Definition and Categories of Pain

Pain is defined by the International Association for the Study of Pain (IASP) as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.” The important elements of this definition to be emphasized are (1) pain encompasses both peripheral physiologic and central cognitive/emotional components and (2) pain may or may not be associated with real tissue damage—pain may exist in the absence of demonstrable somatic pathology.

Table 71-1 specifies important pain categories commonly treated (somatic, visceral, and neuropathic) and defines the elements and characteristics of nociception, the peripheral physiologic aspect of pain perception (Fig. 71-1). Nociception refers to how specialized fibers (largely but not exclusively the A delta and C fibers) in the peripheral nervous system transmit nerve impulses (often originating from peripheral mechanoreceptors and chemoreceptors) through synapses in the spinal cord’s dorsal horn through (but not exclusively through) the spinothalamic tracts to the brain’s higher centers, where nociception is converted to pain with all of its cognitive and emotional ramifications.

Table 71-1 PAIN CATEGORIES AND CHARACTERISTICS

Figure 71-1 The typical neural pathways of nociception, also showing higher projection of nociception to the cortex, where the sensation of nociception is translated to the conscious and emotional phenomenon of pain. DLPT, dorsolateral pontine tegmentum; PAG, periaqueductal gray; RF, reticular formation.

The Assessment and Measurement of Pain in Children

Assessing pain entails much more than merely quantifying it. Whenever feasible, the physician should ask the patient about the character, location, quality, duration, frequency, and intensity of the pain. Some children may not report pain because of fears (often well-founded), of talking to strangers, disappointing or bothering others, receiving an injection if they report pain, returning to the hospital if they admit to pain, and other negative reinforcers. For infants and nonverbal children, their parents, pediatricians, nurses, and other caregivers are constantly challenged to interpret whether the children’s distressed behaviors represent pain, fear, hunger, or a range of other perceptions or emotions. Therapeutic trials of comfort measures (cuddling, feeding) and analgesic medications may be helpful in clarifying such a situation.

Behavior and physiologic signs are useful, but they can be misleading. A toddler may scream and grimace during an ear examination because of fear rather than pain. Conversely, children with inadequately relieved persistent pain from cancer, sickle cell disease, trauma, or surgery may withdraw from their surroundings and appear very quiet, leading observers to conclude falsely that they are comfortable or sedated. In these situations, increased dosing of analgesics may make the child become more, not less, interactive and alert. Similarly, neonates and young infants may close their eyes, furrow their brows, and clench their fists in response to pain. Adequate analgesia is often associated with eye opening and increased involvement in the surroundings. A child who is experiencing significant chronic pain may play normally as a way to distract attention from pain. This coping behavior is sometimes misinterpreted as evidence of the child’s faking pain at other times.

Age-Specific and Developmentally Specific Measures

Because infants, young children, and nonverbal children cannot express the quantity of pain they experience, several pain scales have been devised in an attempt to quantify pain in these populations (Fig. 71-2; Table 71-2).

Figure 71-2 Clinically useful pain assessment tools.

(Adapted from Burg FD, Ingelfinger JR, Polin RA, et al, editors: Current pediatric therapy, ed 18, Philadelphia, 2006, Saunders/Elsevier, p 16; and Hicks CL, von Baeyer CL, Spafford P, et al: The Faces Pain Scale—revised: toward a common metric in pediatric pain measurement, Pain 93:173–183, 2001.)

Table 71-2 PAIN MEASUREMENT TOOLS

The Newborn and Infant

There are a range of behavioral distress scales for the infant and young child, mostly emphasizing the patient’s facial expressions, crying, and body movement. Facial expression measures appear most useful and specific in neonates. Autonomic and vital signs can indicate pain, but because they are nonspecific, they may reflect other processes, including fever, hypoxemia, and cardiac or renal dysfunction.

The Older Child

Children 3-7 yr old become increasingly articulate in describing the intensity, location, and quality of pain. Pain is occasionally referred to adjacent areas; referral of hip pain to the leg or knee is common in this age range. Self-report measures for children this age include using drawings, pictures of faces, or graded color intensities. Children age 8 yr and older can usually use verbal scales or visual analog pain scales (VASs) accurately (see Fig. 71-2). Verbal numerical ratings are preferred and considered the gold standard; valid and reliable ratings are for children 8 yr and older. The Numerical Rating Scale (NRS) consists of numbers from 0 to 10, in which 0 represents no pain and 10 represents very severe pain. There is debate about the label for the highest pain rating, but the current agreement is NOT to use the worst pain possible, because children can always imagine a greater pain. In the USA, regularly documented pain assessments are required for hospitalized children and children attending outpatient hospital clinics and emergency departments. Pain scores do not always correlate with changes in heart rate or blood pressure.

The Cognitively Impaired Child

Measuring pain in cognitively impaired children remains a challenge. Understanding pain expression and experience in this population is important, because behaviors may be misinterpreted as indicating that cognitively impaired children are more insensitive to pain than cognitively competent children. Children with trisomy 21 may express pain less precisely and more slowly than the general population. Pain in children with autism spectrum disorders may be difficult to assess because they may be both hyposensitive and hypersensitive to many different types of sensory stimuli, and they may have limited communication abilities. Although self-reports of pain can be elicited from some children who are cognitively impaired, observational measures have better validation among these children. The Non-communicating Child’s Pain Checklist—Postoperative Version is recommended for children up to 18 yr. Maladaptive behavior and reduction in functions may also indicate pain. Children with severe cognitive impairments experience pain frequently, mostly not because of accidental injury. Children with the fewest abilities experience the most pain.

The Treatment of Pain

Both pharmacologic and nonpharmacologic approaches to pain management should be considered for all pain treatment plans. Many simple interventions designed to promote relaxation and patient control can be expected to work synergistically with pain medications for optimal relief of pain and related distress. Psychologic and developmental comorbidities affect the child’s experience of pain and ability to tolerate and cope with it. Thus, it is important to assess a child for evidence of situational anxiety and/or anxiety disorders, such as generalized anxiety disorder, post-traumatic stress disorder, social anxiety, separation anxiety, panic disorder, and obsessive-compulsive disorder (Chapter 23). Depression assessment should include current suicidal ideation and intent as well as past history of suicidal gestures or attempts (Chapters 24 and 25). Developmental assessment includes evaluating for specific learning disorders, Asperger disorder, and evidence of pervasive developmental disorders in general, including autism spectrum disorders (Chapter 28). All psychologic and developmental comorbidities should be determined and addressed, to adequately treat the child in pain or to reduce the risk of the child’s developing ongoing pain after surgery, trauma, or even invasive medical procedures.

FDA, U.S. Food and Drug Administration; IV, intravenous(ly): NSAIDs, nonsteroidal anti-inflammatory drugs; PDD, pervasive developmental disorder; PDR, Physicians’ Desk Reference; QTc, corrected QT interval on an electrocardiogram; SSRI, selective serotonin reuptake inhibitor.

Acetaminophen, a generally safe, nonopioid analgesic and antipyretic, has the advantage of rectal and oral routes of administration, is expected to be available soon also as an intravenous (IV) preparation in the USA, as it is now in Europe. Acetaminophen is not associated with the gastrointestinal or antiplatelet effects of aspirin and NSAIDs, making it a particularly useful drug in patients with cancer. Unlike aspirin and NSAIDs, acetaminophen has only mild anti-inflammatory action. Acetaminophen toxicity can result from either, large single doses or cumulative, excessive dosing over days or weeks (Chapters 58 and 355). A single, massive overdose overwhelms the normal glucuronidation and sulfation metabolic pathways in the liver, whereas long-term overdosing exhausts supplies of the sulfhydryl donor glutathione, leading to alternative cytochrome P-450 catalyzed oxidative metabolism and the production of the hepatotoxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). Toxicity manifests as fulminant hepatic necrosis and failure in infants, children, and adults. Drug biotransformation processes are immature in neonates, very active in young children, and somewhat less active in adults. Young children are more resistant to acetaminophen-induced hepatotoxicity than adults as a result of metabolism differences: Sulfation predominates over glucuronidation in young children, leading to a reduction in NAPQI production.

Aspirin (ASA) is indicated for certain rheumatologic conditions and for inhibition of platelet adhesiveness, as in the treatment of Kawasaki disease. Concerns about Reye syndrome have resulted in a substantial decline in pediatric aspirin use (Chapter 349).

The NSAIDs are used widely to treat pain and fever in children. In children with juvenile rheumatoid arthritis, ibuprofen and aspirin are equally effective, but ibuprofen is associated with fewer side effects and better compliance. NSAIDs used adjunctively in surgical patients reduce opioid requirements (and therefore opioid side effects) by as much as 35-40%. Although NSAIDs can be useful postoperatively, they should be used as an adjunct to, not as a substitute for, opioids in patients with moderate to severe pain.

Ketorolac, an IV NSAID, is useful in treating moderate to severe acute pain in patients who are unable or unwilling to swallow oral NSAIDs. Intravenous ibuprofen is approved in the USA for the management of pain and fever for 5 days or less, although there is no pediatric indication in the package labeling. In Europe, IV ibuprofen is used to treat pediatric pain.

Adverse effects of NSAIDs are uncommon, but they may be serious when they occur. They include gastritis with pain and bleeding; decreased renal blood flow that may reduce glomerular filtration and enhance sodium reabsorption, in some cases leading to tubular necrosis; hepatic dysfunction and liver failure; and inhibition of platelet function. Although the overall incidence of bleeding is very low, NSAIDs should not be used in the child with a bleeding diathesis or at risk for bleeding or when surgical hemostasis is a prominent concern, such as after tonsillectomy. Renal injury from short-term use of ibuprofen in euvolemic children is quite rare; the risk is increased by hypovolemia or cardiac dysfunction. The safety of both ibuprofen and acetaminophen for short-term use is well established (see Table 71-3).

Opioids

Opioids are analgesic substances either derived from the opium poppy (opiates) or synthesized to have a similar chemical structure and mechanism of action (opioids). The older, pejorative term narcotics should not be used for these agents, because it connotes criminality and lacks pharmacologic descriptive specificity. Opioids are administered for moderate and severe pain, such as acute postoperative pain, sickle cell crisis pain, and cancer pain. Opioids can be administered by the oral, rectal, oral transmucosal, transdermal, intranasal, IV, epidural, intrathecal, subcutaneous, or intramuscular route. Historically, infants and young children have been underdosed with opioids for fear of significant respiratory side effects. With proper understanding of the pharmacokinetic and pharmacodynamics of opioids, children can receive effective relief of pain and suffering with a good margin of safety (Tables 71-4 to 71-7).

Table 71-6 MANAGEMENT OF OPIOID-INDUCED ADVERSE EFFECTS

* Avoid in patients taking monoamine oxidase inhibitors.

^† May be associated with extrapyramidal side effects, which may be more commonly seen in children than in adults.

Modified from Burg FD, Ingelfinger JR, Polin RA, et al, editors: Current pediatric therapy, ed 18, Philadelphia, 2006, Saunders/Elsevier, p 16.

Opioids act by mimicking the actions of endogenous opioid peptides, binding to receptors in the brain, brainstem, spinal cord, and peripheral nervous system and thus leading to inhibition of nociception. Opioids have dose-dependent respiratory depressant effects, and they blunt ventilatory responses to hypoxia and hypercarbia. These respiratory depressant effects can be increased with co-administration of other sedating drugs, such as benzodiazepines or barbiturates. What was once thought to represent infants’ particular sensitivity to the opioids’ respiratory depressant effects we now understand to be due to infants’ lower metabolic clearance of opioids and higher blood levels with frequent dosing.

Optimal use of opioids requires proactive and anticipatory management of side effects (see Table 71-6). Common side effects include constipation, nausea, vomiting, urinary retention, and pruritus. The most common, troubling but treatable side effect is constipation. Stool softeners and stimulant laxatives should be administered to most patients receiving opioids for more than a few days. Constipation also remains a problem with long-term opioid administration. A peripherally acting opiate µ receptor antagonist, methylnaltrexone, promptly and effectively reverses opioid-induced constipation in patients with chronic pain who are receiving opioids daily. The side effect of nausea typically subsides with long-term dosing, but it may require treatment with antiemetics, such as a phenothiazine, butyrophenones, antihistamines, or a serotonin receptor antagonist such as ondansetron or granisetron. Pruritus and other complications during patient-controlled analgesia (PCA) with opioids may be effectively managed by low-dose IV naloxone (see Table 71-6).

One of the potent barriers to effective management of pain with opioids is the unrealistic fear of addiction held by many prescribing pediatricians and parents. Pediatricians should understand the phenomena of tolerance, dependence, withdrawal, and addiction (see Table 71-5) and should know that the rational short- or long-term use of opioids in children does not lead to a predilection or risk of addiction in a child not otherwise at risk by virtue of genetic background and social milieu. It is important for pediatricians to realize that even patients with recognized substance-abuse diagnoses are entitled to effective analgesic management, which often includes the use of opioids. When there are legitimate concerns about addiction in a patient, then safe, effective opioid pain management is often best managed by specialists in pain management and/or addictionology.

There is no longer a reason to administer opioids by intramuscular injection. Continuous IV infusion of opioids is one, effective option that permits more constant plasma concentrations and clinical effects than intermittent IV bolus dosing, without the pain associated with intramuscular injection. The most common approach in pediatric centers is to administer a low-dose basal opioid infusion, while permitting patients to use a PCA device to titrate the dosage above the infusion (Chapter 70; Fig. 71-3). Compared with children given intermittent intramuscular morphine, children using PCA reported better pain scores. PCA has several other advantages: (1) dosing can be adjusted to account for individual pharmacokinetic and pharmacodynamic variation and for changing pain intensity during the day, (2) psychologically, the patient is more in control, actively coping with the pain, (3) overall opioid consumption is lower, (4) fewer side effects occur, and (5) patient satisfaction is generally much higher. Children as young as 5-6 yr can effectively use PCA. The device can be activated by parents or nurses—the latter practice known as PCA-by-proxy (PCA-P); PCA-P produces analgesia in a safe, effective manner for children who cannot activate the PCA demand button themselves because they are too young or intellectually or physically impaired. PCA overdoses occur when well-meaning, inadequately instructed parents pushed the PCA button in medically complicated situations with or without the use of PCA-P, highlighting the need for patient and family education, the use of protocols, and adequate nursing supervision.

Figure 71-3 Patient-controlled analgesia is more likely to keep blood concentrations of opioid within the “analgesic corridor” and allows rapid titration if there is an increase in pain stimulus requiring higher blood levels of opioid to maintain the analgesia.

(From Burg FD, Ingelfinger JR, Polin RA, et al, editors: Current pediatric therapy, ed 18. Philadelphia, 2006, Saunders/Elsevier, p 16.)

Local Anesthetics