemporal) level. Identifying microtemporal processes can improve our understanding of how the relationships within the Fear Avoidance constructs vary when specific Fear Avoidance variables wax and wane. We hypothesized that changes in FAM constructs would be associated with changes in the next variable in the sequence on a microtemporal level, including: (1) higher pain when there is more pain-related fear, (2) higher pain-related fear when there is more avoidance, and (3) higher avoidance when there is more reported disability., Methods: 71 pediatric patients with chronic abdominal pain ( M =13.34 y, SD=2.67 y) reported pain severity, pain-related fear, and avoidance via ecological momentary assessments over 14 days., Results: Our results indicated significant microtemporal relationships between Fear Avoidance constructs for pain predicting pain-related fear, pain-related fear predicting avoidance, and avoidance predicting disability., Discussion: The current study suggests that the ways in which the FAM is related to various aspects of pain functioning differs on a state-level, which adds new clinical and research opportunities., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Scan-related anxiety ("scanxiety") refers to the fear, stress, and anxiety in anticipation of tests and scans in follow-up cancer care. This study assessed the feasibility of Ecological Momentary Assessment (EMA) for real-world, real-time capture of scanxiety using patients' personal smartphone., Methods: Adolescent and Young Adult survivors of childhood cancer were prompted to complete EMA surveys on a smartphone app three times per day for 11 days (33 surveys total) around their routine surveillance scans. Participants provided structured feedback on the EMA protocol., Results: Thirty out of 46 contacted survivors (65%) enrolled, exceeding the preregistered feasibility cutoff of 55%. The survey completion rate (83%) greatly exceeded the preregistered feasibility cutoff of 65%. Participants generally found the smartphone app easy and enjoyable to use and reported low levels of distress from answering surveys. Participants reported significantly more daily fear of cancer recurrence (FCR) and negative affect in the days before compared to the days after surveillance scans, aligning with the expected trajectory of scanxiety. Participants who reported greater FCR and scanxiety using comprehensive measures at baseline also reported significantly more daily FCR around their surveillance scans, indicating validity of EMA items. Bodily threat monitoring was prospectively and concurrently associated with daily FCR, thus warranting further investigation as a risk factor for scanxiety., Conclusions: Findings indicate the feasibility, acceptability, and validity of EMA as a research tool to capture the dynamics and potential risk factors for scanxiety., (© 2022 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Abstract: Chronic pain is a prevalent condition in youth, and the pain experience is strongly influenced by emotional processes. Studying emotion variability and regulation (ER) may help better understand pain behavior. As the development of emotion-related abilities predominantly takes place in the family context, examining ER within parent-adolescent dyads is important. We set out to test the association of parent and adolescent ER and adolescent emotional variability with adolescent pain behavior (ie, pain interference, activity avoidance, and activity engagement). A sample of 56 adolescents (Mage = 14.5, 85.7% women) with chronic pain and one of their parents (92.9% mothers) participated in this study. Adolescents completed baseline measures of average pain intensity, ER, and mean positive and negative affect. Furthermore, adolescents completed an electronic diary for 14 consecutive days, reporting on emotional state, activity avoidance, activity engagement, and pain interference. Parents completed measures of ER and their own history of pain. We performed a variable selection procedure, the least absolute shrinkage and selection operator method, to determine important predictors of adolescent pain behavior. Adolescent high positive affect was associated with more activity engagement, less pain interference, and less activity avoidance, indicating that positive affect might enhance the willingness to engage in activities in the presence of pain. Adolescent ER strategy emotional reappraisal and parents' own history of pain were predictors of less activity engagement. Parent ER was not related to adolescent ER. In conclusion, our results highlight the potential of enhancing positive affect as an intervention target for chronic pain., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Objectives: COVID-19 abruptly halted in-person clinical care and research requiring a shift to virtual assessment and treatment. This unexpected transition of a 2-arm randomized controlled trial (RCT) examining interdisciplinary graded exposure treatment (GET Living) compared with multidisciplinary pain management for youth with chronic pain provided an opportunity to implement the first remotely delivered exposure treatment and remotely delivered biomechanical assessment for pediatric chronic pain. Here we describe these new approaches and provide lessons learned to inform future efforts in digital health care., Methods: A total of 68 youth (M=14.2 y; 80.9% female) were enrolled in the RCT (n=31 in-person, n=5 hybrid, n=32 virtual, n=9 withdrew). Of those withdrawn, n=3 withdrew due to COVID-19 related reasons. Some RCT elements required slight modification (eg, e-consent, actigraphy deployment, recruitment, and screening), while others were significantly altered (eg, session format and lab-based biomechanical assessment). Data from exit interviews were also examined to assess perspectives on the virtual format transition., Results: Results showed an increased enrollment rate when virtual care was an option (70.7%) compared with in-person (44.3%). Equivalent rates of completion for daily assessment (in-person, 72.8%; virtual, 73.3) were also observed, and participants described enhanced experience when able to complete exercises and exposures in their home environment during session (vs. a rehabilitation gym) allowing for genuine in vivo exposures (eg, household chores, riding bicycles)., Discussion: Overall, our data demonstrate acceptability, feasibility, and equivalent patient engagement to virtual treatment. Novel methods implemented in this RCT can inform trial design and measures of clinical endpoints for future digital health interventions., Competing Interests: This investigation was supported by NIAMS/R21 AR072921 awarded to L.E.S. This clinical trial is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD. The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Holmes, Mar'i, Simons, Zurakowski, LeBel, O'Brien and Borsook.)

Introduction: Chronic pain affects about 20%-40% of the population and is linked to mental health outcomes and impaired daily functioning. Pharmacological interventions are commonly insufficient for producing relief and recovery of functioning. Behavioural health treatment is key to generate lasting benefits across outcome domains. However, most people with chronic pain cannot easily access evidence-based behavioural interventions. The overall aim of the DAHLIA project is to develop, evaluate and implement a widely accessible digital behavioural health treatment to improve well-being in individuals with chronic pain., Methods and Analysis: The project follows the four phases of the mHealth Agile Development and Evaluation Lifecycle: (1) development and pre-implementation surveillance using focus groups, stakeholder interviews and a business model; (2) iterative optimisation studies applying single case experimental design (SCED) method in 4-6 iterations with n=10 patients and their healthcare professionals per iteration; (3) a two-armed clinical randomised controlled trial enhanced with SCED (n=180 patients per arm) and (4) interview-based post-market surveillance. Data analyses include multilevel modelling, cost-utility and indicative analyses.In October 2021, inter-sectorial partners are engaged and funding is secured for four years. The treatment content is compiled and the first treatment prototype is in preparation. Clinical sites in three Swedish regions are informed and recruitment for phase 1 will start in autumn 2021. To facilitate long-term impact and accessibility, the treatment will be integrated into a Swedish health platform (www.1177.se), which is used on a national level as a hub for advice, information, guidance and e-services for health and healthcare., Ethics and Dissemination: The study plan has been reviewed and approved by Swedish ethical review authorities. Findings will be actively disseminated through peer-reviewed journals, conference presentations, social media and outreach activities for the wider public., Trial Registration Number: NCT05066087., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: There is a need to identify brain connectivity alterations predictive of transdiagnostic processes that may confer vulnerability for affective symptomology. Here, we tested whether amygdala resting-state functional connectivity (rsFC) mediated the relationship between catastrophizing (negative threat appraisals and predicting poorer functioning) and altered threat-safety discrimination learning (critical to flexibly adapt to new and changing environments) in adolescents with persistent pain. We examined amygdala rsFC in 46 youth with chronic pain and 29 healthy peers (age M = 15.8, SD = 2.9; 64 females) and its relationship with catastrophizing and threat-safety learning. We used a developmentally appropriate threat-safety learning paradigm and performed amygdala seed-based rsFC and whole-brain mediation analyses. Patients exhibited enhanced connectivity between the left amygdala and right supramarginal gyrus (SMG) (cluster-level P-FDR < 0.05), whereas right amygdala rsFC showed no group differences. Only in patients, elevated catastrophizing was associated with facilitated threat-safety learning (CS+>CS-; rp = 0.49, P = 0.001). Furthermore, in patients, elevated catastrophizing was associated with reduced left amygdala connectivity with SMG / parietal operculum, and increased left amygdala connectivity with hippocampus, dorsal striatum, paracingulate, and motor regions (P < 0.001). In addition, blunted left amygdala rsFC with right SMG/parietal operculum mediated the association between catastrophizing and threat-safety learning (P < 0.001). To conclude, rsFC between the left amygdala (a core emotion hub) and inferior parietal lobe (involved in appraisal and integration of bodily signals and attentional reorienting) explains associations between daily-life relevant catastrophizing and threat-safety learning. Findings provide a putative model for understanding pathophysiology involved in core psychological processes that cut across diagnoses, including disabling pain, and are relevant for their etiology., (Copyright © 2021 International Association for the Study of Pain.)

Introduction: Functional improvement is a critical outcome for individuals living with chronic pain. Graded exposure treatment (GET) has been associated with statistically significant improvements in functional outcomes for youth with chronic pain by targeting pain-related fear and avoidance., Objective: The aim of the present study was to explore clinically meaningful change in outcomes in adolescents with chronic pain following participation in a GET, and to then classify patients as treatment responders versus nonresponders., Materials and Methods: Participants included 27 youth (Mage=13.5) with chronic pain enrolled in a recently published single-arm randomized baseline trial of GET Living. Reliable change at the individual level was assessed using the Reliable Change Index (RCI). Adolescents were classified as treatment responders if they achieved a reliable change in outcomes across time points and also demonstrated a change in clinical severity range in the expected direction (ie, from severe to moderate)., Results: Reliable and clinically significant improvements in pain-related fear and avoidance, functional disability, and school functioning were demonstrated at discharge, with improvements maintained at 3-month and 6-month follow-up. Among core outcomes, 48% (n=13) of patients were classified as treatment responders in one or more outcomes at discharge, with this increasing to 76% (n=19) at 3-month follow-up., Discussion: Examining reliable and clinically meaningful change (vs. statistical significance alone) provides a way to examine treatment response to an intervention and to enhance the interpretability of findings, helping to bridge the gap between clinical trials and clinical practice by providing guidelines for interpretation., Competing Interests: This investigation was supported by American Pain Society/Sharon S. Keller Chronic Pain Research Grant, Deborah Munroe Noonan Memorial Research Fund, and NIAMS/R21 AR072921 awarded to L.E.S. The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Assessing knowledge and beliefs regarding pain science can identify gaps and misconceptions. The Concept of Pain Inventory (COPI) was recently developed in children with the intent to guide targeted pain science education. We utilized the original COPI item pool to (1) develop a tool to assess an adult's concept of pain in a cohort who had not received pain science education, (2) evaluate its psychometric properties, (3) examine distribution of scores in a cohort of adults who had received pain science education, and (4) examine associations between scores and clinical variables., Materials and Methods: A total cohort of 627 adults were recruited through social media for an online survey. Initial development was conducted on those who had not received prior pain science education (n=125), then the COPI-Adult tool was tested in those who had received prior pain science education (n=502)., Results: The resulting unidimensional 13-item COPI-Adult had acceptable internal consistency (α=0.78) and good test-retest reliability at 1 week (Intraclass Correlation Coefficient3,1=0.84 (95% confidence interval: 0.71-0.91). Higher COPI-Adult scores reflect greater alignment with contemporary pain science. COPI-Adult scores were correlated with revised Neurophysiology of Pain Questionnaire (rNPQ) scores and inversely correlated with average and current pain intensity, and pain interference. Adults who reported having received pain science education had significantly higher mean COPI-Adult scores than those who had not, and this difference exceeded the smallest detectable change., Discussion: The COPI-Adult is a brief questionnaire with promising psychometric properties to identify conceptual gaps or misconceptions to inform individualized pain science education., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Somatic symptoms capture attention, demand interpretation, and promote health behaviors. Symptom appraisal is particularly impactful within uncertain health contexts such as cancer survivorship. Yet, little is known about how individuals make sense of somatic symptoms within uncertain health contexts, nor how this process guides health behaviors., Design: 25 adolescent and young adult survivors of childhood cancer completed semi-structured interviews regarding how they appraise and respond to changing somatic sensations within the uncertain context of survivorship., Main Outcome Measures: Interviews were transcribed verbatim and subjected to a hybrid deductive-inductive thematic analysis, guided by the Cancer Threat Interpretation model., Results: We constructed three themes. S ymptoms as signals of bodily threat (theme 1) captured that participants described commonly interpreting and worrying about everyday sensations as indicating cancer recurrence or new illness. Playing detective with bodily signals (theme 2) captured participants' felt need to employ cognitive and behavioral strategies to determine whether somatic sensations indicated a credible health threat. These two themes are qualified by the final theme, Living with symptom-related uncertainty (theme 3), which captured participants' recognition that post-cancer symptoms are wily and influenced by psychological factors such as anxiety., Conclusions: These data highlight that making sense of everday somatic sensations can be particularly challenging following an experience of cancer. There is a need for novel symptom management approaches that target how somatic sensations are appraised and responded to as signals of bodily threat.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Holmes, Karapanagou, Staffa, Zurakowski, Borra, Simons, Sieberg, Lebel and Borsook.)

Telehealth has emerged as a promising healthcare delivery modality due to its ability to ameliorate traditional access-level barriers to treatment. In response to the onset of the novel coronavirus (COVID-19) pandemic, multidisciplinary pain clinics either rapidly built telehealth infrastructure from the ground up or ramped up existing services. As the use of telehealth increases, it is critical to develop data collection frameworks that guide implementation. This applied review provides a theoretically-based approach to capitalize on existing data sources and collect novel data to inform virtually delivered care in the context of pediatric pain care. Reviewed multisource data are (1) healthcare administrative data; (2) electronic chart review; (3) clinical health registries; and (4) stakeholder feedback. Preliminary telehealth data from an interdisciplinary pediatric chronic pain management clinic (PPMC) serving youth ages 8-17 years are presented to illustrate how relevant implementation outcomes can be extracted from multisource data. Multiple implementation outcomes were assessed, including telehealth adoption rates, patient clinical symptoms, and mixed-method patient-report telehealth satisfaction. This manuscript provides an applied roadmap to leverage existing data sources and incorporate stakeholder feedback to guide the implementation of telehealth in pediatric chronic pain settings through and beyond COVID-19. Strengths and limitations of the modeled data collection approach are discussed within the broader context of implementation science.

In this article we briefly examine the unique features of Single-Case Designs (SCDs) (studies in a single participant), their history and current trends, and real-world clinical applications. The International Collaborative Network for N-of-1 Trials and Single-Case Designs (ICN) is a formal collaborative network for individuals with an interest in SCDs. The ICN was established in 2017 to support the SCD scientific community and provide opportunities for collaboration, a global communication channel, resource sharing and knowledge exchange. In May 2021, there were more than 420 members in 31 countries. A member survey was undertaken in 2019 to identify priorities for the ICN for the following few years. This article outlines the key priorities identified and the ICN's progress to date in these key areas including network activities (developing a communications strategy to increase awareness, collecting/sharing a comprehensive set of resources, guidelines and tips, and incorporating the consumer perspective) and scientific activities (writing position papers and guest editing special journal issues, exploring key stakeholder perspectives about SCDs, and working to streamline ethical approval processes for SCDs). The ICN provides a practical means to engage with this methodology through membership. We encourage clinicians, researchers, industry, and healthcare consumers to learn more about and conduct SCDs, and to join us in our mission of using SCDs to improve health outcomes for individuals and populations., Competing Interests: Authors declare that the article was prepared in the absence of any financial relationships that could be construed as a conflict of interest. Authors JN and SM have a commercial interest in N-of-1 Hub Pty Ltd consultancy company. N-of-1 Hub Pty Ltd has no commercial or financial relationship with the International Collaborative Network for N-of-1 Trials and Single-Case Designs (ICN)., (© 2021 Published by Elsevier Inc.)

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.