Chapter 54. Chronic Pain in Infants and Children

Management of chronic pain is an essential part of pediatric practice that requires an understanding of pediatric illnesses and the psychosocial aspects of chronic pain conditions experienced by children. Many children experience a variety of chronic recurrent pains such as recurrent abdominal pain or headaches. Chronic recurrent pain is more common in children than persistent pain, and is less likely to be associated with underlying organic disease. Chronic pain may become persistent in conditions such as rheumatoid arthritis, malignancies, sickle cell disease, or neuropathic pain syndromes. Because of the complex nature of chronic pain, treatment is often approached from a broad-based medical model that utilizes the expertise of psychologists, neurologists, anesthesiologists, nurses, and other health care providers. This chapter reviews some of the more common types of recurrent and persistent pain among children and summarizes treatment strategies, including pharmacologic as well as nonpharmacologic therapies.

Recurrent abdominal pain (RAP) is a common problem among school-aged children. Some studies report that as many as 25% of school-aged children will experience recurrent abdominal pain, with the highest prevalence occurring among young girls.1 Many children with RAP remain functional and maintain normal activities; patients seen at pediatric pain clinics are typically those with more severe patterns of pain and disability. In most cases, there is no clear identifiable cause of RAP in school-aged children.1,2

There are certain clinical characteristics that distinguish benign recurrent abdominal pain (RAP) from other types of abdominal pain in children. In general, children with RAP are between the ages of 4 and 16 who experience episodic abdominal pain interspersed with pain-free periods and are otherwise thriving and medically well.2 Children with RAP frequently describe diffuse periumbilical pain that is poorly localized; it rarely radiates to the back or chest. Pain is often worse at night but rarely awakens the child from sleep. Many children will experience other chronic symptoms such as headaches, nausea, and dizziness.

In the majority of cases, RAP is functional, which refers to the lack of an identifiable biochemical, structural, or other organic cause. The lack of a readily identifiable cause for RAP does not imply psychogenic causes. Most children with RAP are in general medically and psychologically well.3 A subgroup of patients will have a recognizable underlying disease, such as lactose intolerance, constipation, ureteropelvic junction obstruction, inflammatory bowel disease, or endometriosis.4–9 For many children, however, an underlying etiology is rarely diagnosed. Some studies have suggested that RAP may be a precursor to irritable bowel syndrome (IBS) in adults, and that some children and adolescents may progress to meet standardized criteria for IBS as adults.10-12

The diagnosis of RAP should be based on a thorough history, physical examination, and review of symptoms. A psychosocial history is essential to learn how the child and family cope with pain and to identify school avoidance and reinforcers of pain. A history of fever, weight loss, growth failure, rash, or other symptoms of systemic illness should prompt further investigation of organic causes.13,14 Occurrence of persistent pain or recurrent abdominal pain in a child younger than 4 years of age is also of concern. A physical examination should include a rectal examination with stool guaiac, evaluation for undescended testes, hernias, and abdominal masses. Findings on history and physical examination that suggest a possible underlying organic disorder should serve as a guide to laboratory and diagnostic testing. In general, extensive routine screening tests such as endoscopies, barium studies, and other radiographic studies are of low yield, particularly when there are no specific clinical suspicions from history or physical examination. In addition to a careful history and physical examination, baseline complete blood count, sedimentation rate, and urinalysis are reasonable screening tests to help rule out occult organic disease. A family history of inflammatory bowel disease in a child with chronic abdominal pain warrants further laboratory and possibly diagnostic testing. In children who experience chronic persistent abdominal pain, rather than the more characteristic episodic pain of RAP, laparoscopy identified treatable conditions in a high percentage of cases.15,16

A significant component of treatment is education and reassurance that no serious organic illness appears likely. It should be emphasized that the child’s pain is genuine and that clinical reassessments will be ongoing. Treatment is based on improving function and reducing maladaptive pain behaviors through emphasis on cognitive-behavioral therapies.17–20 Underlying anxiety or depression should be addressed. A return to school and participation in normal family and social activities is essential. Extensive diagnostic testing and referrals to multiple subspecialists may heighten patient and parental anxiety and reinforce a patient’s “sick role.” Medication trials of tricyclic antidepressants and antispasmodics are sometimes used; however, there is limited data on the efficacy of drug therapy. The routine use of pain medications should be avoided.

Longitudinal studies show that only 30% of children with RAP have resolution of their pain within 5 years and 25% to 50% continue to experience symptoms as adults. Walker and colleagues found that only 1 in 31 children with RAP in a 5-year follow-up were eventually diagnosed with a definable “organic” disease.21

As with many other recurrent pains in childhood, recurrent headaches in children are exceedingly common. As many as 10% of children experience recurrent headaches.22 The most common types of headaches that occur in children include migraine headaches, tension headaches, and combined migraine-tension headaches. Migraine headaches are more common in boys than girls in young children but become more common in girls after reaching puberty. There is often a strong family history of migraines and almost 60% of adults with vascular headaches experienced symptoms during childhood.23 Children with migraines typically report an abrupt onset of unilateral or bilateral severe headache pain that is throbbing and often associated with nausea and vomiting. Although some children may experience classic visual or auditory auras of migraines, many experience more subtle premonitory signs such as pallor, irritability, or fatigue.24 Generally, patients experience relief of the migraine after sleep.23 Tension headaches are most common among adolescents. Usually, there are no associated auras, nausea, or vomiting. The pain is often described as a squeezing pain located circumferentially around the head. It is not uncommon for tension headaches to occur daily. Children with combined headaches experience chronic tension headaches and episodic acute migraine headaches associated with nausea and vomiting.

Most headaches in children are not associated with serious underlying intracranial pathology or organic disease. A thorough history and physical examination is essential and should include a careful neurologic with funduscopic examination. A careful psychosocial history is helpful in understanding family stressors or maladaptive behaviors that may have a causative role in reinforcing pain behaviors. A history of personality changes, visual disturbances, fever, or headaches associated with neurologic deficits are worrisome signs that mandate neuroimaging. A chronic progressive headache or focal symptoms or signs on neurologic examination also warrant neuroimaging to investigate for structural abnormalities or malignancies.

Treatment for headaches in children without underlying pathology includes pharmacologic therapy, cognitive-behavioral interventions, and lifestyle changes that promote functional and adaptive behavior. Reassurance should be provided that a more worrisome cause for the headaches is unlikely and that re-evaluations will be ongoing. Often, a diary that includes characteristics of the headaches, medications, diet, and stress can help identify aggravating factors.

Combinations of analgesics, anitemetics, and 5-HT serotonin agonists are used for abortive migraine therapy in children. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used as first-line abortive therapy for migraines, tension headaches, and combined headaches25 (Table 54-1). Patients should be instructed on proper dosing since excessive use of NSAIDs, acetaminophen, and combination drugs such as Fioricet can cause rebound headaches in some patients26. Systematic reviews of NSAIDs among adult patients report little differences in clinical effectiveness. However, parenteral NSAIDs such as ketorolac are often used when patients have persistent vomiting and cannot tolerate oral intake. In a randomized crossover study, ibuprofen was found to be more effective than acetaminophen for interruptive therapy.25 Ibuprofen in suspension form is commonly used for abortive headache therapy for children who are unable to swallow pills. Recommended pediatric doses are 6 to 10 mg/kg orally. Sumatriptan, a 5-HT agonist, has been shown to be effective for abortive therapy in pediatric patients with severe migraines.27–29 Chronic opioid use is generally not recommended in the treatment of recurrent or chronic headaches.30

Antidepressants, beta blockers, and anticonvulsants are most frequently used for prophylactic migraine therapy. Low-dose tricyclic antidepressants such as amitriptyline or nortriptyline may provide effective migraine prophylaxis. A typical starting dose in children is 0.2 mg/kg administered at bedtime to help promote improved sleep. Doses are titrated on the basis of clinical response and side effects. Trazodone has been shown to be more effective than a placebo in crossover trial but should be avoided in teenaged boys because of the potential for priapism.31 Propranolol is often used in doses of 1 to 2 mg/kg daily; however, controlled studies in pediatric headache management show equivocal results.32,33 Several studies have shown good clinical results with calcium channel blockers.

Essential in the treatment of chronic headaches in children is cognitive-behavioral therapy. Evidence supports the effectiveness of biobehavioral headache management when compared to pharmacologic agents for certain types of headaches in children.33,34 Through biofeedback, guided imagery, and progressive muscle relaxation, patients learn to shift their cognitive focus way from pain and decrease their experience of pain. These skills help to reduce stress and anxiety, which can be precipitating factors for many children with headaches. Cognitive-behavioral strategies help patients learn improved coping skills, return to school, recognize maladaptive behaviors, and help reinforce a more functional lifestyle.

Chest pain in children and adolescents is a common presenting symptom to emergency rooms, general pediatric practices, and pediatric pain clinics, accounting for 650,000 physician visits per year.35 Because chest pain is often an ominous sign among adults, it causes much distress to children and parents. It is, however, uncommonly associated with heart disease in children. Of 67 patients referred to a pediatric cardiology clinic with chest pain, only 6% were found to have underlying cardiac disease.36 Most common causes in children include costochondritis, idiopathic causes, muscle pain from coughing, and other musculoskeletal causes.37,38 Other causes in children include slipping rib syndrome and abdominal and gastroesophageal disease.39

A thorough medical history and physical examination helps to identify cardiac causes. Selbst and colleagues found that organic causes of chest pain in children were more likely if associated with abnormal findings on physical examination, or if symptoms were present in a younger child.37 A history of syncope, presyncopal episodes, or a history of palpitations warrants further evaluation. Gastroesophageal reflux or esophageal spasm may cause referred pain to the chest.

In the absence of worrisome findings on history or physical examination, education and reassurance that heart disease is not a likely cause has been shown to be helpful in long-term resolution of symptoms.36,40 A trial of NSAIDs may be helpful for patients with musculoskeletal causes such as costochondritis. Nonpharmacologic therapies such as transcutaneous electrical nerve stimulation (TENS), heat, progressive muscle relaxation, and physical therapy are helpful for many patients.

Endometriosis is a common cause of pelvic pain among adolescents, affecting 45% to 70% of adolescents with chronic pelvic pain.41,42 In general, endometriosis affects women of reproductive age, but young adolescent girls can experience pain from endometriosis prior to beginning menses. Laufer and colleagues studied adolescent patients with chronic pelvic pain not responsive to conservative medical treatment of oral contraceptives and NSAIDs and found that 70% of patients had endometriosis on diagnostic laparoscopy.41 A variety of other medical conditions such as painful musculoskeletal disorders, constipation, urologic conditions, and irritable bowel syndrome may present as chronic pelvic or abdominal pain.

Many adolescent patients with endometriosis report both cyclic and acyclic pelvic pain. Some patients experience more severe pain at midcycle and with menstruation, but many patients will experience pain throughout the month. There is evidence to suggest that the severity of endometriosis seen on laparoscopy does not necessarily correlate with the severity of pain.43

Treatment of chronic pelvic pain and endometriosis can include hormonal suppression of endometriosis, surgical treatment, effective pain control, and minimizing disability. Hormonal therapy with oral contraceptives and gonadotropin-releasing hormone agonists suppress the growth of endometriosis and inhibit progression of disease. Surgical resection of endometriosis has been shown to provide both immediate and long-term relief from chronic pelvic pain due to endometriosis. Long-term follow-up studies in adult patients after laparoscopic resection of endometriosis show symptom improvement in 66% of patients 5 years after surgery.44

Chronic pelvic pain in female adolescents can lead to significant disability. Over 90% of adolescent women with chronic pelvic pain referred to the Pain Treatment Services at Children’s Hospital, Boston, have endometriosis. A comprehensive approach consisting of biobehavioral therapy, physical therapy, acupuncture, and selected medication trials has been helpful for many patients. As with the treatment of recurrent abdominal pain, emphasis is placed on school attendance, participation in social and family activities, and recognition of maladaptive behaviors. Patients should be thoroughly evaluated for other conditions in addition to endometriosis that may be contributing to pelvic pain such as constipation, irritable bowel symptoms, or urolithiasis. Medication trials of tricyclic antidepressants may be helpful, particularly for patients with sleep disorders, although there is little data on efficacy. Opioids are rarely used for long-term treatment. There is some evidence to suggest that an integrated approach to chronic pelvic pain with attention to organic causes as well as psychosocial factors early in the course of treatment may improve long-term outcome.45

Neuropathic pain conditions in children are most commonly a result of postsurgical nerve injury, extremity trauma, malignancies, complex regional pain syndromes, and congenital and traumatic amputation. Diabetic peripheral neuropathy and trigeminal neuralgia seen in adult patients are rare in children. Clinical features of neuropathic pain in children include allodynia, hyperpathia, and hyperalgesia to noxious, mechanical, and thermal stimuli. Some children will also experience autonomic dysregulation and motor weakness. Children often have difficulty describing neuropathic pain, and will report pain that is “strange” or “weird.”

A thorough history and physical examination, including a careful neurologic examination, is essential when evaluating a child with neuropathic pain. A broad-based evaluation may provide clues to less common causes of neuropathic pain such as underlying cancer, neurodegenerative disorders, or metabolic diseases. Nerve conduction studies are insensitive to abnormalities of C fibers and AÎ fibers, and therefore may be normal in patients with certain neuropathic pain conditions. Quantitative sensory testing (QST), which assesses thermal and vibratory thresholds, may be especially useful in evaluating pediatric patients because it is painless and does not require the use of sedation.46–48

The use of medications in the treatment of neuropathic pain in children is based on data extrapolated from adult studies (Table 54-2). Randomized controlled studies of tricyclic antidepressants have shown effectiveness in treating some neuropathic pain conditions in adults, including diabetic neuropathy and postherpetic neuralgia.49–52 Nortriptyline and amitriptyline are most commonly used in children; desipramine is sometimes a useful alternative if excessive sedation is experienced with other tricyclic antidepressants. Because children metabolize tricyclic antidepressants more efficiently than adults, twice daily dosing is sometimes necessary, although a larger portion of the dose is administered in the evening to help improve sleep disturbances and minimize daytime somnolence. Because of rare case reports of sudden death in children treated with tricyclics attributed to cardiac dysrrhythmias, a thorough cardiac history, physical examination and baseline electrocardiogram is recommended prior to initiating therapy.53 Other antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are occasionally used in the treatment of neuropathic pain; however, additional studies are needed to determine efficacy. SSRIs can be useful for patients who have neuropathic pain associated with depressed mood or anxiety.

Adult clinical trials have shown effectiveness of anticonvulsants such as carbamazepine, phenytoin, valproic acid, and gabapentin for the treatment of a variety of neuropathic pain conditions.54–56 Gabapentin has the advantage of a lower side effect profile and fewer severe adverse effects than other anticonvulsants; monitoring of serum levels is not necessary.57 Most frequent side effects include dizziness and somnolence. Gabapentin may also be effective in the treatment of mood disorders.

There is controversy over the use of opioids in the treatment of neuropathic pain. Some evidence supports that opioids are ineffective in treating neuropathic pain, or that patients experience analgesia only at doses that produce intolerable side effects.58 Other studies suggest that opioids can provide effective pain relief in patients experiencing neuropathic pain from cancer, limb amputation, and other causes without producing unremitting side effects.59–60 In general, the use of opioids in selected patients with neuropathic pain not caused by cancer or other terminal illnesses should involve a treatment plan that emphasizes ongoing cognitive-behavioral therapy and maintenance of school and peer activities.

Complex regional pain syndrome type 1 (CRPS 1) is a condition characterized by persistent neuropathic limb pain with cyanosis, coldness, swelling, atrophy, or other signs of neurovascular abnormalities without an associated nerve injury. CRPS 2 refers to this clinical syndrome with a definable nerve injury.

The clinical presentation of CRPS in children differs from that in adults. Most children with CRPS are female with a lower limb affected, which differs from adult presentation of CRPS, where gender differences are not significant and upper and lower extremities are equally effected. CRPS in children occurs most frequently at 10 to 12 years of age and occurs very rarely before the age of 6. In a report by Wilder and colleagues of 70 children with CRPS, all children were able to identify a specific injury prior to developing symptoms, and some patients developed similar symptoms in a second extremity without additional injury.61 Many patients experienced eating disorders and were involved in highly competitive sports such as ballet and gymnastics.

Several retrospective pediatric series suggest that conservative treatment with aggressive physical therapy and cognitive-behavioral therapy results in marked improvement of symptoms in children with CPRS.62–64 In the Wilder study, a noninvasive approach with physical therapy, TENS, and cognitive-behavioral therapy was effective in improving function and reducing pain scores in over 50% of patients.61 Other studies have emphasized sympathetic blockade.65 A prospective, randomized, controlled trial by Lee and colleagues66 showed that a majority of children had clinical improvement with a regimen that emphasized physical therapy and cognitive-behavioral therapy

The approach at the Boston Children’s Hospital includes an initial outpatient trial of active physical therapy and cognitive-behavioral therapy. Physical therapy is based on a rehabilitative approach involving desensitization techniques, weight-bearing exercises, and a gradual return to function. Cognitive-behavioral interventions typically include biofeedback training, relaxation techniques, and family and individual counseling. Education of both patients and parents is essential regarding the nonprotective nature of pain with CRPS, and that movement of the affected limb will ultimately diminish pain and dysfunction. Regular school attendance and participation in family and peer activities is emphasized. Often, a home diary that records pain scores and measures of function helps track response to therapy.

Commonly used medications in the treatment of CRPS in children include antidepressants, anticonvulsants, local anesthetic-like drugs, and opioids. There is significant individual variation in response to medication trials. Opioids are used in a selected group of patients. Sympathetic blockade is reserved for patients who do not improve with outpatient therapy and who continue to experience significant pain and limitations of limb mobility. Sympathetic blockade is also used for patients who have severe circulatory impairment with ischemic complications. Typically, sympathetic blockade is performed using continuous catheter techniques combined with an intensive rehabilitative 5- to 7-day hospitalization.

Over the past 15 years, more than 650 children with CRPS have been treated at the Children’s Hospital, Boston. Over 85% of patients have experienced pain reduction and good improvement in limb function. Fewer than 5% of patients have received spinal cord stimulation trials or implantations. Fewer than 1% of patients over the past 15 years have received operative or chemical sympathectomies. In all cases, patients underwent sympathectomies to preserve limb circulation rather than for pain control.

Historically, it was assumed that children who have congenital absence of a limb or who have had amputation early in life rarely experience phantom sensations. However, results of several case studies suggest that most children who have limb amputations do experience phantom sensations and pain.67–69 In a retrospective study of children who had undergone amputation, Krane and Heller found that 100% of patients reported phantom sensations and 75% of patients experienced phantom pain.67 A study by Melzack and colleagues showed that approximately 20% of patients who had congenital limb absence and 50% of patients who had amputations at an early age experienced phantom limb sensations.68 There is some evidence to suggest that the children who receive chemotherapy prior to amputation are more likely to experience phantom limb pain than children with amputations who were not exposed to chemotherapy.70

Children describe a variety a phantom sensations such as persistent itching, burning, pain, or a perception of the presence of the missing limb. Some patients will experience allodynia and dysesthesia of the stump.

Studies of tricyclic antidepressants, anticonvulsants such as gabapentin and clonazepam, and opioids have shown effectiveness in treating amputation pain; however, there is limited data on the best treatment among adult and pediatric amputees.61,71,72 Medication trials, biobehavioral techniques, physical rehabilitation, and the early use of a prosthesis have been helpful for many patients.73 Studies examining whether preoperative neurologic blockade reduces the severity or incidence of phantom pain have shown inconsistent results.74–76

Sickle cell pain ranges from acute vaso-occlusive episodes to chronic, daily pain. Acute painful episodes are characterized by an abrupt and usually unpredictable onset of severe ischemic pain. Vaso-occlusive episodes typically produce pain in extremities, chest, lower back, and abdomen, and may be caused by a variety of factors such as infection, dehydration, hypoxia, and acidosis. Often, there is no obvious cause. Acute episodes of pain account for most hospitalizations and emergency room visits. In a prospective study, Platt and colleagues reported that 5% of patients with sickle cell hemoglobinopathy experienced more than 30% of all painful episodes, and that the patients with the highest rates of painful episodes tended to die earlier than patients with lower rates of painful episodes.77 Chronic pain may develop as painful episodes become more frequent and severe, resulting in persistent daily pain. Bone infarction or necrosis may result in debilitating chronic pain conditions such as aseptic necrosis of the hip, vertebral compression fractures, and chronic low back pain.

Home management of vaso-occlusive episodes is encouraged through the use of NSAIDs and orally administered opioids (See Chapter 52). Day treatment programs may provide an effective alternative to hospitalizations or emergency room visits for some patients.78 Hospitalization is necessary for patients who are unable to tolerate oral opioids because of vomiting, or for patients with severe, escalating pain requiring rapid control with intravenous analgesics. Patient-controlled analgesia offers patients the ability to rapidly titrate opioids according to wide fluctuations in pain intensity common in vaso-occlusive episodes (See Chapter 53). A low-dose basal opioid infusion in addition to on-demand doses may provide effective analgesia, particularly during severe episodes of pain; however, there is some evidence showing that this regimen may increase the risk of hypoxemia at night.79 Continuous epidural analgesia can provide effective analgesia and maintenance of respiratory drive in patients with acute chest syndrome.80 It has not been established how often to choose epidural analgesia for patients who have frequent painful episodes. Self-report pain scales should be used as much as possible for pain assessment. Close nursing observation and monitoring is necessary, especially for patients at risk for opioid-induced respiratory depression and hypoxemia.

A multidisciplinary approach to sickle cell pain integrates pharmacologic therapy and cognitive-behavioral techniques to provide effective pain control, maintenance of normal functioning, and optimal quality of life. There is often excessive concern among health providers and families about addiction to opioids, which has led to inadequate analgesia in some cases. Education is necessary regarding the use of opioids, home management strategies, and avoidance of precipitating factors of painful episodes. Cognitive-behavioral treatment such as biofeedback, hypnosis, guided imagery, and family therapy can help to improve coping mechanisms and prevent maladaptive behaviors.81

Patients with cystic fibrosis suffer a variety of recurrent and chronic pains, particularly as lung disease becomes more advanced.82 Recurrent chest pain is common and may occur from chest wall muscle strain, costochondritis, or spontaneous pneumothorax. Severe coughing may produce painful rib fractures that can significantly compromise respiratory function. Frequent headaches can be caused by sinus disease or by the intense contraction of muscles due to coughing. As respiratory function declines with advanced disease, hypercarbia and hypoxia can contribute to headaches.82 Other causes of pain in patients with cystic fibrosis include back pain from compression fractures, arthritis pain, and abdominal pain from pancreatitis.83,84

Treatment of recurrent and chronic pain of cystic fibrosis should provide optimal analgesia without further impairing respiratory function. Opioids may provide effective pain relief without inducing excessive sedation and respiratory depression in selected patients.82 Because patients with cystic fibrosis frequently experience constipation with opioid use, laxatives should be used early in the course of treatment. Selective COX-2 inhibitors may help provide analgesia without causing respiratory depression, constipation, and with less risk of hemoptysis than conventional NSAIDs. Continuous thoracic epidural infusions can provide effective analgesia for rib fractures or pneumothoraces, and for postoperative pain control. Intercostal blockade is less preferred than epidural analgesia because of a short duration of effect and the considerable risk of pneumothorax.

Complementary and alternative medicine (CAM) therapies are increasingly used in pediatric practices and among children with chronic medical illnesses such as cancer and cystic fibrosis.85 In a survey of pediatric pain clinics in North America, 70% of clinics offered at least one form of CAM therapy, and 30% of clinics offered acupuncture services. In a review of hospitalized patients, children were most likely to use CAM therapy for the treatment of pain, nausea, and insomnia.86

Acupuncture is one of the most common CAM therapies and is practiced in a variety of chronic medical conditions including headaches, endometriosis, and nausea. Although children are often reluctant to accept therapy involving needles, even young children report positive experience with acupuncture. One case series reported that 70% of children with chronic pain referred for acupuncture felt that acupuncture treatment helped their symptoms.87 Acupuncture has a very good safety record; there are very rare reports of adverse events. Additional prospective clinical trials are necessary to determine efficacy in children.

Central in treatment of pain and distress in children is an in-depth understanding of pediatric diseases and the psychological and social dynamics involved in chronic pain conditions. Analgesics and specialized techniques should be combined with lifestyle changes and nonpharmacologic approaches to provide optimal care. Additional prospective clinical trials are necessary in the understanding and treatment many chronic pain conditions in children.