Radiation of pain: Psychophysical evidence for a population coding mechanism.

The spread of pain across body locations remains poorly understood but may provide important insights into the encoding of sensory features of noxious stimuli by populations of neurons. In this psychophysical experiment, we hypothesized that more intense noxious stimuli would lead to spread of pain, but more intense light stimuli would not produce perceptual radiation. Fifty healthy volunteers participated in this study wherein four intensities of noxious stimuli (43, 45, 47 and 49°C) were applied to glabrous (hand) and hairy skin (forearm) skin with 5s and 10s durations. Also, four different intensities of visual stimuli displayed on the target bodily area were utilized as a control. Participants provided pain (and light) spatial extent ratings as well as pain (and light) intensity ratings. In the extent rating procedure, participants adjusted the extent of the square displayed on the screen with the extent of pain (or light) which they experienced. Pain extent ratings showed statistically significant radiation of pain indicated by 12.42× greater spatial spread of pain (pain extent) than the area of the stimulation with 49°C (p < 0.001), in contrast to visual ratings which closely approximated the size of the stimulus (1.22×). Pain radiation was more pronounced in hairy than glabrous skin (p < 0.05) and was more pronounced with longer stimulus duration (p < 0.001). Pain intensity explained, on average, only 14% of the pain radiation variability. The relative independence of the pain radiation from perceived pain intensity indicates that distinct components of population coding mechanisms may be involved in the spatial representation of pain versus intensity coding.

A narrative review of the literature on illness uncertainty in hypermobile ehlers-danlos syndrome: implications for research and clinical practice.

BACKGROUND: Hypermobile Ehlers-Danlos syndrome (hEDS) is characterized by joint and skin laxity, and often accompanied by chronic pain, dysautonomia, increased distress and, functional limitations. The journey to accurate diagnosis is often prolonged due to unclear etiology of symptoms. This manuscript is a narrative review of the literature on illness uncertainty (IU) in hEDS, highlighting the unique facets of IU in this population, as compared to the broader chronic pain population (given symptom overlap between these two disease groups), that warrant additional investigation. Additionally, we considered the unique challenges associated with IU in the context of the developmental nuances of pediatric populations. Specifically, we aimed to (1) map the extant literature of the IU experience in chronic pain conditions broadly including the pediatric and adult research to identify key concepts related to IU and incorporate potential developmental considerations in IU; (2) delineate and describe the IU experience specifically in patients with hEDS, with the goal of identifying gaps in the literature based on aspects of presentation in hEDS that do and do not differ from the broader chronic pain population; and (3) elucidate the potential areas of adverse impact of IU in both general chronic pain populations, and those with hEDS specifically, to provide actionable areas for future research and clinical care of individuals with hEDS. Results of this review indicate that IU has been well-studied in chronic pain generally, but inadequately evaluated in hEDS specifically. Specific features of hEDS (complexity of the disorder, involvement of multiple bodily systems, contribution of organic pathology) may uniquely contribute to IU in this population. This review suggests that ambiguities surrounding the diagnosis of hEDS, symptom course, and treatment recommendations, along with misdiagnosis, perceived dismissal of symptoms, or attribution of symptoms to mental health concerns might increase risk for IU and related distress in patients. CONCLUSION: Findings from the present review suggest that distinct features of hEDS yield a set of driving factors for IU that may be somewhat different than those faced by patients with chronic pain or other medical conditions. The development of a validated measure of IU to appropriately assess this construct in patients with hEDS is a research priority. In the clinical setting, providers should be attentive to the potentially aversive diagnostic and treatment experiences reported by patients and attempt to provide clear explanations based on the extant knowledge of hEDS, and implement best-practice recommendations for multidisciplinary treatment.

Development and evaluation of the patient-reported outcomes measurement information system (PROMIS) pediatric pain quality item bank and short form.

ABSTRACT: Pain is a common problem among children, particularly those with pediatric chronic diseases. Multifaceted assessment of pain can improve communication about pain and help clinicians characterize, differentiate, and treat a patient's unique experience of pain. Pain quality is an important domain of pain, describing the subjective sensory experiences associated with pain as well as the affective experiences of pain. The aim of the current study was to quantitatively evaluate the measurement properties of the 59 Patient-Reported Outcomes Measurement Information System pediatric pain quality candidate items developed as part of the National Institutes of Health's Patient-Reported Outcomes Measurement Information System initiative with input from children and adolescents with chronic pain. Participants included N = 448 pediatric patients between 8 and 18 years of age with chronic health conditions with a prominent component of chronic or recurrent pain, including juvenile fibromyalgia, juvenile idiopathic arthritis, and sickle cell disease. A confirmatory factor analysis revealed a unidimensional model fit the data best, with 56 of the 59 items demonstrating good psychometric properties for inclusion in the final measure. In addition, a consensus-building method was used to establish 2 versions of a short form measure-one with 8 items focused primarily on the sensory pain qualities and one with 8 items focused on affective pain qualities. The final measure shows good reliability and validity, and is recommended for use in research and clinical care with pediatric populations.

Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain.

INTRODUCTION: Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline. This will facilitate risk stratification in adolescent patients with chronic MSK pain and more resourceful allocation of patients to costly and potentially burdensome multidisciplinary pain treatment approaches. METHODS AND ANALYSIS: Here we describe a multi-institutional effort to collect, curate and analyse a high dimensional data set including epidemiological, psychometric, quantitative sensory, brain imaging and biological information collected over the course of 12 months. The aim of this effort is to derive a multivariate model with strong prognostic power regarding the clinical course of adolescent MSK pain and function. ETHICS AND DISSEMINATION: The study complies with the National Institutes of Health policy on the use of a single internal review board (sIRB) for multisite research, with Cincinnati Children's Hospital Medical Center Review Board as the reviewing IRB. Stanford's IRB is a relying IRB within the sIRB. As foreign institutions, the University of Toronto and The Hospital for Sick Children (SickKids) are overseen by their respective ethics boards. All participants provide signed informed consent. We are committed to open-access publication, so that patients, clinicians and scientists have access to the study data and the signature(s) derived. After findings are published, we will upload a limited data set for sharing with other investigators on applicable repositories. TRIAL REGISTRATION NUMBER: NCT04285112.

Healthcare utilization among youth with Ehlers-Danlos syndrome hypermobile type.

Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited disorders of connective tissue. EDS hypermobility type (EDS-HT), characterized by joint hypermobility, is most common and increasingly recognized in pediatrics. Treatment involves protecting joints, preventing injuries, and managing symptoms/comorbidities. Pediatric EDS-HT patients often see multiple medical providers; however, data on healthcare utilization (HCU) in this population are lacking. This retrospective, electronic chart review examines HCU data 1 year prior and subsequent to a new diagnosis of EDS-HT using Villefranche criteria. Demographics, diagnoses, and HCU (office visits, therapies, hospital encounters/procedures, and tests) were obtained for N = 102 youth attending a Connective Tissue Disorder Clinic over a 21-month timeframe. After EDS-HT diagnosis, HCU patterns shifted to reflect greater involvement of therapy (physical, psychological, and occupational) and symptom management. More genetics, rheumatology, and orthopedics visits occurred prediagnosis, and more physical therapy, pain management, cardiology, and neurology visits occurred postdiagnosis. Testing and hospital encounter/procedure frequencies did not change. Overall, the pattern of HCU changed from diagnostic to treatment, in accordance with evidence-based EDS-HT care. Understanding HCU patterns of pediatric patients with EDS-HT can elucidate patient interaction with the health care system, with the potential to inform and improve the standard of care.

Medical Management of Chronic Pancreatitis in Children: A Position Paper by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee.

ABSTRACT: This position paper summarizes the current understanding of the medical management of chronic pancreatitis (CP) in children in light of the existing medical literature, incorporating recent advances in understanding of nutrition, pain, lifestyle considerations, and sequelae of CP. This article complements and is intended to integrate with parallel position papers on endoscopic and surgical aspects of CP in children. Concepts and controversies related to pancreatic enzyme replacement therapy (PERT), the use of antioxidants and other CP medical therapies are also reviewed. Highlights include inclusion of tools for medical decision-making for PERT, CP-related diabetes, and multimodal pain management (including an analgesia ladder). Gaps in our understanding of CP in children and avenues for further investigations are also reviewed.

Development and Psychometric Evaluation of the PROMIS Pediatric Pain Intensity Measure in Children and Adolescents with Chronic Pain.

The goal of the current study was to enhance the measurement of the pediatric chronic pain experience through a methodologically rigorous approach. This paper outlines the development and initial validation of a pain intensity measure for pediatric patients with chronic pain using Patient-Reported Outcomes Measurement Information System methodology. Measure development incorporated feedback from children with painful conditions. Based on input from pediatric participants and content experts, 4 candidate items assessing pain intensity were included for large scale testing. Children completed self-report items pertaining to their pain experience that were developed as part of a larger pool of new candidate Patient-Reported Outcomes Measurement Information System pediatric pain domain items as well as measures of pain interference, depressive symptoms, fatigue, pain behavior, pain intensity, and pain catastrophizing. The final sample for the large scale testing included N = 442 pediatric patients between the ages 8 to 18 years (Mean age = 13.54, Standard Deviation = 2.78; 71.27% female) experiencing chronic pain. Psychometric analysis resulted in a final measure that included 3 items with evidence of reliability (Cronbach alpha = .82) and convergent validity. The Likert format of the response options may be preferable to the traditional numeric rating scale for use in pediatric populations who experience chronic pain based on patients' feedback, which was directly utilized in designing the scale. Further, the inclusion of fewer and clinically meaningful response options should reduce ambiguity for young respondents. PERSPECTIVE: We have developed and evaluated a clinically sensitive and psychometrically precise 3-item pain intensity measure with Likert-type responses for self-report use among children and adolescents ages 8 to 18 years with chronic pain. Development of the item content and response options included input from children and adolescents with chronic pain. The development of pain intensity items with pediatric appropriate language, and labeled, fewer response options to yield maximal clinically meaningful information improves the precision of pain intensity measurement in children.

The Role of Neuraxial Opioids in Pediatric Practice.

Neuraxial-spinal and epidural-administration of opioids can be an effective method for controlling pain for children in a number of clinical settings. Understanding the basic pharmacologic and logistical concepts will make it easier for pediatricians to advocate for their patients, and support patients and families when circumstances suggest that neuraxial opioid treatment is appropriate. This review article summarizes the basic concepts of pharmacology, drug choice, side effects, and complications as well as situations in which neuraxial opioids are appropriate in children.

In-hospital and 90-day outcomes after total pancreatectomy with islet autotransplantation for pediatric chronic and acute recurrent pancreatitis.

Total pancreatectomy with islet autotransplantation (TPIAT) is used to treat debilitating chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) that has failed medical and endoscopic therapy. We performed a retrospective review of TPIAT patients at a free-standing children's hospital to evaluate perioperative outcomes. Twenty patients (median age 13, 65% female) underwent TPIAT (2015 through 2017). Of the 20 patients, 95% had CP and 1 patient (5%) had ARP alone. Seventy-five percent of the patients had a pancreatitis-associated genetic mutation; 40% had pancreas divisum. The median surgical time was 757 (IQR 657 to 835) minutes. Median islet equivalents per kg of body weight (IEQ/kg) were 6404 (IQR 5018 to 7554). At 90 days postoperatively vs preoperatively, significantly fewer patients were receiving parenteral nutrition (0% vs 25%, P = .006) and opioids (45% vs 75%, P = .01). Short Form 36-Item Health Survey (SF-36) physical health module scores and total scores improved (34.0 preoperatively vs 54.6 at 90 days, P = .008, and 47.1 vs 65.3, P = .007, respectively); SF-10 physical health scores also improved (13.4 vs 33.1, P = .02). Insulin requirement decreased from 0.5 unit/kg/day to 0.4 unit/kg/day between discharge and 90 days (P = .02). TPIAT is an effective option when debilitating disease persists despite maximal medical and endoscopic therapy. Opioid, parenteral nutrition, and exogenous insulin use can successfully be weaned within 90 days after TPIAT, with gains in health-related quality of life.

Development and validation of the self-reported PROMIS pediatric pain behavior item bank and short form scale.

Pain behaviors are important indicators of functioning in chronic pain; however, no self-reported pain behavior instrument has been developed for pediatric populations. The purpose of this study was to create a brief pediatric measure of patient-reported pain behaviors as part of the Patient-Reported Outcome Measurement Information System (PROMIS). A pool of 47 candidate items for this measure had been previously developed through qualitative research. In this study, youth with chronic pain associated with juvenile fibromyalgia, juvenile idiopathic arthritis, or sickle cell disease (ages 8-18 years) from 3 pediatric centers completed all 47 candidate items for development of the pain behavior item bank along with established measures of pain interference, depressive symptoms, fatigue, average pain intensity, and pain catastrophizing. Caregivers reported on sociodemographic information and health history. Psychometric properties of the pain behavior items were examined using an item response theory framework with confirmatory factor analysis and examination of differential item functioning, internal consistency, and test information curves. Results were used along with expert consensus and alignment with the adult PROMIS pain behavior items to arrive at an 8-item pediatric pain behavior short form, and all 47 items were retained in a calibrated item bank. Confirmatory factor analysis and correlations with validated measures of pain, pain interference, and psychosocial functioning provided support for the short form's reliability and validity. The new PROMIS pediatric pain behavior scale provides a reliable, precise, and valid measure for future research on pain behavior in school-aged children with chronic pain.

Anxiety Adversely Impacts Response to Cognitive Behavioral Therapy in Children with Chronic Pain.

OBJECTIVE: To evaluate whether clinical anxiety in children presenting to a pediatric pain management center is associated with a poorer treatment response for those who completed pain-focused cognitive behavioral therapy (CBT). STUDY DESIGN: The total sample consisted of 175 children, 40 of whom completed CBT for chronic pain. The Screen for Child Anxiety Related Emotional Disorders was completed at initial evaluation and outcome measures (average pain intensity and the Functional Disability Inventory) were collected during the initial evaluation and at the end of CBT. Group differences in outcomes were examined following CBT. The role of anxiety in CBT initiation and completion was also explored. RESULTS: Presence of clinical anxiety was associated with greater initiation and/or completion of pain-focused CBT but also a poorer treatment response. Specifically, the group with subclinical anxiety exhibited a substantial reduction in pain intensity, and the group with clinical anxiety exhibited a more limited response to treatment (F [1, 36] = 13.68 P < .01). A similar effect was observed for Functional Disability Inventory, such that the group with clinical anxiety had a significantly smaller response to treatment (F [1, 38] = 4.33 P < .05). The difference in pain and disability between groups following CBT suggest moderate effects (Cohen d = 0.77 and 0.78, respectively). CONCLUSIONS: Although youths with clinical anxiety are more likely to start and/or complete pain-focused CBT, anxiety has an adverse impact on CBT treatment response in children with chronic pain. Identification of patients with anxiety and use of tailored behavioral interventions may improve clinical outcomes.

Longitudinal evaluation of patient-reported outcomes measurement information systems measures in pediatric chronic pain.

The Patient-Reported Outcomes Measurement Information System (PROMIS) initiative is a comprehensive strategy by the National Institutes of Health to support the development and validation of precise instruments to assess self-reported health domains across healthy and disease-specific populations. Much progress has been made in instrument development, but there remains a gap in the validation of PROMIS measures for pediatric chronic pain. The purpose of this study was to investigate the construct validity and responsiveness to change of 7 PROMIS domains for the assessment of children (ages: 8-18) with chronic pain--Pain Interference, Fatigue, Anxiety, Depression, Mobility, Upper Extremity Function, and Peer Relationships. The PROMIS measures were administered at the initial visit and 2 follow-up visits at an outpatient chronic pain clinic (CPC; N = 82) and at an intensive amplified musculoskeletal pain day-treatment program (N = 63). Aim 1 examined construct validity of PROMIS measures by comparing them with corresponding "legacy" measures administered as part of usual care in the CPC sample. Aim 2 examined sensitivity to change in both CPC and amplified musculoskeletal pain samples. Longitudinal growth models showed that PROMIS' Pain Interference, Anxiety, Depression, Mobility, Upper Extremity, and Peer Relationship measures and legacy instruments generally performed similarly with slightly steeper slopes of improvement in legacy measures. All 7 PROMIS domains showed responsiveness to change. Results offered initial support for the validity of PROMIS measures in pediatric chronic pain. Further validation with larger and more diverse pediatric pain samples and additional legacy measures would broaden the scope of use of PROMIS in clinical research.

The catheter hub disinfection cap as esophageal foreign body.

Disinfection caps are increasingly being used to prevent catheter-associated bloodstream infections. These devices, designed for continuous passive disinfection of catheter hubs, are typically small and often brightly colored. As such, they have the potential to become pediatric airway and esophageal foreign bodies. We report two patients who developed esophageal foreign body following ingestion of disinfection caps. Given the increasing use of these devices, it is imperative that health care providers be aware of this potential iatrogenic problem. We propose that the use of disinfection caps may not be appropriate in pediatric patients with risk factors for foreign body ingestion.

Pharmacological treatment of chronic non-cancer pain in pediatric patients.

Chronic pain in children and young adults occurs frequently and contributes to early disability as well as personal and familial distress. A biopsychosocial approach to evaluation and treatment is recommended. Within this approach, there is a role for pharmacologic intervention. A variety of medications are used for chronic pain conditions in pediatric patients. Medication classes include anticonvulsants, muscle relaxants, antidepressants, opioids, local anesthetics, and anti-inflammatory drugs. Data is sparse, and most medications are used without condition-specific approval by national regulatory agencies such as the Food and Drug Administration in the US and the European Medicines Agency. In the absence of evidence on which to base practice, optimal drug therapy decisions rest on understanding proposed mechanisms of pain conditions, extrapolation from adult data-when such exists, and empirical and experiential knowledge. Drug delivery systems have evolved, and practitioners have to decide amongst not only medication classes, but also routes of delivery. Opioids are not recommended for use by non-pain specialists for the treatment of pediatric chronic pain, and even then the issues are more complex than can be addressed here. This article reviews the major medications used for pediatric chronic pain conditions.

Differential changes in functional disability and pain intensity over the course of psychological treatment for children with chronic pain.

Patients presenting for treatment of chronic pain often believe that pain reduction must be achieved before returning to normal functioning. However, treatment programs for chronic pain typically take a rehabilitative approach, emphasizing decreasing pain-related disability first with the expectation that pain reduction will follow. This information is routinely provided to patients, yet no studies have systematically examined the actual trajectories of pain and disability in a clinical care setting. In this study of youth with chronic pain (N=94, 8 to 18 years), it was hypothesized that 1) functional disability and pain would decrease over the course of psychological treatment for chronic pain and 2) functional disability would decrease more quickly than pain intensity. Participants received cognitive behavioral therapy (CBT) for pain management (M=5.6 sessions) plus standard medical care. The Functional Disability Inventory and a Numeric Rating Scale of average pain intensity were completed by the child at every CBT session. Hierarchical linear modeling was conducted to examine the longitudinal trajectories of disability and pain. Standardized estimates of the slopes of change were obtained to test differences in rates of change between pain and disability. Results showed an overall significant decline in functional disability over time. Although pain scores reduced slightly from pretreatment to posttreatment, the longitudinal decline over treatment was not statistically significant. As expected, the rate of change of disability was significantly more rapid than pain. Evidence for variability in treatment response was noted, suggesting the need for additional research into individual trajectories of change in pediatric pain treatment.

Pain care for patients with epidermolysis bullosa: best care practice guidelines.

BACKGROUND: Inherited epidermolysis bullosa (EB) comprises a group of rare disorders that have multi-system effects and patients present with a number of both acute and chronic pain care needs. Effects on quality of life are substantial. Pain and itching are burdensome daily problems. Experience with, and knowledge of, the best pain and itch care for these patients is minimal. Evidence-based best care practice guidelines are needed to establish a base of knowledge and practice for practitioners of many disciplines to improve the quality of life for both adult and pediatric patients with EB. METHODS: The process was begun at the request of Dystrophic Epidermolysis Bullosa Research Association International (DEBRA International), an organization dedicated to improvement of care, research and dissemination of knowledge for EB patients worldwide. An international panel of experts in pain and palliative care who have extensive experience caring for patients with EB was assembled. Literature was reviewed and systematically evaluated. For areas of care without direct evidence, clinically relevant literature was assessed, and rounds of consensus building were conducted. The process involved a face-to-face consensus meeting that involved a family representative and methodologist, as well as the panel of clinical experts. During development, EB family input was obtained and the document was reviewed by a wide variety of experts representing several disciplines related to the care of patients with EB. RESULTS: The first evidence-based care guidelines for the care of pain in EB were produced. The guidelines are clinically relevant for care of patients of all subtypes and ages, and apply to practitioners of all disciplines involved in the care of patients with EB. When the evidence suggests that the diagnosis or treatment of painful conditions differs between adults and children, it will be so noted. CONCLUSIONS: Evidence-based care guidelines are a means of standardizing optimal care for EB patients, whose disease is often times horrific in its effects on quality of life, and whose care is resource-intensive and difficult. The guideline development process also highlighted areas for research in order to improve further the evidence base for future care.

The interplay of parent and adolescent catastrophizing and its impact on adolescents' pain, functioning, and pain behavior.

OBJECTIVES: Catastrophizing is a coping style linked to poorer patient outcomes. Little attention has focused on the parent-adolescent dyad and catastrophizing as a shared coping style. The purpose of this study was to: (1) examine the effects of adolescent and parent pain catastrophizing on adolescent functioning and (2) explore concordance in catastrophizing in parent-adolescent dyads, with equal interest in outcomes of dyads with discordant coping styles. METHODS: Pain intensity, catastrophizing, depressive symptoms, quality of life, and pain behaviors were assessed in adolescents (ages 11 to 17) presenting to a pediatric chronic pain clinic (N=240). RESULTS: Significant correlations between (1) parent and adolescent catastrophizing; (2) catastrophizing and pain behaviors; and (3) catastrophizing and adolescent outcomes were found. Parents and adolescents were classified into concordant or discordant dyads based on catastrophizing with a majority of dyads (>70%) showing concordant coping styles. Among discordant dyads, functional disability and depressive symptoms were significantly higher in a dyad with a high catastrophizing adolescent and low catastrophizing parent. DISCUSSION: Results provide further support for catastrophizing being a maladaptive coping strategy for adolescents with pain and their parents. Greater adolescent catastrophizing was related to increased pain behaviors and poorer adolescent functioning. Parent catastrophizing also seems related to poorer adolescent outcomes, and most parent-adolescent dyads showed concordance in use of catastrophizing, which may suggest a shared tendency for adaptive or maladaptive styles of coping with pain. Future research should investigate pain coping at a dyadic or family level to explore how family coping styles magnify distress and disability or buffer adolescents from such problems.

Complex regional pain syndrome in children: asking the right questions.

BACKGROUND: Complex regional pain syndrome (CRPS) is a painful disorder without a known unifying mechanism. There are little data on which to base evaluation and treatment decisions, and what data are available come from studies involving adults; however, even that literature is relatively sparse. Developing robust research for CRPS in children is essential for the progress toward optimal treatment. OBJECTIVES: To determine potential avenues of research in pediatric CRPS based on a review of the literature. Areas of concern include diagnostic criteria, peripheral mechanisms, central nervous system mechanisms, the role of the autonomic nervous system, possible risk factors, options for prevention and potential avenues of treatment. METHODS: A literature review was performed and the results applied to form the hypotheses posited in the form of research questions. RESULTS AND CONCLUSIONS: CRPS is a complicated entity that is more than a painful sensory condition. There is evidence for peripheral inflammatory and neurological changes, and reorganization in both sensory and motor cortexes. In addition, a significant motor component is frequently observed and there appear to be tangible risk factors. Many of these pieces of evidence suggest options for prevention, treatment and monitoring progress and outcome. Most of the data are derived from adult studies and need to be replicated in children. Furthermore, there may be factors unique to pediatrics due to developmental changes in neuroplasticity as well as somatic, endocrinological and emotional growth. Some of these developmental factors may shed light on the adult condition.