Appendix 2: Literature review of paediatric chronic pain

Harrison LE, Pate JW, Richardson PA, Ickmans K, Wicksell RK, Simons LE. Bestevidence for the rehabilitation of chronic pain part 1: Paediatric pain. Journal of clinical medicine. 2019 Sep;8(9):1267. Overview

Rehab for chronic pain applies the biopsychosocial model which accounts for factors that contribute to and maintain pain symptoms and related disability: Biological Psychological Social Environmental

Requires a comprehensive and multidisciplinary approach –psychological, physical, and occupational

Interventions based in realm of rehab and typically delivered by an MDT (including medicine, nursing, psychology, PT and/or OT) Emphasis on functional improvements in presence of pain (rather than immediate analgesia as with acute pain)

Monodisciplinary rehabilitation treatments have been found to be inferior to multidisciplinary and interdisciplinary treatment approaches, where physical and occupation therapy are combined with psychological intervention

Unique to paediatric rehabilitative approaches is the emphasis on including parents to optimize treatment outcomes

Rehabilitative Inpatient Outpatient – adherence can be suboptimal – highlights importance of thorough assessment and delivery of tailored services that best meet need of child and family Explanation of differences of acute vs chronic pain Emphasis of the non-protective nature of chronic pain Changes conceptual understanding of pain and principles that guide biopsychosocial approach prepares children for biopsychosocial treatments Commonly MDT approach, can utilise free online resources and complement an individually tailored approach delivered by therapist Evidence in adults suggesting pain education improves outcomes, but paediatric research is more scarce Self-regulation of physiological responses to pain (e.g., HR, breathing rate, skin temperature and muscle tension) Psychoeducation Relaxation training Mindfulness based stress reduction Some evidence for role of yoga and massage Identifying and addressing negative cognitions Acceptance and value bases exercises (including ACT) Behavioural exposures Aim to improve functioning by reducing avoidance Parent coaching Important role in managing pain and maintaining or improving function Reducing parent distress and shifting to an encouraging function Physical and occupational therapies Focus on improving physical functioning Engaging in avoided activities Self-management approach

Goals of improving Strength Flexibility Endurance Joint stability Tolerance for weight-bearing Coordination Balance Proprioception

Promote independence and return to functioning → active interventions have more significant role than passive interventions (e.g., massage, TENS)

Movement in presence of pain

OT: Maximising age appropriate activities of daily living, self-care, academic and family activities

Desensitisation Sleep hygiene, CBT Psychological conditions that may be a contributing factor and an outcome to chronic pain condition RCT comparing Fibromyalgia integrative training vs traditional CBT demonstrated significant improvements in disability and greater decreases in pain intensity compared to CBT only To be considered an IIPT must include 3 or more disciplines housed within the same facility who work in an integrated manner to provide treatment day hospital or an inpatient setting typically require patient to participate in exercise-based therapies (PT and OT) as well as psychological interventions for total 8 hours/day

studies indicate decrease in anxiety, pain catastrophising, disability and improvements in school attendance improvements in pain severity and physical and psychological functioning

IIPT programs share the primary goal of improved functioning across domains

Variability in terms of: Structure Organisation Frequency of treatment across disciplines

Distinction is in outpatient vs inpatient models Functional improvements in both Several programs offer both inpatient and outpatient –triaged to level of care based on individual need

Length of stay Flexible based on patient need Fixed 3 week One day workshops Group based psychological interventions Benefit of shared experience, social support E.g., ‘The Comfort Ability’ Delivered to children and parents CBT based Development of plan to support functional improvement

Internet and mobile applications Address access barriers for paediatric pain management services

WebMAP – 8 week online psychological intervention for children & parents Other technology – symptom self-monitoring, intervention delivery involving goal setting, improving functioning, coping skills training & practise Social support – discussion boards, goal sharing, group based challenges Digital based ACT – moderate to large effects in primary and secondary outcomes Review found remotely delivered psychological therapies were beneficial at reducing pain intensity across pain groups Allow access for patients Remotely delivered interventions may not be appropriate for all patients –more complex patients would likely benefit from more intensive treatments

Augmented and virtual reality Found to be effective tool for reducing pain sensations in patients with acute pain

Pain education Psychological interventions Physiological and rehabilitative interventions Addressing comorbidities & optimising outcomes Interdisciplinary Outpatient Pain Treatment Intensive interdisciplinary pain treatment (IIPT) Emerging Pain Treatment Intervention Formats

Overview Pain education Psychological interventions Physiological and rehabilitative interventions Addressing comorbidities & optimising outcomes Interdisciplinary Outpatient Pain Treatment Intensive interdisciplinary pain treatment (IIPT) Emerging Pain Treatment Intervention Formats

Comprehensive multidisciplinary and interdisciplinary treatment based on behavioural medicine approaches are needed for children and adolescents with persistent pain. Pain Science Education is commonly implemented with several resources currently available, yet evidence for its use is scarce. Unique to paediatric rehabilitative approaches is the emphasis on including parents to optimize treatment outcomes. Innovative pain treatment intervention formats such as mobile applications and virtual reality enhance the delivery and reach of evidence-based tools. Comprehensive multidisciplinary/interdisciplina ry treatment based on contemporary understanding of pain (neuro) science are needed for children and adolescents with persistent pain. Continued research on effectiveness of VR within pain rehabilitation is needed

Guidelines on the Management of Chronic Pain in Children – WHO 2020

Capacity strengthening Education and training Assessment of pain Symptoms and treatment responses Assessment tools Treatment modalities Screening for and treatment of adverse effects of interventions Communication and support strategies for children and their families Psychological interventions When psychological therapies were examined as a group, they provided: Small benefits compared to any control for the outcomes of reducing pain intensity 50% pain reduction (very low certainty) and functional disability Global judgement of satisfaction post-treatment and at follow-up Patient global impression of change was also improved post treatment and at followup

No beneficial effects were demonstrated for the outcomes of: 30% pain reduction Heath-related quality of life Physical interventions When compared to standard care or an active control PT had beneficial effects on: pain intensity and functional disability immediately posttreatment no benefits were noted at longer term follow-up for these outcomes

No difference found between treatment and control post treatment or follow-up for: Health related quality of life Role-functioning Emotional functioning (depression or anxiety)

Activity participation and patient global impression of change improved posttreatment in the treatment group Optimising interventions Appropriate communication/education on biopsychosocial nature of pain Collaborative goal establishment Social and educational support Community or home based support for children and families Care pathways that revolve around child and families schedule and educational timetable Care to avoid disruption to child’s routine physical and social environments Attention to maintenance and sustainability of intervention and long-term outcomes Continually seeking approaches which sustain and augment care and positive outcomes

Overview Pain education Psychological interventions Physiological and rehabilitative interventions Addressing comorbidities & optimising outcomes Interdisciplinary Outpatient Pain Treatment Intensive interdisciplinary pain treatment (IIPT) Emerging Pain Treatment Intervention Formats

Hechler T, Kanstrup M, Holley AL, Simons LE, Wicksell R, Hirschfeld G, Zernikow B. Systematic review on intensive interdisciplinary pain treatment of children with chronic pain. Paediatrics. 2015 Jul 1;136(1):115-27.

One randomized controlled trial and 9 nonrandomized treatment studies were identified and a meta-analysis was conducted separately on: pain intensity, disability, and depressive symptoms revealing positive treatment effects. At posttreatment, there were large improvements for disability, and small to moderate improvements for pain intensity and depressive symptoms. The positive effects were maintained at short-term follow-up. Findings demonstrated extreme heterogeneity. More than half of the treatments included 5 disciplines (7 studies). Most frequently, the treatments included medical (9 studies), psychological (10 studies), and physical interventions (10 studies). Mean treatment duration was 16 days (SD 5.3; range: 5–27 days).

Effects in nonrandomized treatment studies cannot be attributed to IIPT alone. Because of substantial heterogeneity in measures for school functioning and anxiety, meta-analyses could not be computed. There is preliminary evidence for positive treatment effects of IIPT, but the small number of studies and their methodological weaknesses

Emotional functioning (both depression and anxiety) Role functioning and sleepquality post treatment and at follow-up

Face-to-face vs remote (internet, smartphone, CDROM or manuals) for CBT, ACT, behavioural or relaxation therapies Face-to-face reduced: Pain intensity post treatment Pain by 50% or more post treatment and at follow-up Disability post treatment and at follow-up Increased activity participation post treatment and satisfaction at follow-up

Remote therapies Reduced pain intensity post treatment Had beneficial effects on 50% pain reduction, satisfaction, and impression of change post treatment and at follow-up

No benefits were reported for other outcomes These studies of PT interventions included few participants and had serious limitations (risk of bias) in study design and execution. The body of evidence for all outcomes was therefore assessed as very low certainty, both immediately postintervention and at longerterm follow-up

Pharmacological interventions Minimal studies for each drug class Included RCTs were small and may not have had sufficient power to detect statistically significant differences in the incidence of less common adverse events Reassessing disease status Pain control using validated tools appropriate to child’s age developmental status mode of communication culture Use of ‘booster sessions’ for effective interventions can be used to enhance outcomes over the long term

As children age care teams must ensure that appropriately tailored services evolve to meet the child’s need in terms of: Capabilities Decision-making capacity Views Interests Activities

Facilitation of a smooth transition from child to adult services for adolescents

Overview Pain education Psychological interventions Physiological and rehabilitative interventions Addressing comorbidities & optimising outcomes Interdisciplinary Outpatient Pain Treatment Intensive interdisciplinary pain treatment (IIPT) Emerging Pain Treatment Intervention Formats

Agoston AM, Sieberg CB. Nonpharmacologic treatment of pain. In Seminars in paediatric neurology 2016 Aug 1 (Vol. 23, No. 3, pp. 220-223). WB Saunders.

Systematic reviews and metaanalyses of randomized controlled trials of psychological interventions have demonstrated evidence for psychological approaches intreating procedural pain and multiple types of chronic pain, including headaches, abdominal pain, and musculoskeletal pain. Preparation and psychoeducation preparation for procedural pain – research to support efficacy of effects and psychoeducation in reducing procedural pain CBT Brief, goal oriented psychotherapy Commonly researched and supported for management of paediatric pain Combination of cognitive and behavioural techniques that involve a variety of cognitive skills and behavioural strategies

Specific CBT techniques for paediatric pain CBT framework used to teach children strategies to identify and restructure maladaptive pain related thoughts and address behaviours that might contribute to pain related disability Goals include: directing attention away from pain enhancing sense of control over pain diminishing negative thoughts related to pain that may contribute to emotional distress

modify pain sensations, promote self-control and selfmanagement, increase functioning, and reduce maladaptive behavioural responses to pain

Distraction Exercise and alternative approaches Exercise through PT and OT are key components of MDT approach Yoga, acupuncture, massage, tactile desensitisation, progressive weight bearing, transcutaneous electrical nerve stimulation MDT approaches Strong support for multicomponent CBT approaches for acute and chronic pain Multidisciplinary treatment approaches including Pharmacological Physical or OT Psychological

suggest a need for more research on IIPTs for children.

Results need to be interpreted with caution because of the lack of RCTs and the study weaknesses of the NRSs. However, they suggest that the collaborative treatment goal to improve functioning despite ongoing pain may be achieved immediately in children and maintained at short-term follow-up. This is important given that the affected children suffer for an average of 3 years before initiating IIPT.

Overview Pain education Psychological interventions Physiological and rehabilitative interventions Addressing comorbidities & optimising outcomes Interdisciplinary Outpatient Pain Treatment Intensive interdisciplinary pain treatment (IIPT) Emerging Pain Treatment Intervention Formats

Liossi C, Johnstone L, Lilley S, Caes L, Williams G, Schoth DE. Effectiveness of interdisciplinary interventions in paediatric chronic pain management: a systematic review and subset meta-analysis. British journal of anaesthesia. 2019 Aug 1;123(2):e359-71

Review of the effectiveness of interdisciplinary interventions in the management of paediatric chronic pain. Patients randomised to interdisciplinary interventions reported significantly lower pain intensity 0-1 month postintervention compared with patients randomised to the control groups. Within-groups analysis of patients receiving interdisciplinary interventions showed significant improvements pre- to postintervention in pain intensity, functional disability, anxiety, Conclusions: Overall, interdisciplinary interventions show promise in providing a range of clinical benefits for children with chronic pain. Methodologically robust randomised controlled trials using standardised outcome measures are needed, however, to guide clinical care.

Significant reductions were found in pain intensity preintervention to immediate post-intervention, and at 3 and 12 month follow-up points. Significant improvements were also found in functional disability pre-intervention to

For both procedural and chronic pain

Exposure and psychological desensitisation Systemic habituation → decreased anxiety and fear Reduction in avoidance behaviour

Relaxation techniques Diaphragmatic breathing Progressive muscle relaxation Self-imagery, guided imagery

Acceptance and commitment therapy for chronic pain (ACT) ACT incorporates elements of CBT with focus on acceptance and mindfulness strategies Focus is not symptom control but rather reducing distress associated with pain Support in effectiveness in terms of self-reported functioning and quality of life

Use of technology Biofeedback – awareness and control through receiving feedback from physiological processes e.g., respiration, heart-rate variability, peripheral skin temperature Development of online CBT resources

Overview Pain education Psychological interventions Physiological and rehabilitative interventions Addressing comorbidities & optimising outcomes Interdisciplinary Outpatient Pain Treatment Intensive interdisciplinary pain treatment (IIPT) Emerging Pain Treatment Intervention Formats

depression, catastrophising, school attendance, school functioning, and pain acceptance. Few differences were found between interventions delivered in inpatient vs outpatient settings. Significant heterogeneity due mainly to differing outcome variables and intervention content was found in most analyses.

PCP Paediatric chronic pain (PCP) is defined as persistent or recurring pain of any aetiology lasting longer than 3 months. Liossi and Howard recently summarised the evidence that suggests a purely biological model of PCP is outdated and incorrect and provided a roadmap for its biopsychosocial assessment and formulation, and subsequent multimodal, interdisciplinary management. Interdisciplinary interventions varied in their content, number of sessions, and follow-up time-points, although all were co-ordinated by two or more healthcare professionals of different disciplines Fifteen interventions were conducted in an outpatient setting, and 13 studies in an inpatient setting. Sixteen studies clearly reported significant reductions in pain intensity by patients receiving interdisciplinary interventions pre-to post-intervention.

The aim of this review was to examine the effectiveness of interdisciplinary interventions for the management of PCP. Between-groups analyses revealed significantly lower pain intensity 0-1 month postintervention in patients receiving interdisciplinary interventions compared with those in the control group. immediate post-intervention and 3 month follow-up, anxiety preintervention to immediate post-intervention, 3 and 12 month follow-up points, depression pre-intervention to immediate post-intervention and 1 month follow-up, catastrophising preintervention to immediate post-intervention and 3 month follow-up, school attendance and school functioning preintervention to 3 month follow-up, and pain acceptance preintervention to immediate post-intervention.

Significant heterogeneity was found in most analyses, however. Although the pattern of results remained the same in subsequent sensitivity analyses (except for school attendance which was no longer significant), heterogeneity also remained high in most instances.

Overall, the results of the prepost analyses agree with those of Hechler and colleagues’ former review, which reported significant reductions in pain intensity, disability, and depression from pre-treatment to immediate post-treatment and short-term follow-up (2e6 months). We also agree with this former review in advising caution in the interpretation of results, however, because of high levels of heterogeneity observed in most analyses.

Overview Pain education

Miró J, McGrath PJ, Finley GA, Walco GA. Paediatric chronic pain programs: current and ideal practice. Pain reports. 2017 Sep;2(5).

A web-based international survey was used to collect information. The survey contained 86 questions seeking respondent professional demographic data and information about the pain program with which the respondent was affiliated at the time (program organization, types of pain problem treated, professionals involved, services provided, size of the program, research, professional training, public education and advocacy, and funding sources).

Respondents were 136 paediatric pain experts representing different specialties located in 12 countries. Most respondents indicated that ideal programs would have a multidisciplinary staff; provide a wide range of treatments for different chronic pain problems; integrate research, formal clinical training of specialists, and public education and advocacy into their activities; and be an accredited part of the public health system.

The results of this survey show that most current chronic pain treatment programs function as outpatient services, multidisciplinary in nature, are based on a biopsychosocial model of pain, and provide cognitive behavioural therapy–based psychological treatments. These programs highlight research with training and education of future professionals and advocacy being integral parts.

The results of this study also show that not all programs are staffed with the professionals required for multidisciplinary pain centres, according to IASP recommendations, which

Psychological interventions Physiological and rehabilitative interventions Addressing comorbidities & optimising outcomes Interdisciplinary Outpatient Pain Treatment Intensive interdisciplinary pain treatment (IIPT) Emerging Pain Treatment Intervention Formats

Overview Pain education Psychological interventions Physiological and rehabilitative interventions Addressing comorbidities & optimising outcomes Interdisciplinary Outpatient Pain Treatment Intensive interdisciplinary pain treatment (IIPT) Emerging Pain Treatment Intervention Formats

Simons LE, Basch MC. State of the art in biobehavioural approaches to the management of chronic pain in childhood. Pain management. 2016 Jan;6(1):49-61.

include physicians, nurses, physical therapists, and psychologists. Thus, although current paediatric chronic pain programs provide a range of focal treatments, they need a wider variety of professionals, if they are to provide the best treatment possible.

The evolving standard of care for paediatric chronic pain involves a multi- and often inter-disciplinary treatment team.

Options for biobehavioural treatment are expanding to be both face-to-face and remotely accessible, with increasing precision in targeting known psychosocial risk factors that impact recovery. Screening tools that stratify patients by psychosocial risk have the potential to be easily implemented in a busy clinic setting, arming providers with key clinical information to guide treatment decisionmaking. Explanation of chronic pain, nonprotective nature of persistent pain signals and processing Explanation of theories behind focus of treatment Self-regulation of physiology –e.g., relaxation training, biofeedback, hypnosis Self-regulation of HR, skin temp, muscle tension (biofeedback) Progressive relaxation –diaphragmatic breathing, guided imagery

Cognitive techniques –cognitive reframing, cognitive diffusion

Behavioural exposure Parent involvement Teaching operant techniques to guide parents in responding to, managing, and coping with child’s pain Emotional distress in parents Reinforcement of positive coping, reward systems, communication and modelling positive coping

An emerging approach to better match patient to treatment involves using screening tools to stratify patients by risk of poor clinical out-come, such as the Keele STarT Back Screening Tool (SBST) and the paediatric adaptation of this tool, the Paediatric Pain Screening Tool (PPST). Allocation to the highrisk group for both of these tools is driven by the tools’ psychosocial variables.

Implementation of a stratified treatment approach among youth with chronic pain is still needed. Additionally, increasing our understanding of the patient phenotype to include any potential sensory abnormalities assessed via quantitative sensory testing can potentially enhance the accuracy of treatments recommended. Meta-analysis found multidisciplinary outpatient pain management clinical displayed superiority to no treatment, waiting-list and singlediscipline interventions (e.g., sole pharmacology or physical therapy).

Flor and colleagues’ results indicated that along with reductions in pain, patients receiving multidisciplinary treatment reported increases in mood and decreases in disability and healthcare utilization at both the end of treatment and follow-up time points. Similar positive results have been observed in paediatric multidisciplinary outpatient pain clinics with patients reporting significantly fewer doctor visits and decreased pain, somatic complaints, and functional disability 3 months after their initial pain clinic evaluation

Adherence to treatment recommendations in a paediatric multidisciplinary outpatient pain clinic is often suboptimal.

Specifically, almost a third of patients failed to initiate recommended changes in medication, slightly fewer never began new recommended physical therapy interventions, and approximately half of patients did not enter recommended CBT. 38 Nationwide paediatric chronic pain programs in the USA. Inpatient Outpatient Day hospital treatment

For patients who continue to struggle with their pain symptoms and have difficulty engaging in recommended treatments, more intensive treatment approaches may be warranted. After participation in a 3-week intensive program encompassing multidisciplinary treatment domains, a sample of 57 adolescents with chronic pain and their parents reported significant physical improvements at the end of treatment and 3-month followup. Additional improvements in anxiety and somatic symptoms were reported at 3month follow-up. Parents reported significant improvements in their symptoms of anxiety, depression and stress posttreatment and these changes were maintained at 3-month follow-up.

A recent systematic review and meta-analysis performed by Hechler and col-leagues demonstrated preliminary evidence for positive effects of intensive interdisciplinary pain treatment. Overall, patients showed improvements in the domains of disability, pain intensity and depressive symptoms at post-treatment and short-term follow-up Group-based CBT Promotes peer-support, reduces feelings of isolation and feeling misunderstood Benefits can extend to parents

Internet-based CBT Benefits in reducing access barriers Self-paced nature and lower risk of stigma Limitations of equity of access to technology and response to individual needs Effect sizes for internetdelivered CBT for pain were promising but below those found for internet delivered CBT for anxiety and depression for children

Example of web-based family CBT to adolescents with chronic pain (Palermo & colleagues) Adolescents receive pain education, relaxation training, and other CBT skills Parents receive training on reinforcement of positive coping, reward systems communication Reduction in pain and activity limitations post-treatment compared with waitlist control group, gains maintained at a 3-month follow-up