Recommendations for Patient-Reported Outcomes Measurement Information System pediatric measures in youth with chronic pain: a COnsensus-based Standards for the selection of health Measurement INstruments systematic review of measurement properties.

ABSTRACT: The Patient-Reported Outcome Measurement Information System (PROMIS) pediatric measures assess physical, emotional, and social health among children and adolescents. However, their measurement properties have not been systematically examined in youth with chronic pain. A systematic review applying the COnsensus based Standards for the selection of health Measurement INstruments (COSMIN) methodology was conducted to evaluate self-reported PROMIS pediatric measures in youth with chronic pain, assessing 8 measurement properties across all versions (item bank, short form, and computer adaptive testing) from 63 studies covering 25 measures. Moderate or high-quality evidence was most available for content validity, structural validity, internal consistency (measurement precision), and construct validity. Four short-form PROMIS pediatric measures-mobility, anxiety, depressive symptoms, and physical stress experiences-achieved recommendation for the use in chronic pain clinical trials; 7 approached recommendation and 14, including the commonly used PROMIS Pediatric Pain Interference Scale, would be recommended with further evidence. Recommendations were also provided for the use of each measure in observational studies. Overall, based on the existing evidence, a total of 11 self-reported PROMIS pediatric short-form measures, including pain intensity, pain behavior, mobility, sleep disturbance, sleep-related impairment, anxiety, depressive symptoms, psychological stress experiences, physical stress experiences, family relationships, and positive effect, are recommended or approaching recommendation for use in youth ages 8 to 19 years with chronic pain. Research is needed to further establish test-retest reliability, measurement errors, cross-cultural validity, and responsiveness. Future work should expand the evaluation of PROMIS pediatric measures in subpopulations of youth with chronic pain, particularly young children and those with neurodevelopmental disabilities.

The Influence of Children's Pain-Related Attention Shifting Ability and Pain Catastrophizing Upon Negatively Biased Pain Memories in Healthy School Children.

The current study investigated the influence of children's ability to flexibly shift attention toward and away from pain information on the development of negatively biased pain memories, thereby employing a direct measure of attention control reliant on behavioral responses in the context of pain (ie, an attention switching task). The direct influence of children's attention-shifting ability and pain catastrophizing as well as the moderating role of this shifting ability in the relationship between pain catastrophizing and the development of negatively biased pain memories was examined. Healthy school children (N = 41; 9-15 years old) received painful heat stimuli and completed measures of state and trait pain catastrophizing. They then performed an attention-switching task wherein they had to shift attention between personally relevant pain-related and neutral cues. Two weeks after the painful task, children's pain-related memories were elicited via telephone. Findings indicated that children's reduced ability to disengage attention away from pain information predicted more fear memory bias 2 weeks later. Children's pain-related attention-shifting ability did not moderate the relationship between children's pain catastrophizing and negatively biased pain memories. Findings highlight the contribution of children's attention control skills in the development of negatively biased pain memories. PERSPECTIVE: Results of the current study indicate that children with a reduced ability to shift attention away from pain information are at risk for developing negatively biased pain memories. Findings can inform interventions to minimize the development of these maladaptive negatively biased pain memories by targeting pain-relevant attention control skills in children.

The Role of Serotonergic and Noradrenergic Descending Pathways on Performance-Based Cognitive Functioning at Rest and in Response to Exercise in People with Chronic Whiplash-Associated Disorders: A Randomized Controlled Crossover Study.

(1) Background: Dysregulation in serotonergic and noradrenergic systems may be implicated in the neurobiophysiological mechanisms underlying pain-related cognitive impairment in chronic whiplash-associated disorders (CWAD). This study aimed to unravel the role of serotonergic and noradrenergic descending pathways in cognitive functioning at rest and in response to exercise in people with CWAD. (2) Methods: 25 people with CWAD were included in this double-blind, randomized, controlled crossover study. Endogenous descending serotonergic and noradrenergic inhibitory mechanisms were modulated by using a single dose of a selective serotonin reuptake inhibitor (Citalopram) or a selective norepinephrine reuptake inhibitor (Atomoxetine). Cognitive performance was studied at rest and in response to exercise (1) without medication intake; (2) after intake of Citalopram; and (3) after intake of Atomoxetine. (3) Results: After Atomoxetine intake, selective attention improved compared with the no medication day (p < 0.05). In contrast, a single dose of Citalopram had no significant effect on cognitive functioning at rest. When performing pairwise comparisons, improvements in selective attention were found after exercise for the no medication condition (p < 0.05). In contrast, after intake of Citalopram or Atomoxetine, selective and sustained attention worsened after exercise. (4) Conclusions: A single dose of Atomoxetine improved selective attention only in one Stroop condition, and a single dose of Citalopram had no effect on cognitive functioning at rest in people with CWAD. Only without medication intake did selective attention improve in response to exercise, whereas both centrally acting medications worsened cognitive performance in response to a submaximal aerobic exercise bout in people with CWAD.

Towards precision pain medicine for pain after cancer: the Cancer Pain Phenotyping Network multidisciplinary international guidelines for pain phenotyping using nociplastic pain criteria.

Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice.

Spreading the word: pediatric pain education from treatment to prevention.

Pain affects everyone hence one can argue that it is in each individual's interest to understand pain in order to hold correct and adaptive beliefs and attitudes about pain. In addition, chronic pain is reaching pandemic proportions and it is now well known that people living with chronic pain have a reduced life expectancy. To address and to prevent the growth of this public health disaster, we must start looking beyond adulthood. How children view pain has an impact on their behavioral coping responses which in turn predict persistent pain early in the lifespan. In addition, children who suffer from chronic pain and who are not (properly) treated for it before adolescence have an increased risk of having chronic pain during their adult life. Explaining pain to children and youth may have a tremendous impact not only on the individual child suffering from chronic pain but also on society, since the key to stop the pain pandemic may well lie in the first two decades of life. In order to facilitate the acquisition of adaptive behavioral coping responses, pain education aims to shift people's view on pain from being an apparent threat towards being a compelling perceptual experience generated by the brain that will only arise whenever the conceivable proof of danger to the body is greater than the conceivable proof of safety to the body. Nowadays a lot of pain education material is available for adults, but it is not adapted to children's developmental stage and therefore little or not suitable for them. An overview of the state-of-the-art pain education material for children and youth is provided here, along with its current and future areas of application as well as challenges to its development and delivery. Research on pediatric pain education is still in its infancy and many questions remain to be answered within this emerging field of investigation.

The Effect of Robot-Led Distraction during Needle Procedures on Pain-Related Memory Bias in Children with Chronic Diseases: A Pilot and Feasibility Study.

The current study evaluated the feasibility and preliminary clinical impact of robot-led distraction during needle procedures in children with chronic diseases on pain-related memories. Participants were 22 children (8−12 years old) diagnosed with a chronic disease (e.g., chronic immune deficiency) and undergoing a needle procedure as part of their routine treatment. Children were randomized to the experimental group (i.e., robot-led distraction) or control group (i.e., usual care). For feasibility, we evaluated study- and needle-procedure-related characteristics, intervention fidelity and acceptability, and nurse perceptions of the intervention. Primary clinical outcomes included children's memory bias for pain intensity and pain-related fear (1 week later). Results indicated that intervention components were >90% successful. Overall, the robot-led distraction intervention was perceived highly acceptable by the children, while nurse perceptions were mixed, indicating several challenges regarding the intervention. Preliminary between-group analyses indicated a medium effect size on memory bias for pain intensity (Hedges' g = 0.70), but only a very small effect size on memory bias for pain-related fear (Hedges' g = 0.09), in favor of the robot-led distraction intervention. To summarize, while feasible, certain challenges remain to clinically implement robot-led distraction during needle procedures. Further development of the intervention while accounting for individual child preferences is recommended.

The relation between children's attention bias to pain and children's pain-related memory biases is moderated by parental narrative style.

Children's heightened attention to pain and parental narrative style have been linked to the development of negatively-biased pain memories in children (i.e., recalling higher levels of pain and fear than initially reported, which robustly predicts maladaptive pain outcomes). However, the interplay between child attention bias and parental narrative style remains to be assessed. This study aims to fill this gap using enhanced paradigms assessing children's cognitive biases for cues signaling actual pain. Healthy school children (N = 63; 9-15 years old) received painful heat stimuli while performing a spatial cueing task measuring attention bias to cues signaling actual pain. Parent-child interaction upon completion of the painful task, was coded for parental narrative style (i.e., elaboration, repetition and evaluation). Children's pain-related memories were elicited two weeks later. Findings indicated that children showed an attention bias to cues signaling pain. Furthermore, children who were hypervigilant to pain cues benefitted from parents elaborating more about the pain experience, while children who avoided pain cues developed more negatively-biased pain memories if parents had a more elaborative style compared to a more evaluative parental style. In conclusion, this study suggests that optimal ways to talk about children's pain depend upon child characteristics (i.e., children's attention bias to pain).

The Effect of a Pain Educational Video Upon Child Pain-Related Memory and the Moderating Role of Parental Pain- and Non-Pain-Attending Verbalizations: An Experimental Lab-Based Study.

OBJECTIVES: Early memories of pain contribute to fear and may underlie the maintenance and development of chronic pain into adulthood. Accordingly, understanding determinants that may impact children's pain memory development is key. This study examined (a) the effect of a brief engaging pain educational video in healthy children before undergoing an experimental pain task upon children's recalled pain intensity and pain-related fear and (b) the moderating role of parental pain- and non-pain-attending verbalizations before and after the pain task. METHODS: Seventy-seven children (8-15 years old) participated in an experimental heat pain task, including actual heat pain stimuli delivered through a thermode on their forearm. Children were randomized to the experimental group (i.e., watching a pain educational video) or the control group (i.e., no video). Children's recalled pain intensity and pain-related fear were elicited 2 weeks later. RESULTS: Findings showed that recalled pain intensity (but not recalled pain-related fear) of children who watched the pain educational video was significantly lower compared to the control group (p = .028). Further, parental pain-attending verbalizations before the pain task moderated the impact of the video upon children's recalled pain intensity (p = .038). Specifically, children in the control group, but not the experimental group, whose parents used less pain-attending verbalizations recalled higher pain intensity, whereas children whose parents used more pain-attending verbalizations recalled lower pain intensity. CONCLUSIONS: As children's pain memories have important implications for pain assessment, treatment, and health across the lifespan, these findings might have important implications for the prevention of development or maintenance of maladaptive pain-related outcomes.

Pain science education for children living with and beyond cancer: Challenges and research agenda.

Pain in children living with and beyond cancer is understudied and undertreated. Pain science education (PSE) is a conceptual change strategy facilitating patients' understanding of the biopsychosocial aspects of pain. Preliminary studies on the adaptation of PSE interventions to adults with and beyond cancer provide a foundation for pediatric research. PSE could help childhood cancer survivors experiencing persistent pain and pain-related worry after active treatment. PSE may also help children receiving cancer treatment, providing them with a foundation of adaptive pain beliefs and cognitions, and preparing them for procedural and treatment-related pain. We direct this paper toward pediatric oncology clinicians, policy makers, and researchers working with children living with and beyond cancer. We aim to (a) identify challenges in adapting PSE for children living with and beyond cancer, (b) offer possible solutions, and (c) propose research questions to guide the implementation of PSE for children living with and beyond cancer.

The Impact of Parental Presence on Their Children During Painful Medical Procedures: A Systematic Review.

OBJECTIVE: Whether parental presence during their children's painful medical procedures is advantageous with regard to children's pain-related outcomes is questionable. Research on this topic is equivocal, and additional questions, such as whether levels of parental involvement may play a role as well, remain to be addressed. The purpose of this systematic review is to summarize and critically appraise the literature on the impact of parental presence vs absence during their children's painful medical procedures on the child's pain-related outcomes. METHODS: The review protocol was registered on Prospero (ID CRD42018116614). A systematic search in PubMed, Web of Science, and PsycArticles resulted in 22 eligible studies incorporating 2,157 participants. Studies were considered eligible if they included children (≤18 years old) undergoing a painful medical procedure and compared parental presence and/or involvement with parental absence during the procedure. RESULTS: The children's pain-related outcomes included self-reported pain intensity, self-reported fear, anxiety and distress, observed pain-related behavior, and physiological parameters. Overall, evidence points in the direction of beneficial effects of parental presence vs absence with regard to children's self-reported pain intensity and physiological parameters, whereas mixed findings were recorded for children's self-reported fears, anxiety and distress, and observed pain-related behaviors. CONCLUSIONS: To provide clear recommendations on how to involve the parent during the procedure, as well as for which type of children and parents parental presence has the best effects, further research is needed, as indicated in this review.

Do Parental Pain Knowledge, Catastrophizing, and Hypervigilance Improve Following Pain Neuroscience Education in Healthy Children?

Pediatric chronic pain is a challenging problem for children and their families, although it is still under-recognized and under-treated. The aim of this study was to investigate whether a pain neuroscience education program for children (PNE4Kids) delivered to healthy children aged 8 to 12 years old and attended by their parents would result in improved parental knowledge about pain neurophysiology, decreased parental pain catastrophizing about their own pain and their children's, decreased parental pain vigilance and awareness, and decreased fear of pain in children. Twenty-seven healthy child-parent dyads received a 45 min PNE4Kids session. Demographic data were collected, and the Neurophysiology of Pain Questionnaire (NPQ), Fear of Pain Questionnaire-Parent Proxy Report (FOPQ-P), Pain Catastrophizing Scale (PCS), Pain Catastrophizing Scale for Parents (PCS-P), and the Pain Vigilance and Awareness Questionnaire (PVAQ) were completed by the parents before and after the PNE4Kids session. Twenty-six dyads completed study participation. In response to the PNE4Kids session, significant short-term (1 week) improvements were shown in the NPQ (p < 0.001) and the FOPQ-P (p = 0.002). Parents' level of pain knowledge and children's fear of pain, reported by their parents, improved after a 45 min PNE4Kids session. Thus, PNE4Kids should likewise be further investigated in healthy child-parent dyads as it might be useful to target parental and children's pain cognitions at a young age.

The effect of a pain educational video intervention upon child pain-related outcomes: A randomized controlled study.

BACKGROUND: Pain neuroscience education (PNE) has received increasing research attention demonstrating beneficial effects on pain-related outcomes in adults. Conversely, studies on the effectiveness of PNE in children are scarce. METHODS: This study investigated the effect of a pain educational video intervention on child pain-related outcomes (i.e. experienced pain intensity, pain-related fear and catastrophic worry about pain, pain threshold and pain knowledge) in healthy children undergoing an experimental pain task. Furthermore, the moderating role of children's demographic (i.e. sex and age) and psychological (i.e. baseline pain knowledge and anticipated pain intensity, pain-related fear and catastrophic worry) characteristics was examined. Participants were 89 children (Mage  = 11.85, SD = 1.78), randomly assigned to either a condition whereby they were instructed to watch a brief pain educational video (i.e. experimental group) or to a control condition whereby they did not watch any video. RESULTS: Study findings revealed that accurate pain knowledge and pain threshold were higher amongst children in the experimental group compared to the control group. In contrast with expectations, no main effects of the video intervention were observed for experienced pain intensity, pain-related fear and catastrophic worry. Moderation analyses indicated that the video intervention contributed, in comparison with the control condition, to higher levels of pain knowledge amongst younger children only and to higher pain thresholds amongst boys only. CONCLUSIONS: Further investigation is needed to optimize pain educational video interventions and to determine whether more beneficial outcomes can be found in clinical (i.e. non-experimental) situations and in children with persistent or recurring pain problems. SIGNIFICANCE: Examining the impact of pain educational interventions within a non-clinical setting is deemed particularly important given that adaptive pain coping strategies likely play an important role in preventing the development and maintenance of future maladaptive pain-related behaviour. Further, study findings provide preliminary evidence of baseline and demographic (i.e. age and sex) characteristics explaining differences in the effect of a pain educational video intervention in pain knowledge and pain-related experiences during experimental pain.

Lifestyle and Pain following Cancer: State-of-the-Art and Future Directions.

This review discusses chronic pain, multiple modifiable lifestyle factors, such as stress, insomnia, diet, obesity, smoking, alcohol consumption and physical activity, and the relationship between these lifestyle factors and pain after cancer. Chronic pain is known to be a common consequence of cancer treatments, which considerably impacts cancer survivors' quality of life when it remains untreated. Improvements in lifestyle behaviour are known to reduce mortality, comorbid conditions (i.e., cardiovascular diseases, other cancer, and recurrence) and cancer-related side-effects (i.e., fatigue and psychological issues). An inadequate stress response plays an important role in dysregulating the body's autonomic, endocrine, and immune responses, creating a problematic back loop with pain. Next, given the high vulnerability of cancer survivors to insomnia, addressing and treating those sleep problems should be another target in pain management due to its capacity to increase hyperalgesia. Furthermore, adherence to a healthy diet holds great anti-inflammatory potential for relieving pain after cancer. Additionally, a healthy diet might go hand in hand with weight reduction in the case of obesity. Consuming alcohol and smoking have an acute analgesic effect in the short-term, with evidence lacking in the long-term. However, this acute effect is outweighed by other harms on cancer survivors' general health. Last, informing patients about the benefits of an active lifestyle and reducing a sedentary lifestyle after cancer treatment must be emphasised when considering the proven benefits of physical activity in this population. A multimodal approach addressing all relevant lifestyle factors together seems appropriate for managing comorbid conditions, side-effects, and chronic pain after cancer. Further research is needed to evaluate whether modifiable lifestyle factors have a beneficial influence on chronic pain among cancer survivors.

The Impact of Parental Pain-attending and Non-pain-attending Responses on Child Pain Behavior in the Context of Cancer-related Painful Procedures: The Moderating Role of Parental Self-oriented Distress.

OBJECTIVES: Literature has demonstrated inconsistent findings regarding the impact of parental responses on child pain-related outcomes. Yet, research into factors that may underlie inconsistent findings regarding the variable impact of parental responses is lacking. The current study investigated the moderating role of parental distress in understanding the impact of parental pain-attending (eg, reassuring the child) and non-pain-attending (eg, distracting the child with humor) responses on child pain behavior (eg, crying). METHODS: Children (18 y and younger) with leukemia, undergoing a lumbar puncture (LP) and/or bone marrow aspiration procedure, and one of their parents, were recruited from the Pediatric Ghent University Hospital. Parent-child interactions were videotaped after the procedure allowing coding of parental responses and child pain behavior. Parents self-reported on experienced personal distress. RESULTS: Participants consisted of 42 children (24 boys, 18 girls) with leukemia and one of their parents. Children were 0.6 to 15 (7.08±4.39) years old. Findings indicated a positive association between parental pain-attending and child pain behavior, but only when parents reported high levels of distress (ß=0.56, P=0.001). No association was observed for parents reporting low levels of distress (ß=-0.09, ns). Parental non-pain-attending responses contributed to lower child pain behavior (ß=-0.24, P=0.045), independently of parental distress (ß=-0.07, ns). DISCUSSION: The current findings point to the moderating role of parental distress in understanding the impact of parental responses on child pain behavior and highlight the importance of interventions targeting parental emotion regulation to promote optimal child pain outcomes.

Pain Neuroscience Education for Children with Functional Abdominal Pain Disorders: A Randomized Comparative Pilot Study.

This article explores the effectiveness of a newly developed Pain Neuroscience Education program for children (PNE4Kids) with functional abdominal pain disorder (FAPD). Children (6-12 years) with FAPD were randomly assigned to 1) the experimental group (n = 14), participating in one hypnotherapy session (i.e., usual care) and one additional PNE4Kids session, or 2) the control group (n = 14), participating in two hypnotherapy sessions. Parental pain catastrophizing, the child's functional disability (parental-proxy), pain-related fear (parent-proxy) and pain intensity, were assessed at baseline and one and three weeks after each therapy session. Pressure algometry and a conditioned pain modulation paradigm were performed at baseline and three weeks after completion of the last therapy session. Parents from both the experimental as well as the control group showed significantly less parental pain catastrophizing (p < 0.01). Children showed significantly less functional disability (p < 0.05), pain-related fear (p < 0.01) and local pressure pain sensitivity (p < 0.05) at short-term follow-up (three weeks after last intervention) in both groups. No significant (p > 0.05) between-group differences were found. Hypnotherapy combined with PNE4Kids did not result in better clinical outcomes compared to hypnotherapy alone. Study limitations include the application of one single PNE4Kids session and the short follow-up time.

Best Evidence Rehabilitation for Chronic Pain Part 3: Low Back Pain.

Chronic Low Back Pain (CLBP) is a major and highly prevalent health problem. Given the high number of papers available, clinicians might be overwhelmed by the evidence on CLBP management. Taking into account the scale and costs of CLBP, it is imperative that healthcare professionals have access to up-to-date, evidence-based information to assist them in treatment decision-making. Therefore, this paper provides a state-of-the-art overview of the best evidence non-invasive rehabilitation for CLBP. Taking together up-to-date evidence from systematic reviews, meta-analysis and available treatment guidelines, most physically inactive therapies should not be considered for CLBP management, except for pain neuroscience education and spinal manipulative therapy if combined with exercise therapy, with or without psychological therapy. Regarding active therapy, back schools, sensory discrimination training, proprioceptive exercises, and sling exercises should not be considered due to low-quality and/or conflicting evidence. Exercise interventions on the other hand are recommended, but while all exercise modalities appear effective compared to minimal/passive/conservative/no intervention, there is no evidence that some specific types of exercises are superior to others. Therefore, we recommend choosing exercises in line with the patient's preferences and abilities. When exercise interventions are combined with a psychological component, effects are better and maintain longer over time.

Endogenous pain modulation in children with functional abdominal pain disorders.

Functional abdominal pain disorders (FAPDs) are common among young individuals. To date, relatively little is known regarding the function of the endogenous analgesic mechanisms in this vulnerable group. Therefore, this case-control study aimed to compare conditioned pain modulation (CPM), pressure algometry, and psychosocial variables in 39 young children (aged 6-12 years) with FAPD and 36 age- and sex-matched pain-free controls. Pressure algometry was used to assess pressure pain thresholds (PPTs) at both symptomatic (umbilicus) as remote (trapezius and tibia) test sites. Conditioned pain modulation was recorded as an increase in the PPT at the trapezius test site in response to experimental conditioning pain imposed by the cold pressor task (12 ± 1°C). The assessors were blinded to the diagnoses. Parent-proxy and/or self-reported questionnaires were used to assess child's pain intensity, functional disability, pain-related fear, and parental pain catastrophizing. Compared with pain-free controls, young children with FAPD showed lower PPTs at all test sites (P < 0.05), a lower CPM response (P = 0.02), more functional disability (P < 0.001), and pain-related fear (P < 0.001). Parents of children with FAPD catastrophized more about their child's pain than parents of healthy children (P < 0.001). No sex differences were found for the experimental pain measurements (P > 0.05), nor was there a significant correlation between the child- and parent-reported questionnaires and the CPM effect (P > 0.05). In summary, young children with FAPD demonstrated secondary hyperalgesia and decreased functioning of endogenous analgesia.