Mapping the evidence and gaps of interventions for pediatric chronic pain to inform policy, research, and practice: A systematic review and quality assessment of systematic reviews

Figures & data

Figure 1. PRISMA review flowchart

Table 1. Characteristics of included reviews

Author, year	Aim	Meta-analysis	Search date	No. and type of relevant studies	Age and chronic pain population(s)	Setting(s)	Type of intervention(s)	AMSTAR-2 quality rating
Abbott et al., 2017^Citation39	To determine the effectiveness of psychosocial interventions for reducing pain in school-aged children with recurrent abdominal pain	Yes*	06/2017	18 RCTs	6–18 years Recurrent abdominal pain, functional abdominal pain, IBS	Gastroenterology and pain outpatient clinic, community	Psychological	High
Abujaradeh et al., 2018^Citation41	To determine the benefits/efficacy of mindfulness-based interventions implemented among adolescents with chronic diseases in clinical settings	No	11/2017	8 RCTs and NRS	12–18 years Mixed chronic pain	Tertiary care multidisciplinary pain clinic or hospital setting	Psychological	Low
American Academy of Pediatrics, 2005^Citation34 and Di Lorenzo et al., 2005^Citation35	To examine the diagnostic and therapeutic value of a medical and psychologic history, diagnostic tests, and pharmacological and behavioral therapy for chronic abdominal pain	No + CPG	??/2002	8 RCTs and NRS	5–17 years Abdominal pain	??	Psychological Pharmacological Other	Low
Anie and Green, 2015^Citation74	To examine the evidence that psychological interventions improve the ability of people with sickle cell disease to cope with their condition	Yes*	02/2015	4 RCTs	6–18 years+ Sickle cell disease	“Urban setting”	Psychological	Moderate
Arruda et al., 2018^Citation62	To review the comorbidities and treatment of chronic migraine in children and adolescents in the last ten years, summarizing evidence-based recommendations for disease management	No	??/2017	4 RCTs and NRS	7–17 years Headaches, migraine	Inpatient, outpatient headache clinics	Pharmacological Interdisciplinary	Critically low
Badawy et al., 2018^Citation75	To (1) review the types of technological tools used for self-management of sickle cell disease, (2) discover and describe what self-management activities these tools were used for, and (3) assess the efficacy of these technologies in self-management	No	11/2016	5 RCTs and NRS	13–18 years+ Sickle cell disease	e-Health	Psychological Interdisciplinary	Low
Bailey and McManus, 2008^Citation63	To evaluate which treatment could be effective in the emergency department for children with migraine and status migrainous	No	06/2007	14 RCTs	4–18 years Migraines	Emergency department, outpatient neurology clinics	Pharmacological	Critically low
Barnes, 2015^Citation64	To examine treatments for acute attacks and the effects of pharmacological prophylaxis for migraine headache in children	No	06/2014	23 RCTs and reviews of RCTs	3–18 years Migraines, headaches	??	Pharmacological	Moderate
Bredlau et al., 2013^Citation71	To review the use of ketamine in the treatment of cancer-related pain in adults and children	No	02/2013	5 NRS	4–19 years Cancer pain	??	Pharmacological	Low
Brent et al., 2009^Citation59	To evaluate behavioral and psychological treatments applied to pediatric functional gastrointestinal disorders	No	??/2007	12 RCTs and NRS	4–18 years Recurrent abdominal pain, IBS, functional abdominal pain, functional dyspepsia, stomachache, stomach pain	Outpatient, community	Psychological Other Interdisciplinary	Critically low
Cairns et al., 2018^Citation76	To evaluate interventions for patellar tendon–related pain in children and adolescents	No	11/2017	3 RCTs and NRS	10–18 years Patellar tendon pain, Osgood-Schlatter’s	University physical therapy, secondary care orthopedics, orthopedic surgery department	Physical Pharmacological Interdisciplinary	Moderate
Cohen et al., 2017^Citation67	To assess the effects of psychosocial therapies on pain and function in children with rheumatic diseases	No	09/2015	5 RCTs and NRS	5–18 years Juvenile fibromyalgia, juvenile arthritis	??	Psychological	Low
Cooper, Wiffen, et al., 2017^Citation42	To assess the analgesic efficacy of antiepileptic drugs used to treat chronic non-cancer pain in children and adolescents	Yes*	09/2016	2 RCTs	7–18 years Fibromyalgia, CRPS-I or neuropathic pain	Tertiary care centers	Pharmacological	High
Cooper, Heathcote, et al, 2017^Citation72	To assess the analgesic efficacy of nonsteroidal anti-inflammatory drugs used to treat cancer-related pain in children and adolescents	Yes*	02/2017	0 RCTs	<18 years Cancer-related pain		Pharmacological	High
Cooper, Fisher, et al., 2017^Citation8	To assess the analgesic efficacy of opioids used to treat chronic non-cancer pain in children and adolescents	Yes*	09/2016	0 RCTs	<18 years Chronic non-cancer pain		Pharmacological	High
Eccleston et al., 2015^Citation43	To evaluate the efficacy of psychological therapies that include parents of children and adolescents with chronic illnesses	Yes*	07/2014	14 RCTs	<19 years Headache, sickle cell, recurrent abdominal pain, IBS, fibromyalgia, arthritis, mixed pain conditions	Outpatient clinics, community	Psychological	High
Eccleston et al., 2017^Citation44	To assess the analgesic efficacy of nonsteroidal anti-inflammatory drugs used to treat chronic non-cancer pain in children and adolescents	Yes*	09/2016	7 RCTs	2–18 years Chronic non-cancer pain	Pediatric rheumatology tertiary care units, pediatric centers, clinical centers	Pharmacological	High
Egunsola et al., 2019^Citation45	To examine the efficacy and safety of gabapentin and pregabalin for pain in children and adolescents	No	11/2017	2 RCTs	7–18 years CRPS, neuropathic pain, fibromyalgia	??	Pharmacological	High
Fellas et al., 2017^Citation70	To review the evidence for physical and mechanical interventions for lower-limb problems in juvenile idiopathic arthritis	Yes	06/2015	2 RCTs	5–19 years Juvenile idiopathic arthritis	Hospitals, pediatric rheumatology clinics	Physical	High
Ferro and Speechley, 2008^Citation68	To review of the prevalence of complementary and alternative medicine use in juvenile idiopathic arthritis, determinants of use, and outcomes associated with various therapies	No	10/2008	3 RCTs and NRS	“Children” Juvenile idiopathic arthritis	??	Psychological Other	Critically low
Fisher et al., 2018^Citation46	To determine any effect of psychological therapy for chronic and recurrent pain in children and adolescents	Yes*	05/2018	47 RCTs	6–18 years Mixed chronic pain, headaches, abdominal pain, IBS, inflammatory bowel disease, fibromyalgia, temporomandibular disorders, sickle cell disease	Hospitals, outpatient clinics, patient home	Psychological	High
Fisher et al., 2019^Citation47	To determine the efficacy of psychological therapies delivered remotely for the management of chronic pain in children and adolescents	Yes*	05/2018	10 RCTs	7–17 years Headache, juvenile idiopathic arthritis, abdominal pain, musculoskeletal, sickle cell disease	Via technology at home (Internet, CD-ROM)	Psychological	High
Hechler et al., 2015^Citation48	To review studies the effects of pediatric intensive interdisciplinary pain treatment	Yes	02/2014	10 RCTs and NRS	8–22 years Mixed (CRPS, headache, neuropathic, idiopathic, fibromyalgia/diffuse, disease-related, back, abdominal, pelvic, musculoskeletal, etc.)	Inpatient, day hospital setting, rehabilitation	Interdisciplinary	Moderate
Horvath et al., 2012^Citation60	To evaluate the effect of dietary fibers for treating abdominal pain-related functional gastrointestinal disorders in children	No	12/2011	3 RCTs	3–16 years Abdominal pain	Hospitals, community clinics	Other	Low
Huertas-Ceballos 2008^Citation77^,	To determine the effectiveness of medication for recurrent abdominal pain in school-age children	Yes*	12/2006	3 RCTs	5–18 years Abdominal migraine, recurrent abdominal pain, dyspepsia, IBS	??	Pharmacological Other	High
Huertas-Ceballos 2008^Citation78	To determine the effectiveness of psychosocial interventions for recurrent abdominal pain or IBS in school-age children	Yes*	12/2006	6 RCTs	5–18 years Recurrent abdominal pain	Community, outpatient clinic	Psychological Other Interdisciplinary	High
Kichline and Cushing, 2019^Citation49	To evaluate the effect of exercise on pediatric chronic pain	Yes	12/2016	11 RCTs and NRS	6–16 years Arthritis, fibromyalgia, low back pain, cancer, mixed	??	Physical	Low
Liossi et al., 2019^Citation50	To review the effectiveness of interdisciplinary interventions in the management of pediatric chronic pain	Yes	03/2018	28 RCTs and NRS	6–21 years Mixed (headache, abdominal pain, back, migraines, CRPS, pelvic, neuropathic, widespread/fibromyalgia, musculoskeletal), oncology (tumors, leukemia), arthritis	Inpatient, day treatment, outpatient	Interdisciplinary	High
Lonergan, 2016^Citation51	To examine the effectiveness of cognitive behavioral therapy in the treatment of chronic pain in children and adolescents	Yes	12/2014	9 RCTs	6–18 years Recurrent abdominal pain, fibromyalgia, headache or migraine	Outpatient, university, patient home	Psychological	Critically low
Martin et al., 2017^Citation40	To review the effectiveness of pharmacological interventions for recurrent abdominal pain in school-age children	Yes*	06/2016	16 RCTs	5–18 years Recurrent abdominal pain	Hospital pediatric outpatient clinics	Pharmacological	High
Michel et al., 2011^Citation52	To review relevant pediatric buprenorphine data, particularly in children suffering chronic pain	No	??	12 NRS	“Children” Oncology, postoperative		Pharmacological	Critically low
Newlove-Delgado et al., 2017^Citation10	To examine the effectiveness of dietary interventions in improving pain in school-age children with recurrent abdominal pain	Yes*	06/2016	19 RCTs	4–18 years Recurrent abdominal pain, functional gastrointestinal disorders, IBS	Pediatric gastroenterology clinics, primary care pediatric practices, community clinics	Other	High
Ng et al., 2017^Citation65	To review the efficacy of cognitive–behavioral therapy for pediatric migraine	Yes	05/2016	17 RCTs	7–18 years Migraine	Medical setting, school	Psychological	Critically low
Nijhof et al., 2018^Citation69	To review the evidence for nonpharmacological treatment for chronic musculoskeletal pain in pediatric rheumatic disease	No	10/2017	11 RCTs and NRS	5–18 years Juvenile idiopathic arthritis, systemic lupus erythematosus	??	Psychological Physical Interdisciplinary	Low
Ostojic et al., 2018^Citation80	To determine the efficacy of interventions for the management of pain in children and adolescents with cerebral palsy	No	04/2018	50 RCTs and NRS	<18 years Cerebral palsy (postoperative, hypertonia, cerebral palsy spastic hip disease)	Hospital, outpatient clinic	Physical Pharmacological Other Interdisciplinary	Low
Palermo et al., 2010^Citation53	To examine the efficacy of psychological interventions for pain and emotional and physical functioning in children	Yes	08/2008	18 RCTs	4–18 years Headache, migraine, abdominal pain, fibromyalgia	Hospital or clinic	Psychological	Moderate
Scheper et al., 2013^Citation81	To review state of the art of diagnostics and treatment of generalized joint hyper mobility and joint hyper mobility syndrome in children and young adults	No	??	3 RCTs	0–18 years Osteogenesis imperfecta, generalize joint hyper mobility, joint hyper mobility syndrome, Ehlers-Danlos	??	Physical Other	Moderate
Shah et al., 2016^Citation54	This review the role of interventional procedures in the treatment of chronic pain in children and adolescents	No	03/2013	133 NRS	“Children” Migraine, headache, neuropathic, postoperative, cystic fibrosis, sickle cell, juvenile idiopathic arthritis, head, abdomen, fibromyalgia, CRPS, phantom limb, back, chest, cancer	Inpatient, outpatient settings	Pharmacological	Critically low
Sprenger et al., 2011^Citation61	To examine the effectiveness of psychological therapies for children with recurrent abdominal pain	Yes	11/2009	10 NRS	4–18 years Recurrent abdominal pain	??	Psychological	Critically low
Tomé-Pires and Miró, 2012^Citation55	To review hypnotic treatments for chronic and cancer procedure-related pain in children	No	05/2010	2 RCTs	6–18 years Headache, abdominal pain	??	Psychological	Critically low
Trautmann et al., 2006^Citation66	To describe the state of evidence in the treatment of pediatric headaches	Yes	07/2004	23 RCTs	7–18 years Headache	Outpatient clinic, school	Psychological	Low
Velleman et al., 2010^Citation56	To review the use of computerized cognitive behavioral therapy with children and adolescents with pain	Yes	??/2008	4 RCTs	7–17 years Headaches, recurrent abdominal pain, musculoskeletal	Via computer in outpatient clinic, community	Psychological	Low
Weydert et al., 2003^Citation57	To review treatments for recurrent abdominal pain in children	No	??/2001	10 RCTs	3–18 years Recurrent abdominal pain, IBS, abdominal migraine	Primary and tertiary care, community	Psychological Pharmacological Other Interdisciplinary	Critically low
Wicksell et al., 2015^Citation58	To provide an overview of research on acceptance and commitment therapy for youths with physical concerns	No	??	8 RCTs and NRS	7–18 years Chronic pain	??	Psychological	Critically low
Wiffen et al., 2017^Citation73	To assess the analgesic efficacy, of opioids used to treat cancer-related pain in children and adolescents	Yes*	02/2017	0 RCTs	<18 years Cancer-related pain	—	Pharmacological	High
Yeung et al., 2017^Citation79	To review characteristics and management of endometriosis in adolescents	No	??	8 NRS	10–25 years Endometriosis	??	Other Interdisciplinary	Critically low
Zernikow et al., 2012^Citation37 and Häuser et al., 2012^Citation36	To provide a definition, diagnosis, and therapy of chronic widespread pain and so-called fibromyalgia syndrome in children and adolescents	No + CPG	12/2010	?? RCTs and NRS	“Children and adolescents” Chronic widespread pain, fibromyalgia	Inpatient, outpatient	Psychological Physical Pharmacological Interdisciplinary	Moderate

* = Cochrane review; RCT = randomized controlled trial; IBS = irritable bowel syndrome; NRS = nonrandomized study; CPG = clinical practice guideline; ?? = unclear/unknown; CRPS = complex regional pain syndrome; — = no studies.

Table 2. Interventions and outcomes of included reviews

			PedIMMPACT outcomes
Author, year	Intervention(s)	Longest follow-up time	Pain	Physical functioning	Emotional functioning	Role functioning	Quality of life	Sleep	Economic factors	Treatment satisfaction	Adverse events
Abbott et al., 2017^Citation39	CBT, hypnosis, written self-disclosure, yoga	>1 year	✔	✔	✔	✔	✔
Abujaradeh et al., 2018^Citation41	mindfulness-based interventions	6 months	✔	✔	✔	✔	✔
American Academy of Pediatrics, 2005^Citation34 and Di Lorenzo et al., 2005^Citation35	CBT, coping skills, famotidine, pizotifen, peppermint oil, fiber supplement, lactose-free diet, surgery	3 years	✔			✔				✔	✔
Anie and Green, 2015^Citation74	Education, various psychotherapies, art therapy	1 year	✔		✔	✔	✔		✔
Arruda et al., 2018^Citation62	Amitriptyline, corticoid infusion, peripheral nerve blocks. onabotulinumtoxina injections, pharmacological + CBT	1 year	✔	✔
Badawy et al., 2018^Citation75	Internet-delivered CBT, psychoeducation	7 months	✔	✔	✔			✔	✔	✔
Bailey and McManus, 2008^Citation63	Acetaminophen, ibuprofen, zolmitriptan, sumatriptan, rizatriptan, dihydroergotamine, ketorolac, prochlorperazine	24 hours	✔								✔
Barnes, 2015^Citation64	Almotriptan, ibuprofen, topiramate, flunarizine, sumatriptan, rizatriptan, zolmitriptan, eletriptan, propanolol, flunarizine	4 months	✔	✔							✔
Bredlau et al., 2013^Citation71	Ketamine	75 days	✔								✔
Brent et al., 2009^Citation59	Relaxation, hypnotherapy, CBT, psychoeducation, dietary (fiber), psychological + diet	1 year	✔	✔	✔	✔
Cairns et al., 2018^Citation76	Shockwave treatment + light activity, other physical exercises, local anesthetic, surgery + physical therapy	2–3 years	✔	✔							✔
Cohen et al., 2017^Citation67	CBT, coping skills, relaxation, education, distraction	4 months	✔	✔			✔				✔
Cooper, Wiffen, et al., 2017^Citation42	Antiepileptics (pregabalin, gabapentin)	15 weeks	✔	✔		✔	✔	✔		✔	✔
Cooper, Heathcote, et al., 2017^Citation72	NSAIDs	—	—	—	—		—	—	—	—	—
Cooper, Fisher, et al., 2017^Citation8	Opioids	—	—	—	—		—	—	—	—	—
Eccleston et al., 2015^Citation43	CBT, behavioral intervention	1 year	✔	✔	✔	✔	✔		✔	✔	✔
Eccleston et al., 2017^Citation44	NSAIDs	1 year	✔							✔	✔
Egunsola et al., 2019^Citation45	Antiepileptics (pregabalin, gabapentin)	15 weeks	✔					✔			✔
Fellas et al., 2017^Citation70	Foot orthotics, neoprene inserts	6 months	✔	✔			✔
Ferro and Speechley, 2008^Citation68	Relaxation, herbal therapy (Tripterygium wilfordii), massage therapy	6 months	✔	✔
Fisher et al., 2018^Citation46	CBT, relaxation with or without biofeedback, coping skills, problem-solving therapy, intensive inpatient rehabilitation	1 year	✔	✔	✔	✔	✔	✔	✔	✔	✔
Fisher et al., 2019^Citation47	CBT (CD-ROM, Internet)	1 year	✔	✔	✔	✔	✔	✔		✔	✔
Hechler et al., 2015^Citation48	Variations of combined pharmacological, psychological, physical	2 years	✔	✔	✔	✔
Horvath et al., 2012^Citation60	Dietary fiber	??	✔	✔		✔				✔	✔
Huertas-Ceballos 2008^Citation77	Pizotifen, famotidine, peppermint oil capsules	??	✔
Huertas-Ceballos 2008^Citation78	CBT, family therapy, dietary fiber, psychological + fiber	1 year	✔	✔		✔	✔			✔
Kichline and Cushing, 2019^Citation49	Aerobic exercise	6 months	✔
Liossi et al., 2019^Citation50	Variations of combined pharmacological, psychological, physical, and other	2 years	✔	✔	✔	✔	✔	✔	✔
Lonergan, 2016^Citation51	CBT, family therapy	1 year	✔	✔	✔						✔
Martin et al., 2017^Citation40	TCAs, antibiotics, 5-HT4 receptor agonists, antispasmodics, antihistamines, H2 receptor antagonists, serotonin antagonists, SSRIs, dopamine receptor antagonist	4 months	✔		✔	✔	✔	✔		✔	✔
Michel et al., 2011^Citation52	Buprenorphine	??	✔		✔						✔
Newlove-Delgado et al., 2017^Citation10	Probiotic-based interventions, fiber-based interventions, low FODMAP diets, fructose-restricted diet	4 months	✔	✔	✔	✔	✔				✔
Ng et al., 2017^Citation65	CBT, relaxation, biofeedback	1 year	✔	✔	✔	✔	✔
Nijhof et al., 2018^Citation69	CBT, relaxation, biofeedback, education, physical conditioning, Pilates, resistive underwater exercises, physical therapy + biofeedback	6 months	✔	✔			✔
Ostojic et al., 2018^Citation80	Physiotherapy, massage, TENS, intrathecal baclofen, botulinum toxin A, cyclic intravenous administration of pamidronate, fentanyl, clonidine, indomethacin, intrathecal morphine, amitriptyline, gabapentin, bupivacaine, ketamine, blocks/epidural, butorphanol, magnesium sulfate, laser therapy, surgery, physiotherapy + pharmacological	2 years	✔	✔	✔		✔			✔
Palermo et al., 2010^Citation53	CBT, relaxation, biofeedback	1 year	✔		✔	✔	✔
Scheper et al., 2013^Citation81	Physical training, Bobath treatment	18 months	✔	✔			✔
Shah et al., 2016^Citation54	Neuroaxial blocks, peripheral blocks, sympathetic blocks, Bier blocks, neurostimulation, intrathecal baclofen, intra-articular steroids	??	✔								✔
Sprenger et al., 2011^Citation61	CBT, family-based, relaxation, biofeedback, yoga	??	✔								✔
Tomé-Pires and Miró, 2012^Citation55	Hypnosis	1 year	✔
Trautmann et al., 2006^Citation66	CBT, biofeedback, relaxation, stress management	1 year	✔
Velleman et al., 2010^Citation56	CBT (CD-ROM, Internet)	6 months	✔	✔		✔	✔			✔
Weydert et al., 2003^Citation57	CBT, famotidine, pizotifen. botanicals (peppermint oil), diet (fiber, lactose avoidance), CBT + biofeedback + fiber	??	✔		✔	✔				✔
Wicksell et al., 2015^Citation58	Acceptance and commitment therapy	3 months	✔	✔	✔
Wiffen et al., 2017^Citation73	Opioids	—	—	—	—	—	—	—	—	—	—
Yeung et al., 2017^Citation79	NSAIDs, TCAs, SSRIs, trazodone or amitriptyline, cyclobenzaprine, laparoscopy, laparoscopic excision or treatment, surgical ablation or excision, surgery + postoperative hormones	??	✔				✔
Zernikow et al., 2012^Citation37 and Häuser et al., 2012^Citation36	CBT, trauma therapy, family therapy, other psychotherapy, aerobic exercises, qi-gong, psychological + physical therapy	5+ years	✔	✔	✔	✔	✔	✔			✔

CBT = cognitive–behavioral therapy; — = no studies; NSAID = nonsteroidal anti-inflammatory drug; ?? = unclear/unknown; TCA = tricyclic antidepressants; SSRI = selective serotonin re-uptake inhibitor; FODMAP = fermentable oligosaccharides, disaccharides, monosaccharides and polyols; - = no studies.

Figure 2. AMSTAR-2 quality ratings of included systematic reviews

Figure 3. Evidence and gap map of interventions for pediatric chronic pain. The figure rows list the types of interventions and the columns list the PedIMMPACT outcome domains. Each cell shows the number and quality of included systematic reviews as assessed using AMSTAR-2 that contain evidence on that combination of type of intervention for pediatric chronic pain and outcome domain

Figure 4. Summary of evidence for top ten patient-oriented research priorities in pediatric chronic pain

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