The treatment of pain is a fundamental aspect in caring for children. Management depends on an understanding of developmental pharmacology; the assessment of acute and chronic pain in children; interventional techniques; and the use of nonpharmacologic therapies, including physical, occupational, and cognitive-behavioral therapies.

Pain can be categorized as nociceptive, resulting from activation of nociceptors by actual or threatened damage to tissue, or neuropathic, resulting from dysfunction of the somatosensory nervous system. Pain may present as acute, chronic, or a combination of nociceptive and neuropathic. Acute pain is a physiologic sensation serving as a warning of disease or danger. Chronic pain, whether recurrent or persistent, is defined by the International Association for the Study of Pain (IASP), as pain that has persisted 3 months or more beyond the expected period of healing.^1–5

Children with chronic pain may have significant school absenteeism, and become socially withdrawn. This in turn may have a long-term impact on their health and development.77 There is evidence that childhood pain that is untreated can transition into adult chronic pain conditions. The economic burden from such unmanaged pain conditions has been extrapolated to be a cost of $19.5 billion in the United States annually.^4,5,7,8

Improving pain control necessitates understanding the pharmacodynamic and pharmacokinetic differences between nonopioid and opioid analgesics in the developing pediatric population.⁹ Several factors result in age-related differences in response to analgesics:

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  Newborns and young infants have a delay of hepatic enzymes involved in the metabolism of most opioids and amide local anesthetics, resulting in a prolonged half-life. Most infants will have maturation of hepatic enzymes by 6 months of age, although there is individual variation.

  
  
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  Glomerular filtration and renal tubular function, involved in the clearance of opioids and their metabolites, are reduced in the first few weeks of life and may affect elimination of these drugs.¹⁰

  
  
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  Newborn and young infants have reduced levels of α-1 acid glycoprotein and albumin proteins. For drugs with high protein binding, such as opioids, reduced plasma protein binding can result in a higher concentration of unbound (active) drug.

  
  
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  Ventilatory reflexes are immature in infants. Infants therefore do not respond to hypoxia or hypercarbia and thereby have increased the risk of hypoventilation from opioids.¹⁰

Assessing a child’s pain experience is critical in developing a comprehensive treatment plan. Pain measures have been developed for children that are based on developmental age and the child’s ability to understand general concepts of pain (Table 42–1).

The assessment of pain in infants is particularly challenging, and pain scales designed for infants and preverbal children typically combine physiological parameters such as heart rate and blood pressure with crying, facial expression, and other observational parameters. The FLACC scale is a widely used, validated pain assessment scale for preverbal children that involves observations of facial expression, consolability, and other behaviors (Table 42–2 and Fig. 42–1).

Several validated self-report pain scores have been developed for children 4 years and older, such as drawings of faces that represent corresponding numerical values of pain intensity (Figs. 42–1 and 42–2).

Most children over the age of 7 years have the cognitive development to use numerical rating scales; however, pain scales designed for developmentally younger children may be applicable for older children who have fear and anxiety while hospitalized (Fig. 42–3).

Pain assessment scales can quantify a child’s measured pain but cannot qualify a child’s comprehensive pain experience.^11–13 The assessment of chronic pain in children must account for multiple dimensions that influence the pain experience, including emotional, cognitive, developmental, behavioral, and cultural factors.^4,14,15 Given the combined biopsychosocial influence of pain, measures of functional impairment and the use of multidimensional pain tools allow for a more accurate assessment of chronic pain. Common multidimensional pain assessment tools in children include the Functional Disability Inventory (FDI) and the child activity limitation questionnaire. The FDI assesses illness and relative activity limitation in children and adolescents with chronic medical conditions.^14,16–18 The Pediatric Quality of Life Inventory (PedQL) is a validated tool for assessing physical, emotional, social, and school function in children 2 to 18 years of age, which includes parent and child reports in parallel.^19,20 The Varni-Thompson Pediatric Pain Questionnaire (PPQ) is another reliable assessment tool for complex recurrent pediatric pain.^19–21,181

Comorbid conditions such as mood disorders, sleep disruption, and fatigue can influence quality of life, and the experience of pain should be assessed as part of a comprehensive evaluation of a child with chronic pain.⁶ The Children’s Depression Inventory and the Revised Child Anxiety and Depression Scale are established tools for measuring depression in children 7 to 17 years old, while the Beck Depression Inventory II is utilized in older adolescents.^2,6,22–27 The Sleep Habits Questionnaire is a tool for assessing sleep in school-aged children.^28–30,170

The management of hospitalized children with pain includes the care of children with acute postoperative pain, as well as the care of children with pain from systemic illnesses such as sickle crises and cancer-related pain.³¹ Taddio et al established that poorly controlled, unopposed noxious stimuli may result in long-term detrimental effects due to central sensitization and the neuroplasticity of the pediatric nervous system.³²

Through their diverse modes of action, multimodal analgesic strategies provide effective analgesia and allow opioid use as rescue analgesia. These can be categorized as nonopioid and opioid analgesia.

Nonopioid Analgesics

Nonopioid analgesics include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and other adjuvants such as gabapentinoids and N-methyl-D-aspartate receptor (NMDA) antagonists. Nonopioid analgesics are often used to provide pain control and reduce postoperative opioid use and opioid-related side effects.^33–36,176 Aspirin should be avoided in children under 16 because of the risk of Reyes syndrome (see Table 42–3).³⁷

Acetaminophen is one of the most commonly used nonopioid analgesics, particularly for its use as an antipyretic. Although the mechanism of action of acetaminophen is not entirely clear, it appears to inhibit cyclooxygenase centrally and activate descending serotonergic pathways. Unlike NSAIDs, acetaminophen has little anti-inflammatory effect or effect on platelet aggregation. It has been shown to reduce postoperative pain intensity, as well as have an opioid-sparing effect^34,38–40 Intravenous, oral, and rectal formulations are available. Preliminary comparison of the efficacy of intravenous administration to oral administration suggests there is no difference in opioid consumption determined by the routes of administration^35,36,39,41

NSAIDs inhibit the synthesis of prostaglandins centrally and peripherally (Fig. 42–4). They are commonly used as a nonopioid analgesic, acting as an anti-inflammatory agent and reducing opioid consumption, resulting in reduced adverse related opioid side effects, such as postoperative nausea and vomiting.^34,38–41 Due to their impact on platelet aggregation, the potential risk of bleeding has been a limiting factor for its use in certain surgical procedures, such as tonsillectomies and neurosurgical procedures. while many centers restrict the use of NSAIDs for post-tonsillectomy pain, the data for its use are mixed.^35,42,43

Although there is limited evidence in children, combining NSAIDs with acetaminophen may afford more effective pain relief than administering either independently. A combination of NSAIDs and acetaminophen is often used for postoperative pain relief. Evidence also suggests that combining these medications has a synergistic effect. When they are not contraindicated, NSAIDs and acetaminophen should be administered around the clock for the postsurgical patient.^34,35,40,41

Gabapentinoids, such as gabapentin, act on the alpha-2-delta subunit of voltage gated calcium channels in the central nervous system. Gabapentinoids can be an effective part of a multimodal approach in managing postoperative pain, reducing pain intensity, and reducing opioid consumption, thereby decreasing the adverse effects from opioids.^44,174,175

At our institution, we administer gabapentin as a perioperative protocol for our spine and hip surgeries.^45,46 There is some evidence that pregabalin may also help to reduce the incidence of chronic postsurgical pain.^33,47

Ketamine, an NMDA antagonist, has known analgesic properties, although the opioid-sparing effects have not been shown consistently for all surgical types.^33,48–51

Epidural analgesia and peripheral nerve blocks are widely used to provide excellent postoperative analgesia and are also used in the management of cancer pain, complex regional pain syndrome, and other chronic pain conditions.⁵² Physiological advantages of regional anesthetic techniques include improved perfusion and an attenuated stress and inflammatory response within the peripheral and central nervous system.^53–55 Dilute solutions of amide local anesthetics such as ropivacaine and bupivacaine are the most common local anesthetics used in continuous regional anesthetic catheters. Neonates and young infants have reduced clearance of amide local anesthetics, and studies have shown that plasma bupivacaine levels continuously rise after the first 48 hours of administration. Chloroprocaine is an ester local anesthetic that can be used as an alternative to amide local anesthetics to avoid the increased risk of amide local anesthetic toxicity in neonates and young infants. Most continuous epidural catheter solutions combine local anesthetics with opioids, such as fentanyl or hydromorphone, or clonidine. Opioids administered in the neuraxis can cause side effects, including respiratory depression, sedation, nausea, vomiting, and pruritus. Clonidine is an α-2 agonist that can provide analgesia when added to neuraxial solutions.^{56,57,189,190} Evidence shows that the addition of clonidine to epidural solutions in children is associated with fewer side effects compared to epidural solutions containing opioids.^{58,178,179,189,190}

Opioids

Opioids are widely used in the treatment of moderate to severe pain in children. Neonates and young infants are at increased risk of respiratory depression and apnea in response to opioids due to reduced metabolism, clearance, and protein binding. Other children at risk for opioid-induced respiratory depression are those with obstructive sleep apnea, neurologic conditions, and craniofacial anomalies. The safe administrations of opioids in hospitalized children requires regular and frequent nursing observation that includes sedation assessment, an understanding of risk factors for respiratory depression, and the use of cardiorespiratory monitoring, particularly for patients receiving continuous infusions of opioids, those receiving neuraxial opioids, and patients who have increased risk of respiratory depression (see Table 42–4).¹⁷¹

Oral administration of opioids should be considered for children who are able to tolerate oral intake. Uptake of orally administrated drugs is through passive diffusion. The rate of diffusion is determined by surface area availability, pH of gastric fluid, and the rate of gastric emptying.⁵⁹ Intravenous administration is the most direct route of giving medications by avoiding hepatic first-pass metabolism and tissue absorption. It is useful for patients with rapidly escalating or fluctuating pain or in those unable to tolerate oral administration.

Patient- and nursing-controlled administration (PCA/NCA) of opioids allows for the delivery of preset doses to be administered on demand by the patient or nurse as needed. PCA has been shown to be safe and effective in children older than 7 years. Compared with continuous infusion, PCA use for acute pain, cancer pain, and vaso-occlusive sickle cell episodes provides similar pain control with decreased overall opioid consumption, thereby reducing unwanted opioid-related side effects.^60,61,180 NCA can be used for infants and older children with cognitive deficits.⁶² Morphine has been extensively studied in the pediatric population in all ages⁶³ and is the most commonly used opioid for parenteral use. Morphine undergoes extensive first-pass metabolism and is converted into the active metabolites morphine-3-glucuronide and morphine-6-glucuronide in the liver by glucuronidation. Morphine-6-glucuronide is excreted by the kidney and can therefore accumulate in patients with renal failure.184 Oral preparations are available in elixir form for younger children who cannot swallow pills and in extended-release tablet forms for older children.⁶⁴

Codeine is a prodrug that is extensively metabolized by the CYP2D6 pathway in the liver to morphine.⁶⁵ Genetic polymorphism of CYP2D6 enzyme activity results in an unpredictable pattern of analgesia from codeine. While some patients may receive no analgesic effect from an equivalent dose, others may develop serious side effects, such as respiratory depression or even death. As a result of the high incidence of potentially fatal side effects, codeine was removed from the formulary at our institution.^64,66,67

Oxycodone is an active compound and, unlike codeine, does not require metabolism for analgesic effect.¹⁰ Evidence shows marked variation in the pharmacokinetics of oxycodone in infants.⁶⁸

Hydromorphone can be used as an alternative to morphine for PCA/NCA use. It is five to ten times more potent the morphine, which is associated with some limitations for PCA/NCA use in lower-weight children.¹⁰ The side effect profile of hydromorphone is comparable to morphine.^{35,69,70,194–201}

Fentanyl is approximately 100 times more potent than morphine as a single dose and 50 times more potent at steady state. Because of its rapid onset and brief duration, fentanyl can be useful for short procedures. When used as an infusion, there is risk for prolonged duration of the effect of fentanyl due to the context-sensitive half-life, which refers to the duration of drug plasma levels after the discontinuation of the drug.^70,185 Transdermal administration can be considered for the treatment of cancer pain in children who are opioid tolerant. Due to the risk of respiratory depression, use requires careful monitoring among providers with experience using transdermal fentanyl in children.

Methadone is a long-acting opioid with a widely variable elimination half-life. Due to its antagonist action at the NMDA receptor, methadone has been used in the treatment of severe neuropathic pain. Despite the wide range of bioavailability, methadone can be useful for its prolonged duration of action; however, it requires careful dose titration and monitoring for oversedation and respiratory depression.¹⁰

Epidemiology

Systematic reviews of pediatric pain show a higher prevalence in girls than boys for most types of pain.^71,72 Abdominal pain and headaches are the most common types of pediatric pain conditions. The prevalence of abdominal pain is almost 25% among school-aged children. The frequency of headaches tends to increase with age in children, ranging from 20% among 5-year-olds and increasing to 75% among adolescents, with a female predominance.⁷³ Prevalence rates for other common chronic pain conditions in children are as high as 24% for back pain and 40% for other musculoskeletal pains. Chronic pain can have a significant impact on the lives of children and their families, resulting in school absenteeism and social isolation with a potential for long-term impact on health and development.^4,5,7,8 Children who are evaluated in chronic pain clinics tend to be those with more severe limitations in function.

Evaluation of a Child with Chronic Pain

The evaluation of a child with chronic pain can be complex, involving multiple physiological processes as well as family, social, and psychological factors. Chronic pain can be persistent or recurrent and may be a result of an underlying disease, or pain can be a primary diagnosis. A key element of the evaluation of a child with chronic pain is developing rapport and a trusting relationship with the patient and family. Details in the history include identifying the onset of pain, characteristics of pain, understanding functional limitations, and performing a psychosocial assessment. Physical examination should be thorough and should assess for signs of chronic illnesses or serious underlying disease that would warrant additional evaluation.

Laboratory and imaging tests to exclude other underlying causes contributing to symptoms of pain should be based on results of a history and physical examination.

Quantitative sensory testing (QST) can be helpful in diagnosing small-fiber neuropathies and abnormal functioning of the various small fibers. It is feasible and valid for children over 5 years of age.^74–77 Functional MRI (fMRI) has been used in pediatric complex regional pain syndrome (CRPS) patients to show changes in central nervous system (CNS) circuitry.⁷⁸

Evidence supports a genetic predisposition in families for developing certain chronic pain conditions. Shared biological family susceptibility to pain, vulnerability, and sensitivity to pain are examples of the possible genetic connection.^79–85 As we advance our ability to identify genetic risk and gene markers, pain genotyping may become a valuable tool for identifying risks associated with pain conditions.^75,80,86

General Principles of Management of Chronic Pain in Children

The guiding principle in managing many types of persistent pediatric pain involves a multidisciplinary approach consisting of a comprehensive evaluation, with patient and family feedback to outline the treatment plan and provide education about chronic pain.⁸⁷ Multidisciplinary teams typically consist of providers in various specialties working together to assess and develop a treatment plan for the patient and family. Disciplines typically include medicine, psychology, physical therapy, occupational therapy, and nursing. They may also encompass alternative medicine practitioners in fields such as acupuncture and massage therapy. The multidisciplinary rehabilitative pain approach is based on a biopsychosocial model of pain accounting for the complex relationship of biological, psychological, individual, social, and environmental factors that affect the recurrent pain experience and often contribute to associated disability.^79,88,89 The primary goal of a multidiscipline pediatric pain program is to improve or restore physical and overall daily function, including school attendance, participation in social and age-appropriate activities, and sleep hygiene.⁸⁸ Evidence has shown a positive impact from this multidisciplinary approach in treating children with chronic pain.^79,88,90,182 Impact was demonstrated by measurement of five out of eight outcome domains recommended by PedIMMPACT: pain intensity, disability, school functioning, anxiety, and depressive symptoms.^1,88,91 Generally, interventions offered by multidisciplinary teams are centered on pharmacologic treatment, physical therapy, and psychological therapy.

Pharmacologic treatment of chronic pain in children and adolescents involves a balance of risk and benefit and should be considered as one part of the multimodal approach. Choice of analgesic depends in part on the underlying disease process. For example, children with arthritis are often prescribed NSAIDs and other anti-inflammatory agents for chronic joint pain. Although anticonvulsants and antidepressants are commonly used pharmacologic agents in the treatment of chronic pain conditions, there are limited data showing efficacy in children. Most safety data are based on use for the treatment of seizures or mood disorders. Low-dose tricyclic antidepressants are sometimes helpful for patients who have pain and disordered sleep; typically a baseline electrocardiogram (ECG) to screen for QT prolongation is recommended.^92–97

Cognitive-behavioral interventions allow for learned self-regulation techniques and cognitive strategies to perceive pain as less debilitating.^88,90 There is good evidence to support the use of cognitive-behavioral interventions for coping, anxiety, and behavior in the management of chronic pain conditions in children, including chronic headaches, abdominal pain, and diffuse persistent musculoskeletal pain.^{6,88,89,91,98–100}

Physical therapy is often an integral part of the multidisciplinary approach to pain. Goals are centered on endurance, core stabilization, joint protective strategies, and desensitization. Transcutaneous electrical nerve stimulators are widely incorporated, although evidence on efficacy is limited. Emphasis is generally on active participation, although passive strategies such as massage may also be helpful (101-102, 123, 139).^{89,91,101,102}

Intensive pain rehabilitation programs, incorporating components of medication and physical and psychological therapy, may provide treatment when goals of physical function and re-engagement are unattainable through outpatient therapy.⁸⁸

Chronic headaches, abdominal pain, and musculoskeletal pain are commonly seen among pediatric pain providers and are discussed next.

Headache

Headaches are common during childhood and can result in significant disability. Reports estimate that 20% to 75% of all school-aged children experience headache.^86,103–105 There is a similar prevalence in males and females in younger ages, and the prevalence increases among adolescent females. The most common forms of headache in children are migraine and tension-type headaches, occasionally with associated occipital neuralgia.

A detailed history and physical examination is of primary importance in the evaluation of a child with headaches. Benign causes of headaches in children are most common; however, recognition and awareness of clinical features that warrant further workup is paramount. The history should include questions to determine the presence of neurologic symptoms such as ataxia, lethargy, seizures, visual impairments, associated symptoms such as depressed mood or aura, and other underlying medical problems such as hypertension and sinusitis. History of a new-onset severe headache, pain that wakes a child from sleep, headaches associated with straining, or change in a headache pattern should prompt further workup, including neuroimaging. Physical examination should include measurement of vital signs, a thorough neurologic exam, and musculoskeletal exam to determine the presence of trigger points and occipital neuralgia, with attention to signs suggestive of systemic disease. Findings of papilledema or focal neurologic deficits mandate additional workup. Routine neuroimaging and laboratory tests are rarely useful, and results of a history and physical examination should serve as a guide to the need for additional testing.^106,107

Migraine headaches are typically characterized as a unilateral throbbing headache that is moderate to severe and often associated with nausea and photophobia. Approximately 25% of children with headache report associated aura. Young children with migraines may present with an abrupt onset of vomiting, photophobia, and abdominal pain, which is relieved by sleep.^108–110

Tension-type headaches typically present with pain wrapping around the head, extending over all areas of frontal, temporal, parietal, and occipital regions. Often, they are associated with significant myofascial pain and contraction of the temporalis muscle with tension of the scalp muscles.¹¹¹

Overall, management involves a multidisciplinary approach consisting of cognitive-behavioral approaches, physical therapy modalities, and thoughtful use of medications in an overall attempt to regain function and improve ability to cope with pain.⁷⁹

Pharmacologic therapy for migraines is directed at abortive and preventive management. Acute pain relief for severe headaches includes NSAIDs, acetaminophen, and triptans for migraine abortive therapy.^112–114 Amitriptyline, topiramate, and propranolol are used for preventive therapy; studies of efficacy have demonstrated mixed results.^114–116 Muscle trigger point injections may be helpful for patients with physical exam findings consistent with musculoskeletal causes of headaches. Patients with evidence of occipital neuralgia may benefit from occipital nerve blocks.¹¹⁰

Abdominal Pain

Chronic abdominal pain accounts for 2% to 4% of pediatric office visits and is one of the most common complaints in children.^117–121 Children with chronic abdominal pain have lower quality-of-life measures compared with healthy peers and are at risk for school absences, social isolation, depressive disorders, and increased somatic complaints.¹²² Functional gastrointestinal disorders (FGIDs) are the most common cause of abdominal pain in children and adolescents, affecting approximately 13% to 20% of children worldwide and accounts for 50% of pediatric gastroenterology visits.^118,119 FGIDs refer to a group of disorders that are diagnosed according to the Rome IV criteria where after appropriate medical evaluation, symptoms cannot be explained by inflammatory, anatomic, metabolic, or neoplastic processes.¹²³

The etiology is thought to be related to central sensitization, and 30% to 40% of individuals with FGIDs have overlapping functional pain disorders such as fibromyalgia or chronic daily headache.¹⁸³ There are also commonly associated symptoms such as sleep disturbances and postural orthostatic tachycardia. Children who present with FGIDs typically have a strong family history of functional bowel or other functional pain disorders. Although there is usually a preexisting genetic vulnerability, in 30% of cases, the FGID is triggered by an infection. A thorough history and physical examination is essential in the evaluation of a child with chronic episodic or continuous abdominal pain. Signs of the abdominal wall as the source of pain such as a positive Carnett’s sign may indicate anterior cutaneous nerve entrapment syndrome. There is some evidence that ultrasound-guided blocks at the border of the abdominis rectus muscle may be of diagnostic and therapeutic value.^124,158 The presence of warning signs such as weight loss, a family history of inflammatory bowel disease, fever, or abnormalities on physical exam may suggest underlying organic disease and warrant consultation with a pediatric gastroenterologist.

Pain-predominant FGIDs are most effectively managed through a rehabilitative, biopsychosocial approach.^119,120 Pharmacologic agents lack strong evidence, although antidepressants may be helpful in select patients with mood disorders or disrupted sleep.¹⁵⁹ Pharmacologic therapy can also help with symptom control, and agents to address constipation, diarrhea, nausea, and spasm are often helpful.^160,161 There is good evidence to suggest that psychological therapy can be effective in the treatment of FGIDs, including biofeedback, guided imagery, and other cognitive-behavioral therapies. Recently, dietary interventions such as the FODMAP diet have become a mainstay of treatment.^125–127

Adolescent females presenting with chronic abdominopelvic pain should be evaluated for gynecologic causes, such as endometriosis, particularly those patients with gastrointestinal symptoms and dysmenorrhea or irregular uterine bleeding.¹²² Evaluation and management of endometriosis include hormonal and surgical intervention while incorporating a multidisciplinary approach for chronic symptoms, including neuropathic agents, physical therapy, and cognitive-behavioral strategies.^{128–131,162,163}

Musculoskeletal Pain

Musculoskeletal pain is a common presenting symptom among school-aged children and adolescents. It accounts for more than 50% of all the recurrent pains reported in the pediatric population.^{18,82,132,133} Pain can be localized to a particular area such as a single limb or it can be widespread and diffuse. Although symptoms can be a result of an initial injury or underlying condition such as hypermobility, in many cases, there is not an obvious source or trigger.^{82,85,101,134} A thorough history and physical examination is essential in the evaluation of a child with musculoskeletal pain, with attention to signs of systemic illness such as fever, growth pattern, and weight loss; signs of arthropathy; and evidence of hypermobility. There is some evidence to suggest that hypermobility-related disorders may have an association with many primary pain disorders.^{102,135–137} On exam, a Beighton score measuring generalized joint hypermobility in children may provide guidance for a patient with diffuse pain and the need for physical therapy.^{102,136,138,139}

Common sources of musculoskeletal pain in children include back pain, chest pain, and diffuse joint pain.

Back pain is relatively uncommon in young children, but prevalence increases in adolescent patients comparable to rates of adult patients.^140,141,169 Etiologies of back pain in children and adolescents are varied and include muscle sprain, spondylolysis, spondylolisthesis, disc herniation, and systemic illnesses such as inflammatory arthropathies and sickle cell crisis.^101,132 A history and physical examination is essential for diagnosis and determination of whether additional testing and imaging are warranted. The presence of fever, anorexia, weight loss, motor or sensory deficits, radicular pain, or cessation of walking in a young child warrants further evaluation.¹⁴² With no concerning signs of infection, tumor, or neurologic disorder, management is most often approached conservatively emphasizing physical therapy for core strengthening and stabilization and ergonomic hygiene.¹⁰¹ Epidural steroid injections are sometimes performed in patients with pain and radiculopathy with radiographic evidence of disc herniation. A retrospective cohort study with prospective follow-up showed that intervention with epidural steroid injection under conscious sedation had good safety outcome and may decrease the need for surgical intervention in refractory cases; however, further studies are needed to define the role of epidural steroid injections in the pediatric population.^143,188

Chest pain typically presents in older children and adolescents.¹⁶⁴ Etiology of chest pain can be differentiated into internal versus chest wall causes or cardiac versus noncardiac causes. Typically, chest pain results in an acute presentation to the emergency department because, although rare, the experience raises the question of the possibility of a serious underlying cardiac cause. Most cases are not associated with an underlying cardiac problem in healthy adolescents.¹⁴⁴

The chest wall is the most common source of pain in teenagers; typically this presents as pain and tenderness along the costal margin and is most often the result of costochondritis. A history of a preceding coughing illness or onset of pain following sports activities supports a musculoskeletal cause of chest pain. Slipping rib syndrome occurs by interchondral subluxation, causing irritation of intercostal nerves and pain. Often, the management of chest wall pain with NSAIDs and reassurance of a noncardiac etiology is successful.

Other sources of chest pain include pulmonary and gastrointestinal. Pulmonary causes are often associated with respiratory symptoms, typically during asthma attacks or respiratory illness. Gastrointestinal causes are most commonly often associated with gastroesophageal reflux.¹⁴⁴

Diffuse joint pain can develop from a localized area that can become diffuse over time with an increase in intensity.^145,165 Children with diffuse joint pain often report a heightened awareness of pain, which becomes a powerful stressor resulting in anxiety.^135,146 Areas of allodynia and hyperalgesia may also develop.¹³⁵ Many children with diffuse pain have associated fatigue, poor sleep hygiene, and low mood, typically as a result of the pain.¹⁴⁷ Diffuse pain in children is often associated with immobilization of the affected area during a time of growth and development of muscles, tendons, and nervous system. Proprioceptive signals from joints and limbs held in fixed position and deconditioning with associated myofascial pain can further amplify central sensitization of the pain pathway.^146,148 In the absence of biomechanical causes or concerns of a systemic process, the approach to managing symptoms relies on physical therapy modalities to improve range of motion, provide joint protection strategies, improve endurance and strength, and restore function. Cognitive-behavioral therapy is helpful in providing coping strategies and to establish school and social reintegration.

Complex Regional Pain Syndrome

CRPS is a condition of a limb pain with neuropathic features. Although exact incidence of CRPS in pediatrics is unknown, some reports suggest it accounts for approximately 20% of pain presentations.⁴ Compared to the adult population, CRPS in children is more common among girls than boys (5 to 7:1) and more often involves a lower extremity (4 to 6:1). The peak age of onset is at or just before the onset of puberty.^149,150 It is more often preceded by a minor injury, and children tend to have a better response to physical and psychological therapies.^76,77,151

According to the IASP consensus terminology, CRPS 1 is a chronic pain condition that is probably due to dysfunction in the central and/or peripheral nervous system and may be sympathetically independent or sympathetically mediated, whereas CRPS 2 results from identifiable damage or disease of the nervous system. CRPS 1 is characterized by pain in combination with sensory, autonomic, trophic, and motor abnormalities.^151,152 Ultimately, the somatosensory, motor, and sympathetic nervous systems have all been implicated in CRPS 1 patients, although the exact mechanism appears to be a multifactorial disorder.^151,152 CRPS 1 is a clinical diagnosis based on the medical history and physical exam. A revised Budapest criteria endorsed by the IASP is used for the clinical diagnosis of CRPS, which has a higher specificity than previous criteria. Validity of the Budapest criteria has been confirmed in adults but not in children.¹⁵³ There are no specific biochemical markers for diagnosis. Laboratory tests and imaging may help to exclude other underlying causes or conditions that may imitate CRPS 1, such as infection, arthritis, and fracture. CRPS 2 presents with a similar clinical presentation; however, because there is damage or disease of a specific nerve, the nervous conduction and electromyographic studies will tend to have positive findings. Bone scintigraphy is not recommended for establishing the diagnosis of CRPS 1 because of low specificity.^74,154 QST is helpful in diagnosing abnormal functioning of small fibers and small-fiber neuropathy but does not confirm or rule out the diagnosis of CRPS.⁷⁴ The main focus of the treatment and management of CRPS 1 is to improve daily function, which is best achieved through active mobilization, desensitization, and cognitive-behavioral therapy. Interventional techniques with peripheral or neuraxial catheters may be useful for select children who are unable to participate in active physical therapy due to severe pain. In these cases, our practice is to place a peripheral nerve catheter or epidural catheter followed by a 4- to 5-day admission for continuous infusions of dilute local anesthetic solutions combined with aggressive daily psychological and physical therapy.^{155,166–168,172,173,186,187,191–193}

In most cases, pain in children is best treated by a multidisciplinary method. Evidence supports safe and effective treatment of acute pain in children with an emphasis on opioid-sparing modalities. Awareness and early diagnosis of primary pain disorders in children and adolescents allow for early intervention and a possible reduced risk of progressing to adult chronic pain conditions. Additional prospective studies are needed in children to better understand optimal analgesic regimens, the prevention of chronic pain conditions and disability, and methods to promote return to full function.