Bio

Honors & Awards


  • Postdoctoral Support Grant ($150,000), Stanford Maternal and Child Health Research Institute (2019-2021)
  • Marian R. Stuart Project Grant on the Connection Between Mental and Physical Health ($18,500), American Psychological Foundation (2019-2020)
  • Project Grant: Building Resilience and Values through E-health (BRAVE) ($80,000), Lucile Packard Foundation for Children?s Health Auxiliaries Endowment Fund (2019-2020)
  • International Collaboration Award ($5000), Society of Pediatric Psychology (2017-2018)
  • Research Training Fellowship ($180,000), Action Medical Research for Children (2013-2016)

Professional Education


  • Doctor of Philosophy, University of Oxford (2017)
  • MSc in Psychological Research, University of Oxford (2011)

Stanford Advisors


Research & Scholarship

Lab Affiliations


Publications

All Publications


  • Rapid identification and clinical indices of fear-avoidance in youth with chronic pain. Pain Heathcote, L. C., Bhandari, R. P., Timmers, I., Harrison, L. E., Simons, L. E. 2019

    Abstract

    Pain-related fear and avoidance are increasingly demonstrated to play an important role in adult and childhood chronic pain. The Fear of Pain Questionnaire for Children (FOPQC) is a 24-item measure of pain-related fear-avoidance in youth that has demonstrated good indices of reliability and validity, treatment responsiveness, and associations with brain circuitry alterations. This study describes the development and psychometric examination of the FOPQC-SF, a short form of the original measure. We selected 10 items for the short form that best represented the content and two-factor (Fear and Avoidance) structure of the original measure from a cohort of 613 youth (Mage = 14.7 years) with chronic pain. Next, confirmatory factor analyses from a second sample of 526 youth (Mage = 14.7 years) with chronic pain who completed the FOPQC-SF supported the original two-factor model but indicated that one item should be moved to the avoidance subscale. The FOPQC-SF demonstrates strong internal consistency and moderate-to-strong construct and criterion validity. Three-month test-retest reliability estimates (N=94) were strong and there was preliminary evidence of responsivity to change. To aid integration into intervention trials and clinical practice, we provide clinical reference points and a criterion to assess reliable change. The short form could be used for rapid identification of pain-related fear and avoidance in youth during clinic evaluations, and is optimized for clinical registries.

    View details for DOI 10.1097/j.pain.0000000000001742

    View details for PubMedID 31688496

  • Assessing the content specificity of interpretation biases in community adolescents with persistent and interfering pain. Pain Lau, J. Y., Badaoui, M., Meehan, A. J., Heathcote, L. C., Barker, E. D., Rimes, K. A. 2019

    Abstract

    The tendency to select threatening over benign interpretations of ambiguous bodily sensations and cues characterises young people with chronic pain. However, previous studies disagree over whether these biases extend to non-bodily harm situations such as social evaluation. Understanding the content of these biases is crucial to the development of pain management strategies seeking to modify such biases. Two hundred and forty-three young people aged 16-19 years completed an expanded version of the Adolescent Interpretation of Bodily Threat task. Using a factor-analytic approach, we removed items that did not consistently associate with bodily harm or social evaluation. Next, we examined whether the variance underlying negative and benign interpretations of bodily harm and social evaluation situations were best represented as a common factor (i.e., one-factor model), two distinct factors (i.e., two-factor model), or one common and two distinct factors (i.e., two-factor bi-factor model) in all adolescents. We then compared youth with and without persistent and impairing pain on factor scores derived from the best-fitting model. While negative interpretations of bodily harm and social evaluation situations emerged as distinct factors, benign interpretations across situations were best captured by a common factor and two situation-specific factors (i.e., bifactor model). Group comparisons showed that young people with moderate-to-high pain interference were more likely to endorse negative interpretations across all situations, and less likely to manifest a general benign interpretational style, than youth without interfering pain although some of these group differences were explained by co-occurring anxiety and depressive symptoms. Replication of these findings is needed.

    View details for DOI 10.1097/j.pain.0000000000001723

    View details for PubMedID 31634340

  • Somatic Symptoms in Pediatric Patients With Chronic Pain: Proposed Clinical Reference Points for the Children's Somatic Symptoms Inventory (Formerly the Children's Somatization Inventory) JOURNAL OF PAIN Stone, A. L., Walker, L. S., Heathcote, L. C., Hernandez, J., Basch, M. C., Wilson, A. C., Simons, L. E. 2019; 20 (8): 932?40
  • When "A Headache is Not Just a Headache": A Qualitative Examination of Parent and Child Experiences of Pain After Childhood Cancer. Psycho-oncology Tutelman, P. R., Chambers, C. T., Urquhart, R., Fernandez, C. V., Heathcote, L. C., Noel, M., Flanders, A., Guilcher, G. M., Schulte, F., Stinson, J. N., MacLeod, J., Stern, M. 2019

    Abstract

    OBJECTIVE: Today over 80% of children diagnosed with cancer are expected to survive. Despite the high prevalence of pain associated with the diagnosis and treatment of childhood cancer, there is a limited understanding of how having cancer shapes children's experience and meaning of pain after treatment has ended. This study addresses this gap by exploring childhood cancer survivors' (CCS') experiences of pain from their perspective and the perspective of their parents.METHODS: Twenty semi-structured interviews were completed with CCS (50% female; mean age = 13.20 years, range = 8-17 years) and their parents (90% mothers). Data were analyzed using Interpretive Phenomenological Analysis.RESULTS: Analyses revealed three superordinate themes present in the data: (1) pain is a changed experience after childhood cancer; (2) new or ambiguous pains may be interpreted by CCS and parents as a threat of disease recurrence, late effects, or a secondary cancer; and (3) pain interpretation occurs within the broader context of how CCS and parents appraise their cancer experience. Parents generally appraised their child's cancer and pain as more threatening and were influential in guiding their child's interpretations.CONCLUSIONS: The cancer experience played an important role in shaping CCS' and their parents' experience and interpretation of pain in survivorship. This study provides novel data to inform the development and refinement of new and existing conceptual models of pain and symptom perception after cancer. The results also point to key areas for future investigation and clinical intervention to address the issue of pain in cancer survivorship.

    View details for DOI 10.1002/pon.5170

    View details for PubMedID 31276614

  • "My Surgical Success": Effect of a Digital Behavioral Pain Medicine Intervention on Time to Opioid Cessation After Breast Cancer Surgery-A Pilot Randomized Controlled Clinical Trial. Pain medicine (Malden, Mass.) Darnall, B. D., Ziadni, M. S., Krishnamurthy, P., Flood, P., Heathcote, L., Mackey, I. G., Taub, C. J., Wheeler, A. 2019

    Abstract

    OBJECTIVE: This study aims to assess the feasibility of digital perioperative behavioral pain medicine intervention in breast cancer surgery and evaluate its impact on pain catastrophizing, pain, and opioid cessation after surgery.DESIGN AND SETTING: A randomized controlled clinical trial was conducted at Stanford University (Palo Alto, CA, USA) comparing a digital behavioral pain medicine intervention ("My Surgical Success" [MSS]) with digital general health education (HE).PARTICIPANTS: A convenience sample of 127 participants were randomized to treatment group. The analytic sample was 68 patients (N=36 MSS, N=32 HE).MAIN OUTCOMES: The primary outcome was feasibility and acceptability of a digital behavioral pain medicine intervention (80% threshold for acceptability items). Secondary outcomes were pain catastrophizing, past seven-day average pain intensity, and time to opioid cessation after surgery for patients who initiated opioid use.RESULTS: The attrition rate for MSS intervention (44%) was notably higher than for HE controls (18%), but it was lower than typical attrition rates for e-health interventions (60-80%). Despite greater attrition for MSS, feasibility was demonstrated for the 56% of MSS engagers, and the 80% threshold for acceptability was met. We observed a floor effect for baseline pain catastrophizing, and no significant group differences were found for postsurgical pain catastrophizing or pain intensity. MSS was associated with 86% increased odds of opioid cessation within the 12-week study period relative to HE controls (hazard ratio = 1.86, 95% confidence interval = 1.12-3.10, P=0.016).CONCLUSIONS: Fifty-six percent of patients assigned to MSS engaged with the online platform and reported high satisfaction. MSS was associated with significantly accelerated opioid cessation after surgery (five-day difference) with no difference in pain report relative to controls. Perioperative digital behavioral pain medicine may be a low-cost, accessible adjunct that could promote opioid cessation after breast cancer surgery.

    View details for PubMedID 31087093

  • Response to learned threat in youth with chronic pain Simons, L., Heathcote, L. C., Timmers, I., Alto, P., Borsook, D. LIPPINCOTT WILLIAMS & WILKINS. 2019: A204
  • Commentary: From Symptoms to Sensations: Moving Toward a Normal Psychology of Somatic Experiences in Youth. Journal of pediatric psychology Heathcote, L. C. 2019

    View details for DOI 10.1093/jpepsy/jsz028

    View details for PubMedID 31329910

  • Pain neuroscience education on YouTube PEERJ Heathcote, L. C., Pate, J. W., Park, A. L., Leake, H. B., Moseley, G., Kronman, C. A., Fischer, M., Timmers, I., Simons, L. E. 2019; 7: e6603

    Abstract

    The Internet in general, and YouTube in particular, is now one of the most popular sources of health-related information. Pain neuroscience education has become a primary tool for managing persistent pain, based in part on the discovery that information about pain can change pain. Our objective was to examine the availability, characteristics, and content of YouTube videos that address the neuroscience of pain.We conducted a systematic review of videos on YouTube using the search terms "pain education", "what is pain", and "pain brain" in January 2018. Videos were included if they were in English, were under 10 minutes long, and included information on the neuroscience of pain. Videos were coded for (i) descriptive characteristics (e.g., number of views, duration on YouTube), (ii) source and style, (iii) whether or not they addressed seven pre-determined target concepts of pain neuroscience education (e.g., 'Pain is not an accurate marker of tissue state'), and (iv) how engaging they were.We found 106 unique videos that met the inclusion criteria. The videos ranged from having four views to over five million views (Mdn = 1,163 views), with the three most highly viewed videos accounting for 75% of the total views. Animated videos were much more highly viewed than non-animated videos. Only a small number of videos had been posted by a clearly-identifiable reputable source such as an academic or medical institution (10%), although a number of videos were posted by healthcare professionals and professional medical societies. For a small number of videos (7%), the source was unclear. We found 17 videos that addressed at least one target concept of pain neuroscience science education, only nine of which were considered to be at least somewhat engaging. The target concept 'Pain is a brain output' was considered to be well addressed by the most videos (N = 11), followed by 'Pain is a protector' (N = 10). We found only one video that adequately addressed all seven target concepts of pain neuroscience education.YouTube contains a variety of videos that practitioners, patients, and families may view to access pain neuroscience education information. A small portion of these videos addressed one or more target concepts of pain neuroscience education in an engaging manner. It is yet to be determined to what extent patients are able to learn information from these videos, to what extent the videos promote behavior change, and thus to what extent the videos may be useful for clinical practice.

    View details for PubMedID 30923652

  • Somatic symptoms in pediatric patients with chronic pain: Proposed clinical reference points for the Children's Somatic Symptoms Inventory (formerly Children's Somatization Inventory). The journal of pain : official journal of the American Pain Society Stone, A. L., Walker, L. S., Heathcote, L. C., Hernandez, J. M., Basch, M. C., Wilson, A. C., Simons, L. E. 2019

    Abstract

    Among youth with chroic pain, elevated somatic symptoms across multiple body systems have been associated with greater emotional distress and functional disability and could represent poor adaptation to pain. The Children's Somatic Symptoms Inventory (formerly the Children's Somatization Inventory) is commonly used to assess somatic symptoms in children. However, no studies have evaluated the clinical utility of the measure in the assessment of pediatric patients with chronic pain. This study evaluated the factor structure and clinical relevance of the 24-item Children's Somatic Symptoms Inventory (CSSI-24) in youth (n?=?1150) with mixed chronic pain complaints presenting to a tertiary pain clinic. CSSI-24 total scores were equal or superior to factor scores as indicators of patients' clinical characteristics (functional disability, pain catastrophizing, fear of pain, anxiety and depressive symptoms) and parental catastrophizing and protective responses. Tertile-derived clinical reference points for the CSSI-24 total score (<18: low, 19 - 31: moderate, ? 32: high) significantly differed on measures of clinical characteristics and parent factors. Controlling for age, sex, pain intensity and primary pain complaint, the high somatic symptoms group exhibited significantly greater health care utilization compared to the moderate and low groups. Assessment of somatic symptoms in pediatric patients with chronic pain may provide useful information regarding patients' psychosocial risk and tendency to access health services. Perspective: Clinical reference points based on the CSSI-24 total scores meaningfully differentiated youth with chronic pain on measures of emotional distress, functioning, parent catastrophizing and protective responses, and health care utilization. Assessing somatic symptoms could provide useful information regarding a pediatric patient's psychosocial risk, tendency to access health services, and need for enhanced care coordination.

    View details for PubMedID 30771592

  • Pharmacological interventions for chronic pain in children: an overview of systematic reviews. Pain Eccleston, C., Fisher, E., Cooper, T. E., Grégoire, M. C., Heathcote, L. C., Krane, E., Lord, S. M., Sethna, N. F., Anderson, A. K., Anderson, B., Clinch, J., Gray, A. L., Gold, J. I., Howard, R. F., Ljungman, G., Moore, R. A., Schechter, N., Wiffen, P. J., Wilkinson, N. M., Williams, D. G., Wood, C., van Tilburg, M. A., Zernikow, B. 2019; 160 (8): 1698?1707

    Abstract

    We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic noncancer pain (CNCP) or chronic cancer-related pain (CCRP). We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE, and DARE for systematic reviews from inception to March 2018. We conducted reference and citation searches of included reviews. We included children (0-18 years of age) with CNCP or CCRP. We extracted the review characteristics and primary outcomes of ?30% participant-reported pain relief and patient global impression of change. We sifted 704 abstracts and included 23 systematic reviews investigating children with CNCP or CCRP. Seven of those 23 reviews included 6 trials that involved children with CNCP. There were no randomised controlled trials in reviews relating to reducing pain in CCRP. We were unable to combine data in a meta-analysis. Overall, the quality of evidence was very low, and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42018086900.

    View details for DOI 10.1097/j.pain.0000000000001609

    View details for PubMedID 31335640

  • Digitally enabled patient-reported outcome measures in cancer care - Authors' reply. The Lancet. Oncology Heathcote, L. C., Goldberg, D. S., Eccleston, C., Spunt, S. L., Simons, L. E., Sharpe, L., Earp, B. D. 2019; 20 (1): e3

    View details for PubMedID 30614475

  • Pain Education for Adolescents and Young Adults Living Beyond Cancer: An Interdisciplinary Meeting Report. Journal of adolescent and young adult oncology Heathcote, L. C., Allen, J. M., Gunn, K. M., Fox, S., Harvie, D. S., Olver, I., Skinner, I. W., Smith, A. G., Stanton, T. R., Whitford, H. S., Moseley, G. L. 2019

    Abstract

    Pain is an understudied and undertreated consequence of cancer survival. Pain education is now a recommended treatment approach for persistent non-cancer pain, yet it has not been well applied to the context of adolescent and young adult (AYA) cancer survival. In March 2018, an interdisciplinary meeting was held in Adelaide, South Australia to set a research agenda for pain education in AYA cancer survivors. We identified that AYAs with persistent pain and those with heightened pain-related fear have the potential to benefit from pain education. We identified a number of unique challenges of engaging AYA survivors in pain education, and point towards future research directions.

    View details for DOI 10.1089/jayao.2019.0047

    View details for PubMedID 31150299

  • Pharmacological interventions for chronic pain in children: an overview of systematic reviews. Pain Eccleston, C., Fisher, E., Cooper, T. E., Grégoire, M. C., Heathcote, L. C., Krane, E., Lord, S. M., Sethna, N. F., Anderson, A. K., Anderson, B., Clinch, J., Gray, A. L., Gold, J. I., Howard, R. F., Ljungman, G., Moore, R. A., Schechter, N., Wiffen, P. J., Wilkinson, N. M., Williams, D. G., Wood, C., van Tilburg, M. A., Zernikow, B. 2019

    Abstract

    We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic non-cancer pain or chronic cancer-related pain. We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE and DARE for systematic reviews from inception to March 2018. We conducted reference and citation searches of included reviews. We included children (0-18 years of age) with chronic non-cancer pain or chronic cancer-related pain. We extracted the review characteristics and primary outcomes of ?30% participant-reported pain relief and patient global impression of change. We sifted 704 abstracts and included 23 systematic reviews investigating children with chronic non-cancer pain or chronic cancer-related pain. Seven of those 23 reviews included six trials that involved children with chronic non-cancer pain. There were no RCTs in reviews relating to reducing pain in chronic cancer-related pain. We were unable to combine data in a meta-analysis. Overall, the quality of evidence was very low and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42017081205. A video accompanying this abstract is available online as Supplemental Digital Content at http://links.lww.com/PAIN/A797.

    View details for DOI 10.1097/j.pain.0000000000001609

    View details for PubMedID 31107413

  • The interaction between stress and chronic pain through the lens of threat learning. Neuroscience and biobehavioral reviews Timmers, I., Quaedflieg, C. W., Hsu, C., Heathcote, L. C., Rovnaghi, C. R., Simons, L. E. 2019

    Abstract

    Stress and pain are interleaved at multiple levels - interacting and influencing each other. Both are modulated by psychosocial factors including fears, beliefs, and goals, and are served by overlapping neural substrates. One major contributing factor in the development and maintenance of chronic pain is threat learning, with pain as an emotionally-salient threat - or stressor. Here, we argue that threat learning is a central mechanism and contributor, mediating the relationship between stress and chronic pain. We review the state of the art on (mal)adaptive learning in chronic pain, and on effects of stress and particularly cortisol on learning. We then provide a theoretical integration of how stress may affect chronic pain through its effect on threat learning. Prolonged stress, as may be experienced by patients with chronic pain, and its resulting changes in key brain networks modulating stress responses and threat learning, may further exacerbate these impairing effects on threat learning. We provide testable hypotheses and suggestions for how this integration may guide future research and clinical approaches in chronic pain.

    View details for DOI 10.1016/j.neubiorev.2019.10.007

    View details for PubMedID 31622630

  • Is Empathy for Pain Unique in Its Neural Correlates? A Meta-Analysis of Neuroimaging Studies of Empathy FRONTIERS IN BEHAVIORAL NEUROSCIENCE Timmers, I., Park, A. L., Fischer, M. D., Kronman, C. A., Heathcote, L. C., Hernandez, J., Simons, L. E. 2018; 12
  • Advancing shared decision making for symptom monitoring in people living beyond cancer LANCET ONCOLOGY Heathcote, L. C., Goldberg, D. S., Eccleston, C., Spunt, S. L., Simons, L. E., Sharpe, L., Earp, B. D. 2018; 19 (10): E556?E563

    Abstract

    Wellbeing after successful cancer treatment depends on more than merely reducing the risk of disease recurrence. Cancer survival can be characterised by uncertainty, fear, and the interpretation of bodily sensations as potentially symptomatic of cancer recurrence. This fear can lead to over-vigilance about bodily sensations and precautionary visits to the doctor, both of which can increase the chance of early detection but can also increase anxiety and decrease quality of life. In this Personal View, we consider the medical, psychological, and ethical issues related to the practice of self-directed symptom monitoring after completion of cancer treatment, focusing on the role of doctor-patient communication. We ask how clinicians can account for the plurality of values that patients might have when it comes to deciding on how to manage and respond to experiences of post-cancer symptoms. We advocate a shared decision-making approach that incorporates the assessment of an individual's cancer recurrence risks as well as psychosocial considerations regarding fear of cancer recurrence and mental health. We aim to raise awareness of the potential quality-of-life implications of symptom-monitoring practices, emphasising the need for a balance between physical and psychological health in people living beyond cancer.

    View details for PubMedID 30303128

  • Precipitating events in child and adolescent chronic musculoskeletal pain. Pain reports Becker, A. J., Heathcote, L. C., Timmers, I., Simons, L. E. 2018; 3 (Suppl 1): e665

    Abstract

    Introduction: The epidemiology of chronic pain in youth has been increasingly documented over the past decade. However, the precipitating events associated with the onset of pediatric chronic pain are not well studied.Objectives: Understanding the events that precede the onset of pain, and are reported by patients as germane to the early stages of their pain, may add one piece to the puzzle of the causal etiology of pediatric chronic pain disorders.Methods: We conducted a retrospective chart review of 320 young people attending a tertiary care chronic pain clinic with musculoskeletal chronic pain.Results: Approximately two-thirds of patients reported a precipitating event for their pain; injury was the most commonly reported event, followed by a chronic disease, then an infection or illness. Surgery was the least commonly reported event. About one-third of patients did not report any precipitating event for their pain. Patients with neuropathic pain were even more likely to report a precipitating event compared to those with localized and diffuse musculoskeletal pain. Patients with localized musculoskeletal pain and neuropathic pain were most likely to report an injury, whereas patients with diffuse musculoskeletal pain were most likely to report a chronic disease. We found little to no evidence that the presence or type of precipitating event was associated with patients' psychological or physical functioning.Conclusion: This study adds to the epidemiological evidence base for pediatric chronic pain disorders.

    View details for PubMedID 30324167

  • Parent Attributions of Ambiguous Symptoms in Their Children: A Preliminary Measure Validation in Parents of Children with Chronic Pain. Children (Basel, Switzerland) Heathcote, L. C., Williams, S. E., Smith, A. M., Sieberg, C. B., Simons, L. E. 2018; 5 (6)

    Abstract

    How parents attribute cause to their child’s physical symptoms is likely important in understanding how the parent responds to the child, as well as the child’s health outcomes, especially within the context of chronic illness. Here, we adapt the Symptom Interpretation Questionnaire for parent report (SIQ-PR) and provide preliminary validation in a sample of parents of children with chronic pain (N = 311). Confirmatory factor analysis revealed that the SIQ-PR structure is consistent with the original measure, with three distinct attribution types: psychological (emotional/affective), somatic (illness/disease), and environmental (situational/transient) causes. All three subscales demonstrated satisfactory to good internal consistency, and temporal stability. Parents typically endorsed more than one attribution for each symptom, indicating that parents of children with chronic pain have a multidimensional interpretation of physical symptoms in their children. Further, parent psychological and somatic attributions, but not environmental attributions, were significantly associated with (i) parent protective responses towards their child, and (ii) the child’s self-reported somatic and psychological symptoms, indicating convergent and divergent validity. The SIQ-PR may be a useful measure for future studies investigating intergenerational and interpersonal models of pediatric chronic pain, and more broadly, to examine parent attributions of children’s ambiguous symptoms within the context of childhood chronic illness.

    View details for PubMedID 29899299

  • Cognitive Biases in Children and Adolescents With Chronic Pain: A Review of Findings and a Call for Developmental Research JOURNAL OF PAIN Lau, J. F., Heathcote, L. C., Beale, S., Gray, S., Jacobs, K., Wilkinson, N., Crombez, G. 2018; 19 (6): 589?98

    Abstract

    Cognitive biases that emphasize bodily harm, injury, and illness could play a role in the maintenance of chronic pain by facilitating fear and avoidance. Whereas extensive research has established attention, interpretation, and memory biases in adults with chronic pain, far less is known about these same biases in children and adolescents with pain. Studying cognitive biases in attention, interpretation, and memory in relation to pain occurring in youth is important because youth is a time when pain can first become chronic, and when relationships between cognitive biases and pain outcomes emerge and stabilize. Thus, youth potentially offers a time window for the prevention of chronic pain problems. In this article, we summarize the growing corpus of data that have measured cognitive biases in relation to pediatric pain. We conclude that although biases in attention, interpretation, and memory characterize children and adolescents with varying pain experiences, questions regarding the direction, magnitude, nature, and role of these biases remain. We call for independent extension of cognitive bias research in children and adolescents, using well powered longitudinal studies with wide age ranges and psychometrically sound experimental measures to clarify these findings and any developmental trends in the links between cognitive biases and pain outcomes.This article provides a rationale for the theoretical and practical importance of studying the role of cognitive biases in children and adolescents with chronic pain, which has to date, been relatively understudied. Existing findings are reviewed critically, and recommendations for future research are offered.

    View details for PubMedID 29374535

  • Topical Review: Pain in Survivors of Pediatric Cancer: Applying a Prevention Framework JOURNAL OF PEDIATRIC PSYCHOLOGY Stone, A. L., Karlson, C. W., Heathcote, L. C., Rosenberg, A. R., Palermo, T. M. 2018; 43 (3): 237?42

    Abstract

    To apply a biopsychosocial framework to understand factors influencing pain in survivors of pediatric cancer to inform pain prevention efforts and highlight the need for interdisciplinary care.This topical review draws from both pediatric cancer survivorship research and chronic noncancer pain research to illustrate how components of a preventative model can be applied to pain in survivorship.Pain is a common experience among long-term survivors of pediatric cancer. The pain experience in survivorship can be conceptualized in terms of biological disease and treatment factors, cognitive and affective factors, and social and contextual factors. We review literature pertinent to each of these biopsychosocial factors and tailor an existing public health prevention framework for pain in survivors of pediatric cancer.Classifying survivors of pediatric cancer into pain risk categories based on their daily experiences of pain, pain-related functional impairment, and distress could help guide the implementation of pain-related prevention and intervention strategies in this population. Future research is needed to establish the efficacy of screening measures to identify patients in need of psychosocial pain and pain-related fear management services, and interdisciplinary pediatric chronic pain management programs in survivors of pediatric cancer.

    View details for PubMedID 29048571

  • Assessment of Pain Anxiety, Pain Catastrophizing, and Fear of Pain in Children and Adolescents With Chronic Pain: A Systematic Review and Meta-Analysis JOURNAL OF PEDIATRIC PSYCHOLOGY Fisher, E., Heathcote, L. C., Eccleston, C., Simons, L. E., Palermo, T. M. 2018; 43 (3): 314?25

    Abstract

    To conduct a systematic review of pain anxiety, pain catastrophizing, and fear of pain measures psychometrically established in youth with chronic pain. The review addresses three specific aims: (1) to identify measures used in youth with chronic pain, summarizing their content, psychometric properties, and use; (2) to use evidence-based assessment criteria to rate each measure according to the Society of Pediatric Psychology (SPP) guidelines; (3) to pool data across studies for meta-analysis of shared variance in psychometric performance in relation to the primary outcomes of pain intensity, disability, generalized anxiety, and depression.We searched Medline, Embase, PsycINFO, and relevant literature for possible studies to include. We identified measures studied in youth with chronic pain that assessed pain anxiety, pain catastrophizing, or fear of pain and extracted the item-level content. Study and participant characteristics, and correlation data were extracted for summary and meta-analysis, and measures were rated using the SPP evidence-based assessment criteria.Fifty-four studies (84 papers) met the inclusion criteria, including seven relevant measures: one assessed pain anxiety, three pain catastrophizing, and three fear of pain. Overall, five measures were rated as "well established." We conducted meta-analyses on four measures with available data. We found significant positive correlations with the variables pain intensity, disability, generalized anxiety, and depression.Seven measures are available to assess pain anxiety, pain catastrophizing, and fear of pain in young people with chronic pain, and most are well established. We present implications for practice and directions for future research.

    View details for PubMedID 29049813

  • Rapid Screening of Risk in Pediatric Headache: Application of the Pediatric Pain Screening Tool JOURNAL OF PEDIATRIC PSYCHOLOGY Heathcote, L. C., Rabner, J., Lebel, A., Hernandez, J. M., Simons, L. E. 2018; 43 (3): 243?51

    Abstract

    The current study examined the application of a screening tool to identify biopsychosocial risk factors and derive prognostic risk groups in children and adolescents with headache pain.Youth (n = 242, 8-17?years, 75.6% female) presenting for evaluation at a tertiary pediatric headache clinic completed the nine-item Pediatric Pain Screening Tool (PPST) as well as measures of functional disability, pain catastrophizing, fear of pain, anxiety, and depressive symptoms. In addition, 119 patients reported on functional disability at 2-month follow-up.The PPST demonstrated discriminant validity that ranged from fair to good for identifying significant disability and high emotional distress. Receiver operating characteristic curve analyses indicated that established cutoff scores were appropriate for the current sample, and thus participants were classified into low-risk (21%), medium-risk (31%), and high-risk (48%) groups. Only 1-6% of patients who met reference standard case status for disability and emotional distress were classified as low risk, whereas 64-90% of patients who met reference standard case status were classified as high risk, suggesting robust stratification.The nine-item PPST may be a useful tool for efficiently identifying young patients with headache who are at risk of poor outcomes, and effectively classifying them into risk groups that could drive stratified treatment directly targeting patient needs.

    View details for PubMedID 29048551

  • Attention bias modification training for adolescents with chronic pain: a randomized placebo-controlled trial PAIN Heathcote, L. C., Jacobs, K., Van Ryckeghem, D. L., Fisher, E., Eccleston, C., Fox, E., Lau, J. F. 2018; 159 (2): 239?51
  • Social interaction and pain: An arctic expedition SOCIAL SCIENCE & MEDICINE Block, P., Heathcote, L. C., Heyes, S. 2018; 196: 47?55

    Abstract

    Complex human behaviour can only be understood within its social environment. However, disentangling the causal links between individual outcomes and social network position is empirically challenging. We present a research design in a closed real-world setting with high-resolution temporal data to understand this interplay within a fundamental human experience - physical pain. Study participants completed an isolated 3-week hiking expedition in the Arctic Circle during which they were subject to the same variation in environmental conditions and only interacted amongst themselves. Adolescents provided daily ratings of pain and social interaction partners. Using longitudinal network models, we analyze the interplay between social network position and the experience of pain. Specifically, we test whether experiencing pain is linked to decreasing popularity (increasing isolation), whether adolescents prefer to interact with others experiencing similar pain (homophily), and whether participants are increasingly likely to report similar pain as their interaction partners (contagion). We find that reporting pain is associated with decreasing popularity - interestingly, this effect holds for males only. Further exploratory analyses suggest this is at least partly driven by males withdrawing from contact with females when in pain, enhancing our understanding of pain and masculinity. Contrary to recent experimental and clinical studies, we found no evidence of pain homophily or contagion in the expedition group.

    View details for PubMedID 29127852

  • Is Empathy for Pain Unique in Its Neural Correlates? A Meta-Analysis of Neuroimaging Studies of Empathy. Frontiers in behavioral neuroscience Timmers, I., Park, A. L., Fischer, M. D., Kronman, C. A., Heathcote, L. C., Hernandez, J. M., Simons, L. E. 2018; 12: 289

    Abstract

    Empathy is an essential component of our social lives, allowing us to understand and share other people's affective and sensory states, including pain. Evidence suggests a core neural network-including anterior insula (AI) and mid-cingulate cortex (MCC)-is involved in empathy for pain. However, a similar network is associated to empathy for non-pain affective states, raising the question whether empathy for pain is unique in its neural correlates. Furthermore, it is yet unclear whether neural correlates converge across different stimuli and paradigms that evoke pain-empathy. We performed a coordinate-based activation likelihood estimation (ALE) meta-analysis to identify neural correlates of empathy, assess commonalities and differences between empathy for pain and for non-pain negative affective states, and differences between pain-empathy evoking stimuli (i.e., facial pain expressions vs. acute pain inflictions) and paradigms (i.e., perceptual/affective vs. cognitive/evaluative paradigms). Following a systematic search, data from 128 functional brain imaging studies presenting whole-brain results of an empathy condition vs. baseline/neutral condition were extracted. Synthesizing neural correlates of empathy confirmed a core network comprising AI, MCC, postcentral gyrus, inferior parietal lobe, thalamus, amygdala, and brainstem. There was considerable overlap in networks for empathy for pain and empathy for non-pain negative affective states. Important differences also arose: empathy for pain uniquely activated bilateral mid-insula and more extensive MCC. Regarding stimuli, painful faces and acute pain inflictions both evoked the core empathy regions, although acute pain inflictions activated additional regions including medial frontal and parietal cortex. Regarding paradigms, both perceptual/affective and cognitive/evaluative paradigms recruited similar neural circuitry, although cognitive/evaluative paradigms activated more left MCC regions while perceptual/affective paradigms activated more right AI. Taken together, our findings reveal that empathy for pain and empathy for non-pain negative affective states share considerable neural correlates, particularly in core empathy regions AI and MCC. Beyond these regions, important differences emerged, limiting generalizability of findings across different affective/sensory states. Within pain-empathy studies, the core regions were recruited robustly irrespective of stimuli or instructions, allowing one to tailor designs according to specific needs to some extent, while ensuring activation of core regions.

    View details for PubMedID 30542272

    View details for PubMedCentralID PMC6277791

  • Attention bias modification training for adolescents with chronic pain: a randomized placebo-controlled trial. Pain Heathcote, L. C., Jacobs, K., Van Ryckeghem, D. M., Fisher, E., Eccleston, C., Fox, E., Lau, J. Y. 2018; 159 (2): 239?51

    Abstract

    Attention bias for pain-related information is theorised to maintain chronic pain, indicating that changing this bias could improve pain-related outcomes. Modifying attention biases in adolescents, when chronic pain often first emerges, may be particularly beneficial. We report here a randomized, placebo-controlled, parallel-group trial of attention bias modification (ABM) training in adolescents with chronic noncancer pain. Adolescent patients (N = 66) were randomly assigned to complete multiple sessions of dot-probe ABM training (N = 23), placebo training (N = 22), or no training (waitlist; N = 21) across a period of 4 weeks. Patients completed all assessments at a hospital-based pediatric pain clinic and completed all training at home. We examined the relative effects of ABM on attention bias and attention control, as well as pain symptomatology (primary outcome), pain catastrophizing, anxiety and depression symptoms, and functional disability (secondary outcomes) immediately after training and 3 months later. We found no evidence that ABM changed attention bias or attention control in comparison with placebo training or no training. We also found that pain and pain-related outcomes were no different for those undergoing ABM compared with placebo training or no training when tested immediately after training or 3 months later. Overall, we found no evidence to support the efficacy of dot-probe ABM for improving pain-related outcomes in adolescents with chronic pain. This study was registered on the NIHR Clinical Research Network Portfolio in August 2014 (UK Clinical Trials Gateway: CPMS 17251) and funded by a Research Training Fellowship awarded to Lauren Heathcote by Action Medical Research for Children.

    View details for PubMedID 28968342

  • Biased interpretations of ambiguous bodily threat information in adolescents with chronic pain. Pain Heathcote, L. C., Jacobs, K., Eccleston, C., Fox, E., Lau, J. Y. 2017; 158 (3): 471-478

    Abstract

    Adult patients with chronic pain are consistently shown to interpret ambiguous health and bodily information in a pain-related and threatening way. This interpretation bias may play a role in the development and maintenance of pain and disability. However, no studies have yet investigated the role of interpretation bias in adolescent patients with pain, despite that pain often first becomes chronic in youth. We administered the Adolescent Interpretations of Bodily Threat (AIBT) task to adolescents with chronic pain (N = 66) and adolescents without chronic pain (N = 74). Adolescents were 10 to 18 years old and completed the study procedures either at the clinic (patient group) or at school (control group). We found that adolescents with chronic pain were less likely to endorse benign interpretations of ambiguous pain and bodily threat information than adolescents without chronic pain, particularly when reporting on the strength of belief in those interpretations being true. These differences between patients and controls were not evident for ambiguous social situations, and they could not be explained by differences in anxious or depressive symptoms. Furthermore, this interpretation pattern was associated with increased levels of disability among adolescent patients, even after controlling for severity of chronic pain and pain catastrophizing. The current findings extend our understanding of the role and nature of cognition in adolescent pain, and provide justification for using the AIBT task in longitudinal and training studies to further investigate causal associations between interpretation bias and chronic pain.

    View details for DOI 10.1097/j.pain.0000000000000781

    View details for PubMedID 28067692

  • Pain and cancer survival: a cognitive-affective model of symptom appraisal and the uncertain threat of disease recurrence. Pain Heathcote, L. C., Eccleston, C. 2017

    View details for DOI 10.1097/j.pain.0000000000000872

    View details for PubMedID 28195857

  • Antidepressants for chronic non-cancer pain in children and adolescents (Protocol) Cochrane Database of Systematic Reviews Cooper, T. E., Heathcote, L. C., Clinch, J., Gold, J., Howard, R., Lord, S., Schechter, N., Wood, C., Wiffen, P. J. 2017; 2
  • Antiepileptic drugs for chronic non-cancer pain in children and adolescents COCHRANE DATABASE OF SYSTEMATIC REVIEWS Cooper, T. E., Wiffen, P. J., Heathcote, L. C., Clinch, J., Howard, R., Krane, E., Lord, S. M., Sethna, N., Schechter, N., Wood, C. 2017: CD012536

    Abstract

    Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as importantWe designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can occur in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) relating to genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and for other unknown reasons.Antiepileptic (anticonvulsant) drugs, which were originally developed to treat convulsions in people with epilepsy, have in recent years been used to provide pain relief in adults for many chronic painful conditions and are now recommended for the treatment of chronic pain in the WHO list of essential medicines. Known side effects of antiepileptic drugs range from sweating, headache, elevated temperature, nausea, and abdominal pain to more serious effects including mental or motor function impairment.To assess the analgesic efficacy and adverse events of antiepileptic drugs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews as well as online clinical trial registries.Randomised controlled trials, with or without blinding, by any route, treating chronic non-cancer pain in children and adolescents, comparing any antiepileptic drug with placebo or an active comparator.Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods if data were available. We assessed the evidence using GRADE and created two 'Summary of findings' tables.We included two studies with a total of 141 participants (aged 7 to 18 years) with chronic neuropathic pain, complex regional pain syndrome type 1 (CRPS-I), or fibromyalgia. One study investigated pregabalin versus placebo in participants with fibromyalgia (107 participants), and the other study investigated gabapentin versus amitriptyline in participants with CRPS-I or neuropathic pain (34 participants). We were unable to perform any quantitative analysis.Risk of bias for the two included studies varied, due to issues with randomisation (low to unclear risk), blinding of outcome assessors (low to unclear risk), reporting bias (low to unclear risk), the size of the study populations (high risk), and industry funding in the 'other' domain (low to unclear risk). We judged the remaining domains of sequence generation, blinding of participants and personnel, and attrition as low risk of bias. Primary outcomesOne study (gabapentin 900 mg/day versus amitriptyline 10 mg/day, 34 participants, for 6 weeks) did not report our primary outcomes (very low-quality evidence).The second study (pregabalin 75 to 450 mg/day versus placebo 75 to 450 mg/day, 107 participants, for 15 weeks) reported no significant change in pain scores for pain relief of 30% or greater between pregabalin 18/54 (33.3%), and placebo 16/51 (31.4%), P = 0.83 (very low-quality evidence). This study also reported Patient Global Impression of Change, with the percentage of participants feeling "much or very much improved" with pregabalin 53.1%, and placebo 29.5% (very low-quality evidence).We downgraded the evidence by three levels to very low for one of two reasons: due to the fact that there was no evidence to support or refute the use of the intervention, or that there were too few data and the number of events was too small to be meaningful. Secondary outcomesIn one small study, adverse events were uncommon: gabapentin 2 participants (2 adverse events); amitriptyline 1 participant (1 adverse event) (6-week trial). The second study reported a higher number of adverse events: pregabalin 38 participants (167 adverse events); placebo 34 participants (132 adverse events) (15-week trial) (very low-quality evidence).Withdrawals due to adverse events were infrequent in both studies: pregabalin (4 participants), placebo (4 participants), gabapentin (2 participants), and amitriptyline (1 participant) (very low-quality evidence).Serious adverse events were reported in both studies. One study reported only one serious adverse event (cholelithiasis and major depression resulting in hospitalisation in the pregabalin group) and the other study reported no serious adverse events (very low-quality evidence).There were few or no data for our remaining secondary outcomes (very low-quality evidence).We downgraded the evidence by three levels to very low due to too few data and the fact that the number of events was too small to be meaningful.This review identified only two small studies, with insufficient data for analysis.As we could undertake no meta-analysis, we were unable to comment about efficacy or harm from the use of antiepileptic drugs to treat chronic non-cancer pain in children and adolescents. Similarly, we could not comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.We know from adult randomised controlled trials that some antiepileptics, such as gabapentin and pregabalin, can be effective in certain chronic pain conditions.We found no evidence to support or refute the use of antiepileptic drugs to treat chronic non-cancer pain in children and adolescents.

    View details for DOI 10.1002/14651858.CD012536.pub2

    View details for Web of Science ID 000408828100004

    View details for PubMedID 28779491

  • Non-steroidal anti-inflammatory drugs (NSAIDs) for cancer-related pain in children and adolescents COCHRANE DATABASE OF SYSTEMATIC REVIEWS Cooper, T. E., Heathcote, L. C., Anderson, B., Gregoire, M., Ljungman, G., Eccleston, C. 2017: CD012563

    Abstract

    Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for persisting pain in children acknowledge that pain in children is a major public health concern of high significance in most parts of the world. Views on children's pain have changed over time and relief of pain is now seen as important. In the past, pain was largely dismissed and was frequently left untreated, and it was assumed that children quickly forgot about painful experiences.We designed a suite of seven reviews in chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) to review the evidence for children's pain using pharmacological interventions.As one of the leading causes of mortality and morbidity for children and adolescents in the world today, childhood cancer (and its associated pain) is a major health concern. Specific mortality and morbidity data relating to children are not currently identified. All childhood cancer rates are on the rise; for example, in the USA approximately 10,380 children aged under 15 years were expected to be diagnosed with cancer by the end of 2016. However, with survival rates also increasing, over 80% of paediatric cancer patients are expected to survive for five years or more, thus identifying the need to address pain management in this population.Cancer pain in infants, children, and adolescents is primarily nociceptive pain with negative long term effects. Cancer-related pain is generally caused directly by the tumour itself such as compressing on the nerve or inflammation of the organs. Cancer-related pain generally occurs as a result of perioperative procedures, nerve damage caused by radiation or chemotherapy treatments, or mucositis. However, this review focused on pain caused directly by the tumour itself such as nerve infiltration, external nerve compression, and other inflammatory events.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammatory properties. They are commonly used within paediatric pain management. NSAIDs are currently licensed for use in western countries, however not approved for infants aged under three months. Primary adverse effects include gastrointestinal issues and possible renal impairment with long term use. Other adverse effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain.To assess the analgesic efficacy, and adverse events, of non-steroidal anti-inflammatory drugs (NSAIDs) used to treat cancer-related pain in children and adolescents aged from birth and 17 years, in any setting.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 21 February 2017. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.Randomised, double-blind trials of any dose, and any route, treating cancer-related pain in children and adolescents, comparing NSAIDs with placebo or an active comparator.Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a 'Summary of findings' table.No studies were eligible for inclusion in this review (very low quality evidence). We downgraded the quality of evidence by three levels due to the lack of data reported for any outcome.There is no evidence from randomised controlled trials that non-steroidal anti-inflammatory drugs (NSAIDs) reduce cancer-related pain in children and adolescents. This means that no reliance or conclusions can be made about efficacy or harm in the use of NSAIDs to treat chronic cancer-related pain in children and adolescents.

    View details for DOI 10.1002/14651858.CD012563.pub2

    View details for Web of Science ID 000406831100033

    View details for PubMedID 28737843

  • Antidepressants for chronic non-cancer pain in children and adolescents COCHRANE DATABASE OF SYSTEMATIC REVIEWS Cooper, T. E., Heathcote, L. C., Clinch, J., Gold, J. I., Howard, R., Lord, S. M., Schechter, N., Wood, C., Wiffen, P. J. 2017: CD012535

    Abstract

    Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Antidepressants have been used in adults for pain relief and pain management since the 1970s. The clinical impression from extended use over many years is that antidepressants are useful for some neuropathic pain symptoms, and that effects on pain relief are divorced and different from effects on depression; for example, the effects of tricyclic antidepressants on pain may occur at different, and often lower, doses than those on depression. Amitriptyline is one of the most commonly used drugs for treating neuropathic pain in the UK.To assess the analgesic efficacy and adverse events of antidepressants used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing any antidepressant with placebo or an active comparator.Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed the evidence using GRADE and created three 'Summary of findings' tables.We included four studies with a total of 272 participants (6 to 18 years of age) who had either chronic neuropathic pain, complex regional pain syndrome type 1, irritable bowel syndrome, functional abdominal pain, or functional dyspepsia. All of the studies were small. One study investigated amitriptyline versus gabapentin (34 participants), two studies investigated amitriptyline versus placebo (123 participants), and one study investigated citalopram versus placebo (115 participants). Due to a lack of available data we were unable to complete any quantitative analysis.Risk of bias for the four included studies varied, due to issues with randomisation and allocation concealment (low to unclear risk); blinding of participants, personnel, and outcome assessors (low to unclear risk); reporting of results (low to unclear risk); and size of the study populations (high risk). We judged the remaining domains, attrition and other potential sources of bias, as low risk of bias. Primary outcomesNo studies reported our primary outcomes of participant-reported pain relief of 30% or greater or 50% or greater (very low-quality evidence).No studies reported on Patient Global Impression of Change (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) as very low. We downgraded the quality of the evidence by three levels to very low because there was no evidence to support or refute. Secondary outcomesAll studies measured adverse events, with very few reported (11 out of 272 participants). All but one adverse event occurred in the active treatment groups (amitriptyline, citalopram, and gabapentin). Adverse events in all studies, across active treatment and comparator groups, were considered to be a mild reaction, such as nausea, dizziness, drowsiness, tiredness, and abdominal discomfort (very low-quality evidence).There were also very few withdrawals due to adverse events, again all but one from the active treatment groups (very low-quality evidence).No serious adverse events were reported across any of the studies (very low-quality evidence).There were few or no data for our remaining secondary outcomes (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) for these secondary outcomes as very low. We downgraded the quality of the evidence by three levels to very low due to too few data and the fact that the number of events was too small to be meaningful.We identified only a small number of studies with small numbers of participants and insufficient data for analysis.As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of antidepressants to treat chronic non-cancer pain in children and adolescents. Similarly, we cannot comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.There is evidence from adult randomised controlled trials that some antidepressants, such as amitriptyline, can provide some pain relief in certain chronic non-cancer pain conditions.There is no evidence from randomised controlled trials to support or refute the use of antidepressants to treat chronic non-cancer pain in children or adolescents.

    View details for DOI 10.1002/14651858.CD012535.pub2

    View details for Web of Science ID 000408828100003

    View details for PubMedID 28779487

  • The CogBIAS longitudinal study protocol: cognitive and genetic factors influencing psychological functioning in adolescence. BMC psychology Booth, C., Songco, A., Parsons, S., Heathcote, L., Vincent, J., Keers, R., Fox, E. 2017; 5 (1): 41

    Abstract

    Optimal psychological development is dependent upon a complex interplay between individual and situational factors. Investigating the development of these factors in adolescence will help to improve understanding of emotional vulnerability and resilience. The CogBIAS longitudinal study (CogBIAS-L-S) aims to combine cognitive and genetic approaches to investigate risk and protective factors associated with the development of mood and impulsivity-related outcomes in an adolescent sample.CogBIAS-L-S is a three-wave longitudinal study of typically developing adolescents conducted over 4 years, with data collection at age 12, 14 and 16. At each wave participants will undergo multiple assessments including a range of selective cognitive processing tasks (e.g. attention bias, interpretation bias, memory bias) and psychological self-report measures (e.g. anxiety, depression, resilience). Saliva samples will also be collected at the baseline assessment for genetic analyses. Multilevel statistical analyses will be performed to investigate the developmental trajectory of cognitive biases on psychological functioning, as well as the influence of genetic moderation on these relationships.CogBIAS-L-S represents the first longitudinal study to assess multiple cognitive biases across adolescent development and the largest study of its kind to collect genetic data. It therefore provides a unique opportunity to understand how genes and the environment influence the development and maintenance of cognitive biases and provide insight into risk and protective factors that may be key targets for intervention.

    View details for PubMedID 29284537

    View details for PubMedCentralID PMC5747087

  • Non-steroidal anti-inflammatory drugs (NSAIDs) for cancer-related pain in children and adolescents (Protocol) Cochrane Database of Systematic Reviews Cooper, T. E., Heathcote, L. C., Anderson, B., Gregoire, M., Eccleston, C. 2017; 2
  • Biased interpretations of ambiguous bodily threat information in adolescents with chronic pain Pain Heathcote, L. C., Jacobs, K., Eccleston, C., Fox, E., Lau, J. Y. 2017; 158 (3): 471-478
  • Pain and cancer survival: A cognitive-affective model of symptom appraisal and the uncertain threat of disease recurrence Pain Heathcote, L. C., Eccleston, C. 2017
  • Antiepileptic drugs for chronic non-cancer pain in children and adolescents (Protocol) Cochrane Database of Systematic Reviews Wiffen, P. J., Cooper, T. E., Heathcote, L. C., Clinch, J., Howards, R., Krane, E., Lord, S., Sethna, N., Schecter, N., Wood, C. 2017; 2
  • Child attention to pain and pain tolerance are dependent upon anxiety and attention control: An eye-tracking study European Journal of Pain Heathcote, L. C., Lau, J. Y., Mueller, S. C., Fox, E., Bosmans, M., Vervoort, T. 2017; 21 (2): 250-263

    View details for DOI 10.1002/ejp.920

  • Pain Neuroscience Education: State of the Art and Application in Pediatrics. Children (Basel, Switzerland) Robins, H., Perron, V., Heathcote, L. C., Simons, L. E. 2016; 3 (4)

    Abstract

    Chronic pain is a widespread problem in the field of pediatrics. Many interventions to ameliorate pain-related dysfunction have a biobehavioral focus. As treatments for chronic pain (e.g., increased movement) often stand in stark contrast to treatments for an acute injury (e.g., rest), providing a solid rationale for treatment is necessary to gain patient and parent buy-in. Most pain treatment interventions incorporate psychoeducation, or pain neuroscience education (PNE), as an essential component, and in some cases, as a stand-alone approach. The current topical review focuses on the state of pain neuroscience education and its application to pediatric chronic pain. As very little research has examined pain neuroscience education in pediatrics, we aim to describe this emerging area and catalyze further work on this important topic. As the present literature has generally focused on adults with chronic pain, pain neuroscience education merits further attention in the realm of pediatric pain in order to be tailored and implemented in this population.

    View details for DOI 10.3390/children3040043

    View details for PubMedID 28009822

    View details for PubMedCentralID PMC5184818

  • Negative Interpretation Bias and the Experience of Pain in Adolescents JOURNAL OF PAIN Heathcote, L. C., Koopmans, M., Eccleston, C., Fox, E., Jacobs, K., Wilkinson, N., Lau, J. Y. 2016; 17 (9): 972-981

    Abstract

    Negative interpretation bias, the tendency to appraise ambiguous situations in a negative or threatening way, has been suggested to be important for the development of adult chronic pain. To our knowledge, this is the first study to examine the role of a negative interpretation bias in adolescent pain. We first developed and piloted a novel task that measures the tendency for adolescents to interpret ambiguous situations as indicative of pain and bodily threat. Using this task in a separate community sample of adolescents (N = 115), we then found that adolescents who catastrophize about pain, as well as those who reported more pain issues in the preceding 3 months, were more likely to endorse negative interpretations, and less likely to endorse benign interpretations, of ambiguous situations. This interpretation pattern was not, however, specific for situations regarding pain and bodily threat, but generalized across social situations as well. We also found that a negative interpretation bias, specifically in ambiguous situations that could indicate pain and bodily threat, mediated the association between pain catastrophizing and recent pain experiences. Findings may support one potential cognitive mechanism explaining why adolescents who catastrophize about pain often report more pain.This article presents a new adolescent measure of interpretation bias. We found that the tendency to interpret ambiguous situations as indicative of pain and bodily threat may be one potential cognitive mechanism explaining why adolescents who catastrophize about pain report more pain, thus indicating a potential novel intervention target.

    View details for DOI 10.1016/j.jpain.2016.05.009

    View details for Web of Science ID 000382796000003

    View details for PubMedID 27263991

  • Pain neuroscience education: State of the art and application in pediatrics Children Robins, H., Perron, V., Heathcote, L. C., Simons, L. E. 2016; 3 (43)

    Abstract

    Chronic pain is a widespread problem in the field of pediatrics. Many interventions to ameliorate pain-related dysfunction have a biobehavioral focus. As treatments for chronic pain (e.g., increased movement) often stand in stark contrast to treatments for an acute injury (e.g., rest), providing a solid rationale for treatment is necessary to gain patient and parent buy-in. Most pain treatment interventions incorporate psychoeducation, or pain neuroscience education (PNE), as an essential component, and in some cases, as a stand-alone approach. The current topical review focuses on the state of pain neuroscience education and its application to pediatric chronic pain. As very little research has examined pain neuroscience education in pediatrics, we aim to describe this emerging area and catalyze further work on this important topic. As the present literature has generally focused on adults with chronic pain, pain neuroscience education merits further attention in the realm of pediatric pain in order to be tailored and implemented in this population.

    View details for DOI 10.3390/children3040043

    View details for PubMedCentralID PMC5184818

  • High trait anxiety during adolescence interferes with discriminatory context learning NEUROBIOLOGY OF LEARNING AND MEMORY Kadosh, K. C., Haddad, A. D., Heathcote, L. C., Murphy, R. A., Pine, D. S., Lau, J. Y. 2015; 123: 50-57

    Abstract

    Persistent adult anxiety disorders often begin in adolescence. As emphasis on early treatment grows, we need a better understanding of how adolescent anxiety develops. In the current study, we used a fear conditioning paradigm to identify disruptions in cue and context threat-learning in 19 high anxious (HA) and 24 low anxious (LA) adolescents (12-17years). We presented three neutral female faces (conditioned stimulus, CS) in three contingent relations with an unconditioned stimulus (UCS, a shrieking female scream) in three virtual room contexts. The degree of contingency between the CSs and the UCSs varied across the rooms: in the predictable scream condition, the scream followed the face on 100% of trials; in the unpredictable scream condition, the scream and face appeared randomly and independently of each other; in the no-scream condition the CS was presented in the absence of any UCS. We found that the LA adolescents showed higher levels of fear-potentiated startle to the faces relative to the rooms. This difference was independent of the contingency condition. The HA adolescents showed non-differential startle between the CSs, but, in contrast to previous adult data, across both cue types displayed lowest startle to the unpredictable condition and highest startle to the no-scream condition. Our study is the first to examine context conditioning in adolescents, and our results suggest that high trait anxiety early in development may be associated with an inability to disambiguate the signalling roles of cues and contexts, and a mislabelling of safety or ambiguous signals.

    View details for DOI 10.1016/j.nlm.2015.05.002

    View details for Web of Science ID 000359510900007

    View details for PubMedID 25982943

  • The puzzle of attentional bias to pain: beyond attention PAIN Crombez, G., Heathcote, L. C., Fox, E. 2015; 156 (9): 1581-1582
  • The relationship between adolescents' pain catastrophizing and attention bias to pain faces is moderated by attention control PAIN Heathcote, L. C., Vervoort, T., Eccleston, C., Fox, E., Jacobs, K., Van Ryckeghem, D. M., Lau, J. Y. 2015; 156 (7): 1334-1341

    Abstract

    This study considered the attentional functioning of adolescents with varying levels of pain catastrophizing. Specifically, we investigated the relationship between pain catastrophizing and attention bias to pain facial expressions. Furthermore, drawing on dual process models in the context of pain, we investigated the moderating role of attention control on this relationship. Adolescents (N = 73; age, 16-18 years) performed a dot-probe task in which facial expressions of pain and neutral expressions were presented for 100 milliseconds and 1250 milliseconds. Participants also completed self-report pain catastrophizing and attention control measures. We found that although there was no main effect of pain catastrophizing on attention bias towards pain faces, attention control did significantly moderate this relationship. Further analysis revealed that lower levels of attention control were significantly associated with increasing attentional vigilance towards pain faces only within high catastrophizing adolescents. In addition, we found that poorer attention control was related to increased attention bias for pain faces (regardless of pain catastrophizing level) when these faces were presented for relatively longer durations (ie, 1250 milliseconds) but not for short durations (ie, 100 milliseconds). This study supports a dual process model of attentional processes in pain, thus replicating previous findings within the psychopathology literature but extending them to the study of pain. Theoretical and clinical implications of our findings are discussed.

    View details for DOI 10.1097/j.pain.0000000000000174

    View details for Web of Science ID 000357426200020

    View details for PubMedID 25830926

  • Systematic Review and Meta-Analysis of Psychological Therapies for Children With Chronic Pain JOURNAL OF PEDIATRIC PSYCHOLOGY Fisher, E., Heathcote, L., Palermo, T. M., Williams, A. C., Lau, J., Eccleston, C. 2014; 39 (8): 763-782

    Abstract

    This systematic review and meta-analysis examined the effects of psychological therapies for management of chronic pain in children.?Randomized controlled trials of psychological interventions treating children (<18 years) with chronic pain conditions including headache, abdominal, musculoskeletal, or neuropathic pain were searched for. Pain symptoms, disability, depression, anxiety, and sleep outcomes were extracted. Risk of bias was assessed and quality of the evidence was rated using GRADE.?35 included studies revealed that across all chronic pain conditions, psychological interventions reduced pain symptoms and disability posttreatment. Individual pain conditions were analyzed separately. Sleep outcomes were not reported in any trials. Optimal dose of treatment was explored. For headache pain, higher treatment dose led to greater reductions in pain. No effect of dosage was found for other chronic pain conditions.?Evidence for psychological therapies treating chronic pain is promising. Recommendations for clinical practice and research are presented.

    View details for DOI 10.1093/jpepsy/jsu008

    View details for Web of Science ID 000343398100002

    View details for PubMedID 24602890

  • Age-related changes in attentional control across adolescence: how does this impact emotion regulation capacities? Frontiers in psychology Cohen Kadosh, K., Heathcote, L. C., Lau, J. Y. 2014; 5: 111-?

    Abstract

    This study set out to establish the novel use of the go/no-go Overlap task for investigating the role of attentional control capacities in the processing of emotional expressions across different age-groups within adolescence: at the onset of adolescence (11-12 year-olds) and toward the end of adolescence (17-18 year-olds). We also looked at how attentional control in the processing of fearful, happy, and neutral expressions relates to individual differences in trait anxiety in these adolescent groups. We were able to show that younger adolescents, but not older adolescents had more difficulties with attention control in the presence of all faces, but particularly in the presence of fearful faces. Moreover, we found that across all groups, adolescents with higher trait anxiety exhibited attentional avoidance of all faces, which facilitated relatively better performance on the primary task. These differences in reaction time emerged in the context of comparable accuracy level in the primary task across age-groups. Our results contribute to our understanding of how attentional control abilities to faces but in particular fearful expressions may mature across adolescence. This may affect learning about the environment and the acquisition of behavioral response patterns in the social world.

    View details for DOI 10.3389/fpsyg.2014.00111

    View details for PubMedID 24575077

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