Learning Objectives/Outcomes: After participating in this continuing professional development activity, the provider should be better able to:
1. Describe biopsychosocial and environmental influences on the mechanisms of acute and chronic pain in children.
2. Explain the importance of developmental context in treatment of acute pain, prevention of chronic pain, and management of chronic pain conditions.
3. Assess pharmacologic and nonpharmacologic pain management strategies designed for the pediatric populations.
Up to 40% of children and adolescents in the United States report recurrent or persistent pain, which interferes with daily activities and quality of life.1 Pain in children, as with other age groups, can affect physical activity, socialization, nutritional intake, and sleep, among other life functions, especially in children with chronic conditions.2 Due to the developmental trajectory of this age group, pain can significantly affect major developmental milestones, academic performance, and family functioning.
In an effort to reduce the impact of pain in these areas and the risk of chronic pain, a biopsychosocial approach to pain management has been advocated, which highlights the interactions among biological, psychological, and socioenvironmental factors that influence pain perception, coping, and the mechanisms that contribute to chronic pain. Health care professionals across disciplines should be involved in designing and implementing pain prevention, management, and rehabilitative measures for affected children and adolescents. A multidisciplinary approach, using multimodal interventions for pain management across settings, is recommended to improve clinical outcomes, reduce disability, and maintain quality of life in this vulnerable population. This article reviews current research in pediatric pain management and state-of-the-art interventions for health care research and practice.
Biopsychosocial and Environmental Influences on Pain in Children
The biopsychosocial model has been used for several decades to provide a heuristic understanding of the interactions among biological, psychological, and social factors that influence health.3 The biopsychosocial model was a major departure from the classic philosophy of biomedical reductionism that prevailed in medical education since the Renaissance.4 Despite initial criticism, the biopsychosocial model had a significant impact on behavioral medicine and health psychology, and was later adopted by the World Health Organization. A central tenet of the model is the distinction between disease (an objective biological event) and illness (subjective experience) to explain variability in behavior, the symptom experience, and the impact on an individual and family. These concepts, as applied to pain, are analogous to nociception as a biological event, and pain, a subjective experience; and this, in turn, led to its integration in the biopsychosocial theory of chronic pain.4
Recognition that psychological and social factors also impact pain perception went against Cartesian dualism, conceptualized by Rene Descartes in the 17th century. Viewed through Cartesian dualism, the mind and the body were seen as separate, and pain was understood only from a physiological perspective as a sensory experience transmitted from the skin to the brain.4
Building on the specificity theory of pain proposed by von Frey in 1894, and the pattern theory of pain presented by Goldschneider in the same year, the gate control theory of pain by Melzack and Wall in the 1960s was one of the first to recognize the influence of psychosocial factors on pain perception.5,6
Expanding this work, Melzack proposed the neuromatrix theory of pain, which integrates the cognitive-evaluative, sensory-discriminative, and motivational-affective components of pain perception within the genetic background of the individual, producing a characteristic neurosignature referred to as the "body-self" neuromatrix.7 Instead of viewing pain as a consequence of sensory input, the neuromatrix theory posits that pain is an output of the brain neural network; thus, no sensory input is necessary to produce pain.
Within the context of child and adolescent development, the biopsychosocial model of pain depicts interactions that influence the pain outcomes, including well-being and quality of life (Figure 1).
The biological domain includes the individual's personal characteristics, genetic background, health status and comorbidities, and pain severity/duration. The psychological domain includes anxiety, depression, fear of pain, and pain catastrophizing.
In a previous meta-analytic review, anxiety, depression, and quality of life demonstrated a strong association with pain catastrophizing, which was not moderated by age, sex, pain severity, or duration of pain.8 These findings suggest that interventions targeting pain catastrophizing could significantly contribute to improvement in pain outcomes.
The social domain for children and adolescents affected by pain is critically important, both in terms of their development and its impact on pain behaviors. Children are socialized on how to respond to pain. This socialization is carried out by parents, caregivers, and other people with whom they interact, and this socialization can be influenced by cultural beliefs, norms, and preferences that may be different from standards adopted by traditional health care institutions.9 In addition, other aspects of the environment can each influence a child's pain experience and outcomes. These aspects include family support and functioning, exposure to adverse events (such as violence, crime, abuse, neglect, or discrimination), access to nutrition and healthy diet, access to health care, and access to social services. Because all of these factors feed into the experience of pain for pediatric patients, interventions may be targeted toward one or more of these domains in an effort to reduce pain and associated disability.
Pain in children and adolescents-as with adults-may be related to other symptoms, such as anxiety, depression, and sleep disturbances, that affect physical and social functioning (including academics, relationships with peers, and social activities). Sleep disturbances in children and adolescents with pain can be particularly challenging, as poor sleep quality can intensify pain sensitivity and dampen pain inhibition processing, resulting in exacerbation of pain.
This bidirectional relationship between sleep and pain has been studied among youth with chronic pain and sleep disturbances receiving standard care (n = 16) or standard care plus cognitive-behavioral therapy (CBT)-online (n = 17).10 Although no changes in sleep outcomes were observed, the online-CBT group had a significant improvement in pain. Nevertheless, sleep has been identified as a relevant treatment outcome domain for pain management interventions among adolescents by the consensus group PedIMMPACT,11 and more research is necessary to determine adequate interventions in terms of engagement, dosage, and impact on sleep, pain, and other symptoms.
As with development and implementation of any pain intervention, the developmental trajectory of the child and adolescent must be considered. Pain research in infants and children with cognitive impairment demonstrated that these populations often are not provided with analgesics, are undertreated, and that typical behavioral or verbal indicators are not adequate for measurement of pain or evaluation of treatment efficacy.12,13 In addition, the design of the intervention must be age-appropriate, considering issues such as language (verbal and/or written); cognitive, physical, and emotional development; and culturally and racially sensitive (use of props, music, avatars, or other depictions of people with pain).
Procedural and Acute Pain Management
Procedural pain can range from needle injection to bone marrow aspiration and minimally invasive surgery. Although injections are a common experience for young children as part of their vaccination history, needle procedures can have a lasting impression and cause intense anxiety and distress at subsequent encounters.14
Some authors have advised a 3-pronged interventional approach, involving pharmacologic approaches (ie, local anesthetics and analgesics), physical surroundings (ie, calm, relaxing environment), and psychological methods (ie, distraction).13,14
However, due to potential adverse effects in preterm infants, neonates, and children younger than 3 years, nonpharmacologic interventions are typically used, including kangaroo care and music. Among 63 studies included in a systematic review (n = 4905 participants) to assess the efficacy of nonpharmacologic interventions for heel-stick or needle injections, the largest impact on immediate pain regulation was found with nonnutritive sucking, swaddling or facilitated tucking, and rocking or holding.15
A separate review was undertaken to evaluate the effectiveness and safety of pharmacotherapy and combined interventions for reducing vaccine injection pain in children and adults.16 This review demonstrated that topical anesthetics reduced acute distress in children compared with a placebo control, although there were mixed results when comparing topical anesthetics alone to topical anesthetics before and breastfeeding during vaccine injection.16 Acute and recovery distress were lower in children who received sucrose or glucose, although there was no added benefit when compared with nonnutritive sucking or breastfeeding. Vapocoolants reduced acute pain in adults but not in children. Another systematic review and meta-analysis of distraction and hypnosis for needle-related pain and distress in children and adolescents found strong support for these interventions. However, the quality of evidence was low.17
In a meta-analysis and systematic review to examine the effectiveness of distraction compared with standard care/any intervention among children with cancer pain (n = 291), pain was assessed by self-report, observer report, and physiological measures.18 Overall, distraction was found to be as effective as standard care in reducing procedural pain according to self-report and pulse rates, although there was limited evidence based on observer-reported pain.
Of distraction techniques, virtual reality has garnered much attention and has been studied during venous access and for procedures during dental, oncology, and burn care.19 A meta-analysis of virtual reality compared with usual care demonstrated its effectiveness in reducing self-reported pain [standardized mean difference (SMD) = 1.30; 95% confidence interval (CI), 0.68-1.91], anxiety (SMD = 1.32; 95% CI, 0.21-2.44), and pain observed by caregivers (SMD = 2.08; 95% CI, 0.55-3.61) and professionals (SMD = 3.02; 95% CI, 0.79-2.25).
Although virtual reality may also be effective in reducing pain and anxiety in preparation for medical procedures, more research is necessary to assess its use in this context.
In the emergency department, acute injuries can cause significant pain and require immediate intervention. In a double-blind, randomized, active control, noninferiority trial among children age 8 to 17 years with acute extremity injuries, intranasal ketamine was compared with intranasal fentanyl for pain reduction.20 In the trial that included 90 children (n = 45 randomized to ketamine or fentanyl group each), the mean visual analog scale reduction was 30.6 mm for ketamine and 31.9 mm for fentanyl at 30 minutes after administration. Intranasal ketamine was found to be noninferior to fentanyl for pain reduction, and although the risk of adverse events was higher in the ketamine group, all events were minor and transient.
A systematic review of randomized controlled trials (RCTs) on effective pain management for children presenting to the emergency department with musculoskeletal injuries included 8 studies with 1169 children who were 3 to 18 years old.21 Of the studies reviewed that compared oral agents, ibuprofen (10 mg/kg) was more effective than acetaminophen in reducing pain and was comparable to oral morphine (0.5 mg/kg). Oral morphine was associated with a greater number of side effects. Two trials demonstrated that intranasal fentanyl was no different in efficacy to IV morphine. In addition, intranasal diamorphine demonstrated similar efficacy to intramuscular morphine. In terms of sublingual medications, a comparison of sublingual ketorolac failed to demonstrate that either was more effective, although the results trended strongly toward ketorolac. The authors concluded that ibuprofen may be considered as a first choice for mild-to-moderate acute musculoskeletal pain, and intranasal analgesics, such as fentanyl, may be added for moderate-to-several pain.
The authors also recommended that a standardized outcome be used in future trials for pain in children, as these varied significantly across trials and made comparisons difficult. In addition, they recommended additional research on use of nonpharmacologic therapies as adjuvant to pharmacologic management in the emergency department.
Identification of comorbid conditions in children with pain that may necessitate the use of alternative agents or dosing is crucial. For pediatric patients with chronic kidney disease, acetaminophen has been used as a first-line agent for mild-to-moderate pain, whereas buprenorphine may be considered for moderate-to-severe pain.22
Optimal pain and clinical outcomes for children and adolescents undergoing surgery are facilitated by multidisciplinary planning with the child and parents or caregivers to review the procedure, expected level and duration of postoperative pain, available treatment options, and values, needs, and preferences.23 Preoperative premedication-typically using oral midazolam (0.5-0.7 mg/kg)-can reduce anxiety, decrease separation stress, and aid in the induction of general anesthesia. Distraction and relaxation techniques may also be used during the procedure, as well as play or music therapy delivered by child life specialists. These therapies can also be used in the postoperative phase to reduce pain and anxiety as pediatric patients recover. Frizzell and colleagues23 provide a comprehensive review of pharmacologic agents used in the intraoperative and postoperative phase. In addition, Vasquenza and colleagues24 provide an excellent example of a protocol used for patient- and caregiver-controlled analgesia among children undergoing stem cell transplant, a significant challenge that involves an interdisciplinary team approach.
Management of Chronic Pain
Comprehensive pain interventions usually share common features, including pain education, psychological interventions, and physical and/or occupational therapies to improve independence and return to function.23
Pain education (also referred to as pain science education, pain neuroscience education, therapeutic neuroscience education, or explaining pain) is geared toward improving conceptual understanding of pain by the patient and family, and principles of pain management and rationale for treatments. Accumulating evidence in adults demonstrated that increased understanding on the physiology of pain helps to reduce the threat value of pain and can thereby strengthen effective coping behaviors.25,26 Although pain neuroscience education was originally developed for adults,27,28 a curriculum was recently created for children ages 6 to 12 years and is freely available online http://www.paininmotion.be/pne4kids.29
As a stand-alone treatment among adults, pain education is limited by small-to-moderate effect size; therefore, it is recommended as an integrated component of pain treatment.30 A recent meta-analytic review of pain neuroscience education demonstrated that allowing patients to tell their own stories assisted in pain reconceptualization.31
Self-regulation knowledge and skills are a central component of pain self-management interventions.32 These are often combined with relaxation-based strategies such as deep-breathing exercises, progressive relaxation, imagery, and biofeedback, and education in skills for monitoring symptoms, developing and tracking goals, and problem-solving.
For individuals and families affected by pain, self-management should include education on medication management, including the dosing, storage, and titration of medications. Although the specifics of medication management are specific to each individual, there are general principles that should be followed, such as maintaining a log of medications taken, communicating with the individual's primary health care prescriber, and following safety precautions such as avoiding the administration of opioids and benzodiazepines, or misuse of opioids.
This tailored education and monitoring of patient skill attainment, goals, and safety can be enhanced with participation from members of the interdisciplinary team, such as pharmacists and nurses. In addition, self-management may be combined with movement therapies. Mindfulness-based stress reduction, which combines relaxation, self-regulation skills, and yoga, has been found to be effective in reducing pain and disability in children.33
Self-management may include other realms of health, including diet, especially for children affected by functional abdominal pain. The effectiveness of dietary interventions in improving recurrent abdominal pain among 1453 children age 5 to 18 years was examined in a systematic review.34 Among 13 RCTs, the authors found that children treated with probiotics had a greater reduction in pain compared with placebo from 0 to 3 months postintervention and were more likely to have an improvement in pain at 3 to 6 months, with an estimated number to treat of 8. Children treated with fiber-based interventions (5 RCTs) were not more likely to experience a reduction in pain at 0 to 3 months postintervention compared with placebo, and there was only 1 study of a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet.
In addition to providing education and support to the pediatric patient with pain, interventions designed to facilitate parent (or other caregiver) coping have been developed, as parents and other caregivers often experience significant distress associated with seeing their child in pain. Interventions for parents can combine relaxation therapy so that they can practice these skills at home with their child, along with strategies to help shift parental/caregiver attention and behavioral responses toward building coping skills and encouraging function in the presence of pain. A meta-analysis of parental/caregiver interventions demonstrated that these approaches may be beneficial for reducing distress and negative parenting behaviors and improving parent mental health among parents of children with cancer and chronic pain.35
Physical and occupational therapists are also crucial members of the interdisciplinary pain management team. Although physical therapists focus on achieving functional goals with regular exercise, occupational therapists help to maximize independence using age-appropriate activities of daily living, self-care, academics, and family activities. Monodisciplinary pain management focused on physical or occupational therapy has been found to be superior to no treatment. However, monotherapy is inferior to combined physical and occupational therapy with psychological intervention.36
As an example, a 2-arm pragmatic RCT that was nested in a longitudinal open cohort study evaluated the effectiveness of manipulative therapy added to other conservative care for spinal pain in children age 9 to 15 years.37 Of the 238 children randomized to the study, there were no significant differences between participants who received advice, exercises, and soft-tissue treatment, compared with those who received advice, exercises, and soft-tissue treatment plus manipulative therapy. The primary outcome measured was the number of recurrent spinal pain episodes.
Although children in the manipulative therapy group reported a higher global perceived effect (odds ratio = 2.22; 95% CI, 1.19-4.15), there was no significant difference in duration of pain and pain severity. However, the school-based design minimized social bias and provided equal access to manipulative therapy for children with spinal pain. Such interventions may be more successful with integration of problem-solving skills and use of other self-management strategies to increase patient and family self-efficacy in managing pain. In addition, other psychological interventions may be beneficial in reducing perceived pain.
In an updated systematic review to examine the influence of psychological therapies (behavioral or cognitive-behavioral) on pain outcomes among children and adolescents (n = 2884, mean age = 12.65 years, standard deviation = 2.21 years), the authors found that pain frequency was significantly reduced after treatment.38 This was especially the case for participants with headache. However, children with stomach pain, irritable bowel syndrome, fibromyalgia, temporomandibular disorders, sickle cell disease, or inflammatory bowel disease also were included.
The authors concluded that psychological treatments delivered predominantly face-to-face might be effective for reducing pain outcomes for children with headaches or other chronic pain conditions. There were no effects on pain severity identified at follow-up and no effects observed for improving depression and anxiety.
Psychological therapies significantly reduced disability in children with headache at follow-up and in children with mixed chronic pain conditions at posttreatment and follow-up at 12 months.
Based on the findings, the authors recommend that psychological therapies should be considered as part of standard care for children and adolescents with chronic pain, to decrease pain severity and disability.
Expanding this review, the same authors performed a systematic review on the efficacy of psychological therapies delivered remotely compared with waiting list, treatment as usual, or active control treatments for management of chronic pain in children and adolescents.39 For the review, the authors included blended treatments with up to a 30% combination of face-to-face interaction, but primarily delivered via technology, and excluded interventions delivered by phone.
Among 10 studies (n = 697 participants, mean age = 13.17 years) the authors did not find any beneficial effects of psychological therapies for reducing pain severity at posttreatment or follow-up among children with mixed pain conditions. There were no effects on disability, depression, or anxiety.
Overall satisfaction with the remote interventions was positive. However, there is clearly a need for more RCTs in this area, especially because most of these services have transitioned to online due to the COVID-19 pandemic. The authors recommend that trials should assess outcome domains (pain intensity, disability, depression, and anxiety), track adverse events, and report satisfaction with treatment.
In addition, trials among children and adolescents with headache should look for 50% reduction in pain frequency and duration, and intensity for mixed pain conditions, between baseline and postintervention. Doing so will allow meaningful comparisons across research studies.
Addressing Pain Across the Developmental Trajectory
Pediatric pain management is a fundamental aspect of humane and holistic health care. Sufficient evidence has been generated to support the need for analgesic administration for preterm and term infants who are exposed to painful procedures.13 Adjuvant strategies such as kangaroo care, music, nonnutritive sucking, swaddling or facilitated tucking, and rocking or holding should also be used, along with analgesics and local anesthetics to reduce pain in nonverbal populations, as multimodal approaches are recommended. For older children exposed to procedural or acute pain, distraction, hypnosis, and virtual reality can be used as adjuvants to analgesics and/or local or system anesthetics.
Multimodal analgesics also may be required, depending on the severity of pain and procedure(s) involved. Additional research is required to define the clinically meaningful difference (such as a 50% reduction in pain frequency and severity for headaches) that can be used across pain conditions and comorbidities to be able to make meaningful comparisons across research studies.
In addition, more research is needed on integrated approaches to care that use both pharmacologic and nonpharmacologic therapeutic strategies to begin to identify critical thresholds (minimal dosage) for improving pain management for children.
Comprehensive pain management strategies require a multidisciplinary approach to address communication, expectations, and congruence with patient and family values, needs, and preferences. Along with pain education, the use of self-regulation skills, parental coaching, physical and occupational therapy, and psychological interventions can also each contribute to holistic pain management for children and adolescents. More research is needed to examine the dose of pain education and attainment of knowledge that can impact pain outcomes, and which self-regulation skills and modes of parental coaching can improve pain, disability, and quality of life in the short and long term.
Conclusion
Pain management for children and adolescents is a critical aspect of health care across settings, and one that involves multiple disciplines so that coordination of care can be achieved across the continuum. Ensuring that every child receives adequate assessment and management of pain, including the provision of pharmacologic and nonpharmacologic therapies, is essential for pediatric patients across the developmental trajectory.
Although existing studies support the use of multimodal therapies-involving both pharmacologic and nonpharmacologic therapies-little research has been done among children and adolescents to determine best practices in intervention timing, delivery, dosage, and duration. However, consistent with the biopsychosocial model of pain, methods that target multiple domains may contribute to reducing pain severity and functional disability and improve quality of life for the child and adolescent-and for family caregivers.
References