Pain and pain control in children

received his training in Pediatrics at the University of Connecticut. He completed fellowships in Psychosomatic Pediatrics and Developmental Pediatrics at the Children’s Hospital Medical Center in Boston. He is currently Director of the Section of Behavioral and Developmental Pediatrics at Saint Francis Hospital and Medical Center in Hartford, and an Assistant Professor of Pediatrics at the University of Connecticut Health Center. Dr. Schechter’s major interest is in the psychophysiologic problems of children, and his present research concerns pain perception and control in children. Pain has an element of blank It cannot recollect When it began or if there were A day when it was not It has no future but itself Its infinite realms contain Its past, enlightened to perceive New periods of pain. Emily

Dickinson

THE MANAGEMENT of pain in children has been an ignored dimension of pediatric care. Examples of the clinical neglect of children’s pain are manifold. Pediatric procedures (e.g. lumbar punctures, bone marrow aspirations, neonatal circumcisions, etc.) are frequently performed without anesthesia or analgesia. Narcotics for post-operative painI*’ 32, ‘I4 and for debridementlo4 are given far less frequently in children than adults with similar medical problems. Swafford and Allan’s13’ anecdotal comment on the management of post-operative pain in children unfortunately continues to summarize the current clinical approach to children’s pain in general: “Pediatric patients seldom need relief of pain after general surgery. They tolerate discomfort well.” This limited clinical concern with children’s pain is mirrored in the pediatric literature, which contains only one major review of pain control in children.g1 The few additieaal articles addressing pain in children are almost entirely concerned with identifying the etiology of the pain rather than with presenting approaches for pain relief. 6

The reasons for this genera:i tendency to underemphasize pain in children reflect both the nature of the problem and the nature of the treatment. Because of its uniquely personal quality, the symptom of pain has evolved for some beyond its medical implications into a metaphor for human s-uffering and bas assumed a number of societal and religious attributes. For example, some individuals may view the ability to tolerate pain as a sign of strong character and, accordingly, both patients and physicians may be more reluctant to treat pain than other similarly disabling symptoms. Children, whose nervous systems are viewed as less mature than adults and who were seen by some as being less psychologically vulnerable ts pain, are often caught in the middle of these larger philos 1 conflicts and undertreated. Methodologic difficulties and of informed consent in children have further complicate stifled research in this area, which has potentiated cZinicaE neglect. As regards the treatment of pain, societal distrust of medications has focused on narcotics and has been fueled by unwarranted fears of addiction and by daily reports of celebrity misuse of “pain-killers.” Such press has further dampened the enthusiasm to vigorously treat pain. Children, who frequently cannot or will not communicate the extent to which they are suffering, are once again most likely to receive the least rehef. Unfortunately, these attitudes, which travel with the symptom of pain, are based on simplistie and fallacious notions. As a result of them, however, children may suffer needlessly when treatment is easily available. This monograph reviews current concepts of pain and pain control in children. The lack of recognition of pain and its subsequent undertreatment in clinical settings is a major theme of the discussion. Although tbe majority of available research in this field stems from adult literature, implications for children are emphasized pediatric research is highlighted.

The word pain is derived from the Greek “poine,” meaning punishment or penalty, and suggests that the ancients viewed the origins of pain as a response to wrongdoing. Modern definitions of pain are similarly global, such as the standard one offered by The International Association for the Study of Pain Subcommittee on Taxonomy 53 in 1979: ““Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or ribed in terms of such damage.” Bishop’s definition is more ire&-“Pain is what the subject says hurts.“101 Attempting to define pain highlights the nub of the problemthe variability of the pain experience and its lack of direct relationship to tissue damage. Attem ts to order the experience of

pain and provide a uniformity for the sake of definition have been unsuccessful for the most part and are shattered by anecdote after anecdote. Although walking on hot coals or self-mutilation would presumably cause most of us pain, certain religious celebrants report no pain and have none of its physiologic manifestations while engaging in these behaviors. Others report pain and display its physiologic manifestations without any obvious tissue damage-and, in cases such as phantom limb pain, without any obvious tissue. A slap received in jest is often perceived in a different and less painful way than a slap received as punishment, even though both may cause similar tissue damage and stimulate similar nerve endings. Any comprehensive definition of pain, therefore, must take such complexities into account. There are generally two components ascribed to pain: (1) the sensation of pain, i.e., the neurophysiologic message which acts as a warning and tells us tissue damage is taking place, and (2) the perception or experience of pain, i.e., how much suffering the sensation engenders, which is only partially determined by tissue damage and more likely related to social and psychological factors, such as the context of pain, prior experience with pain, personality, and cultural variables. We have understood with increasing refinement the neuroanatomical aspects of pain message transmission for some time, but recognition of the second, more psychological component of pain is relatively new. This knowledge deepens our understanding of the concept of pain for “the impulses in the pain fibers and tracts are no more the pain than the visual impulses from the retina eye are the perceptual fields of color and pattern that present to us when our eyes are open.“86 Any understanding of the complexities of pain must take into account the inextricable interweaving of biologic, psychological, and social factors (Fig 1). A number of categories of pain have been described. A major distinction is made between acute and chronic pain. The relevance of this distinction is less clear in children than adults. Acute pain is typically the result of bodily injury or tissue dam-

Tissue damage Affective state Developmental stage Culture Sex Personality style Past experience with pain Meaning of pain Fig 1 .-Components

~

Pain experience, %uffering”

of the pain experience.

age. It serves as a signal r~r warning that such taken/is taking place and directs the individual’s attention to it. Chronic pain is the persistence of pain symptoms for a prolonged period of time, usually 6 hs. Chronic pain no longer has a biologic warning function a becomes maladaptive, often coexisting with depression, whi exacerbates the pain. The classic example of chronic pain ’ adults is low back pain, which was a problem in over 17 million Amerestimated by Bonicalg to icans, at a cost, in terms isability, work days lost, and health care costs, of $17.6 billion yearly. Children rarely have chronic, continuous, disabling pain. Tneir chronic pains are primarily recurring or “periodic” pains, such as limb pain, headache, or recurrent abdominal pain are as disabling as is chronic pain in adults. This mo uses primarily on acute pain in children and its trea only briefly mentions chronic pain.

The anatomical, biochemical, an physiologic details of t nervous system structures presumed to be responsible for transmission of pain information have gradually become better defined. The peripheral nerve endings, or receptors, which receive unpleasant stimuli, are found in the skin and organs and funcor thermal stimulation tion to convert chemical, mechanical, into electrical activity. Three of receptors have been identified: thermoreceptors, mech eceptors, and nociceptors, or pain receptors. The mecha~~~ece~tors and thermoreceptors consist of either encapsulated receptors or free nerve endings, have a low threshold, and are the terminals for large myelinated nerve fibers. In contrast, ~ocice~tors are typically unmyelinated and unencapsulated and respond only to a level of stimulation sufficient to cause tissue damage, such as strong mechanical deformation or hot (>50” C!> or sold (~15” C) temperatures. Because most nociceptors respond to various types of painful stimuli, they are known as ~~~yrn~da~ nociceptors. Nociceptors are connected to the spinal cord by two specific types of nerve fibers: A delta fibers (class 1) and @ fibers (class 4). The thinly myelinated A delta fibers conduct impulses more rapidly and are associated with sharp initial pain, while the unmyelinated, more slowly con ucting fibers are associated with second, or slow, dull pain. The relative absence of myelin on both of these types of fibers makes them more sensitive to infiltration of local anesthetic agents than would be more myehnated fibers.51 The larger, rapidly conducting A alpha and beta fibers are activated by mechanoreceptors and are concerned with more benign sensations, such as a touch and light pressure. A delta and C! fibers enter the spinal cord through the dorsal horn. Based on its anatomical and functional characteristics, 9

this structure has been divided into six laminae. Sensory input from A delta and C fibers enter into laminae 1 and 5, and possibly 4 and 6. 51 The larger myelinated fibers enter the dorsal horn via a more circuitous route, primarily through laminae 2 and 3, which are known as the substantia gelatinosa. In the dorsal horn, and perhaps most specifically in the substantia gelatinosa, additional neurons may be interposed between the afferent nerve, which has been stimulated by the receptor, and its eventual projections throughout the CNS. These interposed neurons may exert modulating effects on the conduction of painful impulses. This information forms the evidence for the gate theory of pain transmission, which will be discussed in detail shortly. Information from the dorsal columns is transmitted via a variety of routes to the brain. Although Lissauer’s tract and the lemniscal system appear to have some role in pain transmission and its modulation, the major athway for pain conduction is the spinothalamic system (Fig 2). P, This tract is believed to consist of two distinct subsystems-the neospinothalamic tract and the paleospinothalamic tract. The neospinothalamic tract begins at the synapse in the dorTo Limbic System and Cerebral Cortex

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sal horn, crosses the eontrak~teral side of the cord, and then ascends in the lateral portions of the cord to the posterior thalamus. Here, synapses occur, and further fibers are projected to the primary somatosensory centers. This tract appears to transmit localized, acute pain messages to the brain. The paleospinothalamic tract is older phylogenetically and located more medially. It is thought to be responsible for transmitting chronic pain messages. It emerges from laminae 1 and 5 of the dorsal horn, passes through the reticular formation, and sends branches into the hypothalamus, medial and intralaminar thalamic nuclei, and limbic forebrain. This involvement with the limbic system may in part e responsible for the emotional suffering associated with pair~.~~’ 51 After crossing the medulla, the pain fibers enter cerebral hemispheres. Projections of pain fibers reach most aspects of the brain. Cortical activity has a limited role in the initial recognition of pain, which is probabl exive in nature, but it appears to have a major role in the sequent interpretation and response to pain. Past experien expectations, and emotions are called into play through projections to the frontal cortex and limbic system and appear to have a significant role in our response to pain messages. Finally, there does appear to be a descending control system that can modify pain transmission. Much evidence exists that supraspinal descending systems can influence transmission of pain information at the dorsal horn and at numerous sites along escending tracts, which were previthe ascending pathways. ously assumed to be solely motor pathways, have been shown to influence ascending pain transmission. The mechanism of this phenomenon remains unclear, but a graphic example is available through the electrical stimulation of the periaqueductal gray region in the brain, which produces significant analgesia, equivalent to that achieved with high doses of morphine. Although detailed mechanisms remain unclear, this descending pain control system can bl k transmission of nociceptive information at the level of the rsal horn from entering the spinothalamic tract.

The chemistry of pain transmission is intimately related to its anatomy through neurotransmitters, the substances responsible for message transmission across the synapse. The primary neurotransmitters in pain transmission are the monamines (norepinephrine, dopamine, and serotonin), substance P, and the endogenous opioids (endorpbins and enkephalins). The monamine substances, in particular serotonin, may have an important role in descending pain control systems. Anesthesia caused by electrical stimulation of the periaqueductal II

gray areas can be obliterated by the administration of tetrabenzine or P-chlorophenylanine, substances that reduce levels of monoamine transmitters.i’ This and other work supports the notion that descending pain modulation pathways may be serotonergic and also explains the fact that decreased levels of serotonin often correlate with increased pain and depression. Dopamine has been implicated as having a role in ascending pain transmission.r7 Substance P, a peptide initially isolated from brain and gut, has been isolated from a population of C fiber terminals. The small unmyelinated C fibers carry solely nociceptive information, and therefore substance P is presumed to be an important neurotransmitter for pain fibers and to have a potential role in the modulation of pain messages.72 A major thrust of current research concerns the endogenous opioids. Specific opiate receptor sites were first described in 1973 by three laboratories almost simultaneously.138 Subsequently receptor sites were found to exist in all vertebrates examined. The existence of receptor sites for a foreign substance such as opium led scientists to speculate that an endogenous substance with properties similar to opium must exist. Shortly thereafter, Hughes, Smith, et al. in 1975 described pentapeptide endogenous opioids in the CNS which they termed enkephalins (“in the were quickly identified that head”) .52 Two similar enkephalins differed only in their terminal amino acids-methionine or leutine. Cox et al.2g soon described endogenous opioids outside the CNS, in the pituitary. The generic term endorphin (endogenous morphine-like material) was soon given to all endogenous opiate-like peptides. In general, the enkephalins are short pentapeptides and the endorphins are longer chain peptides. The most important endorphin is /3 endorphin, also known as C fragment. Identical amino acid sequences to those of the enkephalins and endorphins are found in p lipotropin, a pituitary peptide that may serve as a prohormone for some of the endorphins. The enkephalins and endorphins are distributed quite differently throughout the body. Enkephalin cell bodies and terminals have been found in the substantia gelatinosa of the dorsal horn of the spinal cord, the marginal layer of the trigeminal nucleus, in the raphe magnus, and in the periaqueductal central gray area. 13r Enkephalin-positive fibers are also present in the gastric mucosa, duodenum, gallbladder, cystic duct wall, and lower intestine.71 Low levels of enkephalin have been found in the liver, kidneys, and atria of the heart. l3 endorphin, however, appears to have a higher concentration in the pituitary, in particular in the pars intermedia and the pars distalis.r31 In the CNS, l3 endorphin is found primarily in the arcuate nucleus, with long axons innervating midbrain and limbic structures.71 The exact role and mechanism of action of the endorphin sys12

tern remain unclear. It pears that enkephalins are involved in the short-term inhibiti of neural activity (such as pain transmission), while p end~r~~i~~ may have a similar role in more extreme injury and may act for longer periods of time. Support for these premises comes from a variety of sources. The electrophysiologic and pharmacologic work demonstrating transmission modulation by enkepbaiin in the substantia gelatinosa of the dorsal horn’ is an irn~o~a~t source of our understanding of the function of enkepbalins. The potent analgesia that is obtained through stimulation of the periaqueductal gray area results in a marked increase in endorphin concentration in the third ventricle,71 suggesting a cerebrospinal fluid (CSF) of t role for p endorphins in pain control. In addition to pain control, the endorphin system appears to have a role in control of motor activity, body temperature, and neuroendocrine functioning. Studies have implied relationships between endorphins an schizophrenia, and between endorpbins and sudden infant death syndrome. Although the study of endorphins is just beginning, the explosion of interest should provide further clarification of the complexities of this system and perhaps will be of practical value in the near future.

‘The complexities of pain transmission suggest the need for an overall theory of pain beyon basic details of neuroanatomy and neurochemistry. Three major theories have arisen during the 20th century to explain the available data about pain transmission. The classic theory, known as specificity theory, proposes that the experience of pain is the direct result of a fixed, direct-line communication system from skin to brain. The A delta and C fibers pass messages to the lateral spinothalamic tract in the cord onto a pain center in the brain. This implies an invariable relationship between stimu1u.s and sensation, i.e., the quality of the pain experience is entirely determined at the pain receptor. Accordingly, a painful stimulus should always evoke a similar pain response proportional to the initial input if all aspects of the patbway are intact. This theory is inadequate to explain many observed clinical phenomena. Interruptive surgical techniques do not uniformly eliminate pain, despite interrupting the theoretical route of transmission. Phantom limb pain, causalgia, hyperalgesia, and pain from “‘trigger zones” which spreads unpredictably all refute such a rigid relationship. Fin.ally, the enormous variability in the sycbological relationship between pain perception and stimulus intensity suggests that the specificity theory of pain is an inadequate unifying theory. The pattern theory of pain evolved out of attempts to address the inadequacies of the specificity theory. The pattern theory 13

has at its core the concept of central summation; that is, not only is the intensity of the direct stimulus important, but the possibility of an additive effect of sensory inputs at the dorsal horn exists. Spontaneous pain could, therefore, occur from seemingly nonnoxious stimuli that combine to reach a critical threshold. This theory explains phantom limb pain and other phenomena in which pain occurs after stimulation has ceased, and can even explain referred pain in phenomena such as the “dorsal root reflex,” in which nonnoxious input could elicit abnormal firing of receptors that could be interpreted centrally as pain. Although the pattern theory overcame some of the objections to the specificity theory by explaining how pain could occur long after the stimulus was gone and in response to seemingly nonnoxious stimuli, both theories emphasize the transmission of pain messages peripherally and provide limited insight into the experience of pain. Melzack and Wall,s5 writing in 1965, proposed the gate theory of pain in an attempt to explain the variable relationship of pain to the stimulus that produced it. They thought that the specificity theory could not account for the variation of pain phenomena clinically and that the pattern theory ran contrary to available physiologic information. They tried to “propose ways in which . . . psychological phenomena could be related to the rigid, stimulus bound response properties of the peripheral nerve. . . . In the real world outside the laboratory, the variation of the relationship between pain and injury occupies all positions between injury with no pain and pain with no injury.“’ ’ According to the gate control theory, transmission of information about injury from the peripheral nervous system to the CNS is controlled by a variety of factors. Melzack and Wall suggested that presynaptic inhibition or facilitation (“gating”) of the pain message could take place in the dorsal horn, probably in the substantia gelatinosa, and could modify transmission of pain information. They proposed two mechanisms for this modulation: (1) the inhibition of pain transmission by the simultaneous stimulation of low-threshold afferents that carry benign information, such as light touch, and (2) the facilitation or inhibition of pain messages by descending control; that is, modulation through descending channels in the CNS. The gate control theory, therefore, allows specificity within the nervous system but explains the wide range of pain perceptions. Many aspects of the gate control theory have been supported by further research. The usefulness of transcutaneous electrical stimulation in pain control by stimulating low-threshold fibers to obliterate pain is clearly evidence for the inhibiting role of the larger myelinated afferents. Apley5 has even suggested that maternal rubbing or kissing of a child’s injury relieves pain not only by providing compassion and security, but also by stimulat14

ing larger afferents and ~~~d~~at~~g pain transmission, as predicted by the gate control t The notion of descending control gains strong support from work on stimulation of the periaqueductal gray system, which causes analgesia, and from work in decerebrate animals in which descending control from the pons and medulla can inhibit the effect of cutaneous afferents directly at the dorsal horn. Other studies have suggested that the level of arousal in the CNS can have a direct effect at the dorsal horn as well. These central mechanisms explain, at least theoretically, how anxiety, depression, context of pain, learned behaviors, and previous experience of pain may have a direct effect in an individual through descending control mechanisms which could modify the amount of suffering that an individual perceives. Certain aspects of the gate control theory remain contra sial. The location of the gate, for example, and WhQthQr mo cation is presynaptic or postsynaptic remain unknown. Although details are sketchy, l~od~fication of the transmission of pain information clearly occurs along the pathway, and this theory supports many of our clinical impressions about pain.

Because of the subjective, personal quality of pain and the lack of a linear relationship between pain and tissue damage, its precise measurement has proved difficult. Pain assessment is important, however, for diagnostic and treatment purposes, and to determine analgesic efficacy. Several methods of quantification have been attempted, but at present, most have sbortcomings, particularly when applied to children. One approach to measurement of pain has been the use of experimentally induced ain. In the laboratory setting, pain is induced in subjects by mechanical, chemical, electrical, thermal, or ischemic stimuli. Pain stimuli can be controlled and the subjective and physiologic responses of the subjects can be measured. Experimentally induced paan has limited practical implications, however, because it does not easily equate with clinical pain. The typically attendant anxiety about the disease process that occurs with clinical pain is not a component of experimentally induced pain, when the subject knows the experiment is limited and can be stopped at his or her insistence. Clinical pain, of course, has no such constraints, and attempts to equate laboratory-induced and clinical pain have not always been successful. For example, morphine appears much more effective elini@ally than in the laboratory, where Beecher reported it cannot be distinguished from saline.” A number of clinical tools have also been developed. Melzaeks4 15

and colleagues developed the McGill Pain Questionnaire, which assesses a variety of pain characteristics in three major areas: (1) sensory (temporal, spatial, etc.), (2) affective (anxiety, depression, etc.), and (3) evaluative (subjective intensity rating scales). Tessler et al. combined portions of the McGill Pain Questionnaire with other, more child-oriented questions to develop the Pediatric Pain Questionnaire.132 A major thrust of current interest is the visual analogue scale. Patients mark on the scale, from no pain to extreme pain, where the pain they are presently experiencing falls. The scale provides a graphic representation for the patient and health care staff of the magnitude of the patient’s degree of pain and can aid in titration of analgesics. This visual analogue scale has been modified by Katz et a1.64 for children over age 8 in the form of a “pain thermometer” on which children mark their degree of pain (Fig 3). Despite modifications for c ildren, the pain assessment techniques described so far require substantial patient cooperation, which may not be available in the frightened pre-school-aged or preverbal child. Alternative measurement techniques that have potential clinical relevance bave been reported. Katz, Kellerman, and Siegel65 developed a 25item observational distress scale which they felt measured the degree of pain and anxiety (a construct they labeled “distress”) in children undergoing bone

Fig 3.-Children’s pain self-report measure: pain thermometer for pain during bone marrow aspiration. Zero means the child felt no hurt; and 100 means the child felt most hurt possible. (From Katz EL.: Distress behavior in children with leukemia undergoing medical procedures. Presented at the American Psychological Association Symposium, New York, September 1979. Reproduced by permission.) 16

marrow aspiration. This scale was subsequently modified by Jay et a1.58 into the Obs~rvat~o~a~ Scale of Behavioral Distress (OSBD), which bas 13 viors (such as crying, screaming, flailing, or muscular rig that are weighted by intensity and thereby offer a standa means of assessing the degree of pain a child may be ex~er~e~~i~g. Two interesting pbysio~o~i~ measures have recently been reported that may event ally have clinical relevance. Levine and Gordon76 have reporte using spectrographic analysis of infant pain cries, which the e are unique and unlike cries of discomfort and hunger. Sue “‘pain-induced vocalizations” have previously been described in primates. Harpin and Rutter47 have described the dev ent of “emotional” palmar sweating in newborns over 37 s’ gestation. This sweating occurs when the infant is subjec to painful stimuli, such as heel pricks, and is responsible in some measure for increased galvanic skin conductance. They suggest that such a technique may provide objective evidence that a newborn is being distressed, even though we may see no other signs of that distress. It may be seen, therefore, that there is an increasing reco tion that children experience pain, and this recognition has yielded some preliminary research attempting to measure the degree of pain children may be experiencing. The remainder of this monograph reviews some of the current thinking about pain experiences and pain control. ACTORS

THAT

OF

A variety of factors have been identified that appear to alter the perception of pain and, accordingly, modify the experience of pain. Because of the co plexities of objectively measuring pain and the uniquely private sensation it represents, much of the following information remains controversial, but the weight of evidence suggests that factors unrelated to the amount of tissue damage may have a major role in determining the amount of suffering that a given ~ai~~~~ stimulus evokes. The majority of this work comes from the adult literature, but it is reviewed here because of its irn~~i~a~i~n~ for children. CONTEXT

cw PAIN

A classic study by specificity theory an control theory. Bee during World War I soldiers he cared for its easy availability. that 82% of civilians w quested pain relief. After

a major challenge to the nderpinning of the gate esthesiologist working at Anzio at only 25% of the 215 wounded narcotic relief from pain, despite ing to the United States he noted undergone similar operations reinterviewing these patients, 17

surmised that the context or meaning of pain was a critical variable in the perception of pain. For the soldiers, pain was representative of injuries received for valor and offered a ticket home. For the civilians, pain represented potential disability and an uncertain future. Subsequently a number of other studies have failed to show a linear relationship between the severity of a surgical procedure and the amount of pain it appeared to engender . Bruegel” reported that the amount of pain experienced in his study was highest for persons who had undergone gastrointestinal surgery and lowest for those who had undergone cesarean section. The context or meaning of pain to the patient appears to have a major modifying role in the perception of pain. In a similar vein, Beales et al7 examined the pain perceptions of 39 children with juvenile rheumatoid arthritis who were divided into a younger (ages 6-11 years) and an older (ages 1217 years) group. He found that although younger children reported sensations (warm, sharp, etc.) similar to those reported by the older group, they did not attribute unpleasant meanings to these sensations and, accordingly, did not find them as painful. In the older group, the sensations served as reminders of the child’s disabling condition and were perceived as painful. In the younger patients, who were cognitively less able to conceptualize internal pathology, the sensations were devoid of negative connotation and were therefore less painful. SEX In interpreting the literature on sex differences in pain responsiveness, understanding the distinction between pain threshold and pain tolerance is critical. As defined in the laboratory, threshold denotes the point at which an individual reports a stimulus as painful, while tolerance is the point at which a stimulus is no longer tolerable for an individual and he or she will refuse to accept the continuation of that stimulus or an increase to a higher magnitude of stimulation. The difference between threshold and tolerance is known as pain sensitivity, or pain duration range.14’ It appears as though threshold is associated primarily with physiologic variables, while tolerance is related more to psychological variables. While most studies designed to examine sex differences in pain perception find no differences in threshold response between men and women, there appears to be a difference in tolerance of pain.g2 For example, in a study by Woodrow et al. of 40,000 people, men were able to tolerate a greater amount of pain stimulus (pressure on the Achilles tendon) than women.143 The interplay of biologic factors and social expectations in this area is obviously enormous and has not been sorted out. For ex18

ample, social cognitive factors such as belief systems and rules appear to mediate responses to pain in certain situations. Pilowsky and Bondlo” report that women were more likely than men to be given analgesia on bospital staff initiative without necessarily requesting it, in part, at least, because of the perceived societal expectation that men should be able to endure more pain than women. ETHNIC FACTORS Ethnic and cultural factors have long been assumed to con-tribute to an individual’s response to pain. Cultural expectations would appear to define how much pain is acceptable to an individual before he or she can corn lain, when an individual is permitted to cry, male versus female responses to painful situations, pain language, and amount of emotionality. The pioneering work i was done by Zborowski1”4’ 145 in the 1950s and 1960s. ted to identify differences between four ethnic groups “‘old Americans,” and Irish) in response to clinical pain of theoretically similar origin. l3e found that in general, Jews and Italians tended to demonstrate more emotional sponses to pain, to be less inhibited in demonstrating pain, a to be less tolerant of it than the other two groups. Zborowski nd differences between the Jewish and Italian groups as well. Italians appeared to respond more favorably to analgesics th ewish patients because they had a “present” orientation were concerned with the here-anda “future” orientation and were connow. Jewish patients cerned with their future functioning, and, accordingly, were less responsive to medication. “‘Old Americans” (white Anglo-Saxon Protestants whose ancestors came to the United States more than three generations ago) tended to be more “matter-of-fact” and precise about their pain with health care providers. They desired solitude when the pain became severe or when they wanted to cry. It was important for them not to appear weak or helpless. Irish patients were reluctant to discuss their pain and would frequently deny it. They believed that such troubles were not to be shared with others Subsequently, similar WOK has been done with black Americans, Puerto Ricans, Eskimos, American Indians, and Asiatics. In many of these studies, there are discrepancies between response style to laboratory-induced pain versus disease- or procedure-induced pain. Zborowski’s studies and many of the others performed were descriptive in nature and did not use standardized pain experiences or objective pain rating scales. In studies where the pain was induced in the laboratory, the examiner producing the pain and recording its results was not necessarily of the same ethnic 19

background as the patient. It has been shown that such factors can greatly influence one’s response to pain. For example, Buss and Portnoyz4 have reported, after obtaining baseline data on pain tolerance for a group of patients, that if patients were given false norms for their reference group (“Russians have a greater tolerance for pain than Americans”), they tended to increase their pain tolerance. Other investigators have looked at childrearing practices in regard to parental responsiveness to a child in pain and report that while Italian and Jewish mothers tended to encourage expression of pain, to give words to pain for their children, Irish and “old American” mothers tended to discourage expression of pain. In a recent study Flannery and colleagues38 attempted to control for some of the methodological flaws that have plagued this literature. They examined the responses of 75 women to episiotomy pain, using a variety of outcome measures. Five ethnic groups (blacks, “old Americans,” Jews, Italians, and Irish) were examined. They found no statistical difference between the groups in response to the same painful procedure. Flannery’s group postulates that in part the results suggest the gradual diminution of certain characteristic ethnic traits and the assimilation of dominant “old American” values. They suggest that while the original research in this area was often done on immigrant or first-generation patients, they used as subjects second- and third-generation Americans whose values are much more similar to the mainstream values of this society. Cultural differences in response to pain are emphasized here, not to reinforce old stereotypes or create new ones, but to demonstrate yet another manifestation of the complexity and uniqueness of our response to pain. Clearly cultural expectations and standards have a role in the experience of pain. PSYCHOLOGICAL VARIABLES A variety of psychological variables have been found to have a role in modifying the perception of pain in the individual. These appear to fall into two categories: (1) personality styles that are more “pain prone,” and (2) emotional or affective states, which can influence pain perception. A thorough review of these areas is beyond the scope of this monograph but may be found in other sources.14o Much work has been done regarding the “pain-prone” patient: the individual who, because of personality, appears to be more vulnerable to pain. These personality styles have been examined in a number of ways. The Minnesota Multiphasic Personality Inventory (MMPI) has been used by many investigators in an attempt to identify homogeneity in chronic pain patients. Most studies consistently report elevations of the “neurotic triad” (hy20

pochondriasis, hysteria, and ression),r6 although recent work using a more sophisticated, ltivariate analysis has revealed a variety of separate subgroups in this population with less homogeneity than previously assumed. Blumer and Heilbronn,r5 utilizing an interview approach with 234 pain clinic patients, found uniformity in personality-limited ability to express emotions and a stoic, overly controlled quality. These findings support a similar notion of pain proneness originally promulgated by Engel in 1959.34 This work has been performed on patients who are already classified as chronic pain patients and have theoretically been enduring chronic pain for some time. The effect of pain on personality ay have been responsible for the uniformity of attributes whi In prospective stu udsley Personality Inventory, Lynn and Eyse am*’ were able to demonstrate that patients classified as introverts and neurotics bad lower tolerance for laboratory-induced pain. Other investigators failed to confirm these conclusi Using a model that reflects nt aspects of personality, Petrie’ 5 identified three types ividuals who theoretically differed from each other in t hich they processed sensory information. Petrie his blindfolded subjects blocks to feel and asked them to ate their size. He named subjects that tended to increase was perceived, augmentors, subjects that tended to decrease what was perceived, reducers, and the more accurate subjects, mo erates. When pain was subsequently induced in these i~d~~id~a~s in the laboratory, reducers tended to have the greatest tolerance for pain, while augmentors had the least. Petrie believes these processing styles are markers of broader personality attributes. In addition to personality styles and their potential significance regarding responses to pain, it appears as though one’s emotional state may strongly infhrence the degree of pain one tion to it. A classic example is anxiexperiences and one’s ety. Sternbach”’ in reviewed this literature and determined that anxiety has direct relationship to pain perception. This relationship has emonstrated both in individuals who are chronically anxious and in normal individuals in whom anxiety is induced. JohnsonG randomly prepared some patients for endoscopy while others were left unprepared and therefore were anxious regarding what would be done to them during the procedure. The better ~r~~ar~~, less anxious patients required less medication and reported less pain. Depression also has a role in pain perception. It has been associated with dramatically increased physical symptomatology, of which pain is a major somnolent. Patients who have recently sustained a loss and are grief stricken present: on average, witb four times the number of physical symptoms than matched con21

trols who have not recently sustained 10~s.~’ Finally, depression is a typical reaction to chronic pain,74 and that depression may, of itself, increase the perception of physical symptoms and potentiate the cycle of chronic pain.g1 DEVELOPMENT It has generally been assumed that the ability to perceive and experience pain increases as a child develops; accordingly, pain is less commonly considered a problem in children than in adults. For example, anecdotal analyses of typical clinical practice reveal limited use of anesthesia and analgesia in younger children as compared with adults who are undergoing similar procedures (bone marrow asI$ation, lumbar puncture, circumcision). Eland and Anderson report an enormous discrepancy in the prescription of analgesics by physicians for pain relief in children as compared with adults who have pain of similar origin. In one of the few articles for pediatricians on pain control in children, Swafford and Allan13’ wrote, “Pediatric patients seldom need medication for pain after general surgery. They tolerate discomfort well.” An examination of evidence and clinical practices reveals few controlled studies supporting such conclusions. A number of methodological problems are responsible for the limited published data in this area. The young child lacks ability to describe pain to adults, and therefore the entire area of pain experience, beyond its mere neurologic transmission, is extremely difficult to assess Although, as previously described, the distinction between the neurologic and psychological factors that are responsible for pain is artificial, nevertheless such a distinction will be made in an attempt to analyze the current literature on the developmental factors of pain in children. Neurologic Pain Transmission The developmental neurology of pain transmission has been studied, but its details remain unclear. McGraws2 described a continuum of infants’ reactions to pinpricks, ranging from essentially no reaction during the first week of life to diffuse body movements and crying by 1 week, to more immediate and intense reactions during the first month. By 3 months, she described more selective movements of the involved extremity without the mass movements that characterized earlier responses. Shirkey, quoted by Gross and Gardner,45 reported that a large amount of electrical stimulation was necessary to evoke a pain response on the first day of life, while by the third month, only half that amount was necessary. Regardless of the quantitative aspects of the stimulus, most authorities believe that newborns experience pain, and have disproved the old notion of 22

is necessary for a Flechsig’30 that complete myekinization quate neurologic functioning and therefore transmission of pain impulses. Further evidence t neonates experience pain comes from Gordon76 on pain-induced vocalizations, the work of Levine a which have a unique sound spectrograph pattern. This cry has been found in a number of primates as well as human infants and is different from the cry evoked by hunger, discomfort, or stress. In addition to these studies, however, most clinicians who have performed or witnessed a circumcision can testify to the newborn’s ability to ex erience pain. A recent study by Williamson and Williamson,14 LPcomparing babies who received a penile block prior to circumcision with those who did not, suggests that the amount of physiologic stress (as assessed by heart rate, Po2, respiratory rate, and crying time) is similar in nonanesthetized infants and in adults who are experiencing intolerable pain. They cite a study using the raze&on Neonatal Assessment 0% of infants who were circumScale which demonstrated that cised without anesthesia bad behavior changes detectable 3 weeks after surgery. Lombard et al.lrl speculate that the reason European and American studies differ in regard to gender differences in neonatal behavior may result from the fact that in American studies, which usually find gender differences, most of the male infants are circumcised. Other presumably neurologically based hypotheses exist that support our current practice of minimizing pain that we assume children experience. The younger children have a higher pain threshold an less pain than adults has been challenged by Has1 veloped a laboratory measure of pain using pressure on a. She found that younger children had a lower threshold for pain and therefore experienced pain more quickly than older children. Similarly, Jay et aL5’ found that children’s distress during procedures varied inversely with age. Using a variety of pain measures, they found that the level of distress in children under 7 was five times that of older children, and that there was a dramatic decrease in pain after age 7. Finally, children’s presumed inability to localize pain has been used to suggest that they do not experience pain as adults do. Eland and Anderson32 found, however, that 168 of 172 children aged 4-10 years who were asked to make an X on a body outline to indicate where they were experiencing pain could do so correctly. The notion that neonates, infants, and young children do not sense pain because of neurologic immaturity appears to have limited support in the existing literature, and although adequate methodologies have not been developed to test this notion definitively, the existing evidence suggests that virtually all children can and do sense 23

Pain Experience Children’s perception or experience of pain does appear to have more clearly developmental components, however. The experience of pain is more often associated with psychological variables than the primarily neurologic ones previously described. The ability to give meaning to the sensory input which has been triggered by tissue damage appears to be related to a child’s level of cognitive or intellectual development. Piaget, the seminal theoretician in childhood cognitive development, has suggested a predictable sequence of stages through which children acquire information about the world and eventually develop logical thinking. A major milestone in Piaget’s framework consists of the jump from preoperational, egocentric, rigid thinking, which characterizes most preschoolers, to thinking based on logic and hypothesis generation, which is more typical of schoolaged children. Investigators have discovered that children’s perception of illnesslo and pain12i parallels their cognitive development. Recent work by Beales et al7 highlights this point. These investigators interviewed 39 children (aged 6-17) with juvenile rheumatoid arthritis and divided them into two groups, a younger group (6-11 years) and an older one (12-17 years). There were no differences between the groups in regard to degree of inflammation or length of illness. Although all children described similar sensations in their joints, the older children uniformly attributed more unpleasant connotations to those sensations because the sensations “reminded them” of their potentially disabling illness, and they described these feelings as being more painful than the younger children did. Beales et al. interpreted this in light of the increased understanding and fearfulness that these older children had of what was happening inside their joints, and understanding the younger children did not have. When the younger children had surface wounds that were visible, however, and did not require abstract thinking to understand them, their reactions were like those of the older children. The work of Katz et al.“” and Jay et al.58 gives further credence to the importance of cognitive development in the experience of pain Both groups reported much greater “distress” during medical procedures in younger patients than in older ones. They reported a dramatic decrease in overt motoric distress at approximately age 7, which corresponds in Piagetian theory to the typical onset of concrete operational thinking. This increased sophistication in thinking allows children a more logical and realistic understanding of the need for performing the procedures, and these authors believe such knowledge is anxietyalleviating in the children and therefore the procedures cause them less distress. This parallels the findings of other investigators who have found that more anxious, less prepared adults experience more pain after surgery than those who were better 24

prepared and less anxious. hus, it appears that a child’s stage of cognitive development may determine, at least in part, the meaning or context of the pain, which has an important amplifying or dampening effect on the experience of a given painfm stimulus. In a slightly different vein, a number of authors45’ log, i2’ have described-the way children of different ages react psychologically to chronic pain due to burns Infants often withdraw, display sad faeies, exhibit eating and sleeping disturbances, and have difficulty establishing relationships. Preschoolers often become clingy, immobile, and may lose motor skills, verbal abilities, and sphincter control. They may experience nightmares, chronic anxiety, and panic. ecause of the limitations of their cognitive abilities, preschool s often do not ~understand reasons for their general discomfort or the need for painful medical procedures (e.g., dressing changes). There is often an implicit or explicit assumption that the pain is punishment for some previous wrongdoing. SC aged children often respond to chronic pain with increased essiveness, extreme shame (more quent in burn patien and nightmares, manifested by w drawal. Increased anxieiy is frequently seen and may relate to concern about loss of control and the potential reaction of peers. In adolescent patients, depression and extreme oppositional bebavior are common physiologic responses to chronic pain. Concerns about keeping up with peers and the significance of the pain on their future lives are overwhelming for many adolescents In summary, a number of common misconceptions have influenced our treatment of children in pain. It is clear that the neurologic transmission of pain messages occurs even in early infancy, although the exact experience of pain in that group remains vague. As children grow older, the sensations they experience become laden with meaning, wbieh has a modulating effect on the pain. Finally, children at different ages respond to pain differently, but the most typical responses are initial regression and later anxiety and depression

An appreciation of the variety of factors that contribute to t complexity of pain bas direct clinical implications. The amount of pain an individual experiences ha.s only limited correlation with the amount of tissue injury sustained. Of equal importance are a number of psychosocial variables-emotional state, personality, ethnic origin, context, and meaning of the pain to the patient. The clinician’s recognition of these factors should lea directly to intervention to ease the burden of the child’s pain. Adequate preparation of the child by thorough explanation, without jargon, has been shown to reduce anxiety and pain. Giv25

ing children and their parents realistic information about their illness and exploring with them its meaning also can create a less anxious, more comfortab1.e patient. Enlisting family and nursing support to diminish the boredom of hospitalization and to offer diversion and distraction from pain is helpful. Recognition and treatment of associated depression, anxiety, or personality aberration is also important. Efforts should be made to address the fears of younger children who are frightened of the unknown, concerned about separation from parents, and often cognitively unable to understand why they are being subjected to the trauma of hospitalizations and procedures. Such concern may mean the difference between a screaming, uncooperative child and a more compliant and comfortable one. Physicians should work to promote prolonged parental visiting, especially in children who are experiencing separation difficulties. Nursing and child life staff should have available a wide variety of developmentally appropriate play materials so that children can be diverted from their discomfort and can focus instead on more pleasant activities. Preparation of the child and the parent for procedures also is important, although some studies suggest that excessive preparation might heighten anxiety in some children. Accordingly, the amount of preparation a child receives should be individualized, depending on developmental stage and individual differences. Increased thought should be given to planning laboratory tests; obviously, and when possible, blood work should be consolidated. Most significantly, however, it must be recognized that children experience pain, and some routine attempts to detect it should be part of the treatment plan. Nursing and medical staff should be aware that children often do not request relief from their pain for a variety of reasons (fear of needles, lack of awareness that relief can be offered, lack of understanding of the word “pain”). A concerted effort should be made by staff to determine the extent of pain a young patient is experiencing. More specific treatment approaches to children’s pain will be made in the Treatment and Conclusion sections of this monograph. TREATMENT

FOR PAIN:

PHAR

ACOLOGlC

Those who do not feel pain seldom think

INTERVENTIONS

it is felt.

Samuel Johnson Despite the availability of a wide range of drugs for use in pain control, and general agreement that most pain could be eradicated with their judicious use, the treatment of severe pain is often inadequate.3 Parkesi” found that severe pain was present in 50% of the 276 adult cancer patients he investigated, and it remained unrelieved even in the terminal phases of their disease. Cartwright et al. 85 found that 87% of patients who died of 26

experienced unrelieved pain prior to death, while Marks and Sachar7’ reported that 73% of their patients undergoing treatment for pain continued to experience significant discomfort. The limited available data are even more striking for chil.dren. Eland33 evaluated the experience of 25 children, aged 4years, who were hospitalized for operation and found that 13 of the 25 were given no medication for pain relief during their entire hospital stay. For 21 of those 25, analgesics had been ordered p.r.n., but apparently the children were assumed not to be experiencing pain, because few medications were actually administered. Of the 12 children who did receive medication, the average was two doses per pita1 stay for problems such as spinal fusion, severe burns, nephreetomies. When Eland and Anderson3’ matched 18 of e children with 18 adults with similar diagnoses, they found that, while the children received a total of 24 doses of me ication, the adults received 372 narcotic analgesic doses and 299 nonnarcotic doses, a total of 671 medication doses. Well4 have recently refined that study, 10 years later, using a randomized sample of 90 adults and 90 children, matched for sex, with similar diagnoses (appendectomies, hernias, fractured femurs, and burns). Our data, though less striking, reveal that, depending on diagnostic category, adults receive between one-and-a-half and three times the number of doses of narcotics daily that children do. The reasons for undermedication are complex. Marks and Sawho evaluated 38 adult patients for char,78 two psychiatrists presumed overresponsiveness to pain, found that all of the patients had been given inadequate doses of analgesia. In an attempt to understand th henomenon, they surveyed 105 house officers and attending p sicians regarding attitudes toward and knowledge of analgesics. They found not only profound factual deficits, but also a grossly exaggerated fear of addiction in this group of physicians. Eland and Anderson3” detailed a number of myths which they feel are at the root of our reluctance to use adequate analgesics in children: children have immature nervous systems and therefore do not experience pain witb the intensity adults do; children recover quickly, which suggests they don’t need pain control; children will become addicted more easily than adults; children cannot localize pain and therefore probably do not experience it. Such myths maintain the status quo in which there appears to be a general reluctance to afford adults and, more strikingly, children complete pain relief. In this section, analgesics for mild and severe pain will be reviewed. Emphasis will be placed on the practical aspects of drug usage and on the problem of addiction. The interested reader is referred to ~~~affer~s’ for a detailed and practical de-

cancer

27

scription of the day-to-day problems encountered in pain management, and to Jaffe and Martin56 for comprehensive pharmacologic theory.

ANALGESICS FOR USE IN MILD TO MODERATE PAIN For the low-intensity pains of headache, myalgias, arthralgias, and other integumental structures, the antipyretic analgesics are clearly the drugs of choice (Table 1). These include primarily aspirin and acetaminophen, but other drugs will be mentioned. These drugs have a long history of therapeutic use with a high level of effectiveness, a low level of toxicity, and limited abuse potential. Aspirin and other antipyretic analgesics appear to work in part by inhibiting prostaglandin synthetase, which arrests the production of prostaglandins. Prostaglandins El and Ez are often released at the site of an injury, and they appear in some way to sensitize the nociceptors to histamine and bradykinin. Thus, the inhibition of local prostaglandin production desensitizes the nerve to chemical environmental factors that might ordinarily produce pain. Aspirin Aspirin is typically the standard against which the potency of other mild analgesics are measured. Salicylates have been used for centuries in preparations brewed from willow bark, but it was not until 1827 that Leroux identified its active ingredient, which he called salicin, named after the scientific name (Salix alba) of the tree from which it was isolated. Dreser introduced aspirin (acetylsalicylic acid) into the medical formulary in 1899. That preparation remains superior to any of the subsequently developed salicylates or combinations for pain relief.g0 Acetaminophen, which was developed later, has equal analgesic strength to aspirin, but, because it lacks anti-inflammatory properties, aspirin is a better drug for pain of inflammatory origin. Aspirin dosing for children is typically calculated at a dosage of 65 mg/kg/day, or 10 mgikgidose. It is available in chewable tablets and in chewing gum, but there is no adequate liquid preparation. Alka-Seltzer is, in fact, liquid aspirin but is not palatable to all children. Aspirin suppositories are available, but their absorption is unreliable and dependent on a number of variables, such as the amount of stool in the rectal ampulla. Although aspirin is an extremely safe drug, a note of caution regarding its use is imperative. Aspirin can cause gastrointestinal upset, bleeding, and ulceration. It decreases factor 7 levels and interferes with platelet aggregation. Altman and Schwartz1 have stated that “aspirin is absolutely contraindicated in any patient with thrombocytopenia, deficiency of any of the platelet coagulation factors, or any other condition compromising the he28

M

0.5-i

50 mg 5mg

Meperidine Oxycodone

0.75 0.08

mglkgldose mglkgldose

mglkgldose or 3 mglkglday 0.75 mgikgldose

PAIN*

SALIENTFEATURES

--~-________i_

Weak narcotic-narcotic agonist, high analgesic potential1 Narcotic, high analgesic potential? Narcotic, available as combination product with acetaminophen or aspirin

Nonnarcotic, anti-inflammatory No addiction or tolerance liability Similar to aspirin except for limited anti-inflammatory properties Weak narcotic, high analgesic potentjalI

FOR MILD

*“Equianalgesic doses” and “salient features” are from Noude B.W., in Bonica J.J., Ventafridda V. (eds.): Advances in Pain Research and Therapy. New York, Raven Press, 1979, p. 266, and used by permission” tAnalgesic potential refers to level of analgesia obtainable by increasing dose to point of limiting side effects.

30 mg

Pentazocine

Codeine

mg

10 mglkgldose

650 mg

Acetami~ophen 30--60

10 mglkgidose

650 mg

Aspirin

DRUG

PEDIATRIC DOSE

I.-DRUGS

EQUIANALGESIC DOSE

TABLE

mostasis mechanism.” In addition, the Committee on Infectious Diseases of the American Academy of Pediatrics28 has urged caution in the administration of aspirin to children who have influenza or varicella because of a possible association with Reye’s syndrome. Aspirin is rapidly absorbed in the stomach, as well as in the jejunum and duodenum. Salicylates may be found in the serum 15-30 minutes following ingestion, with peak levels occurring l--l% hours after ingestion. To minimize gastrointestinal upset, aspirin should be administered with milk or food. Drinking a large amount of water with an aspirin tablet is also helpful, as the more rapid the dissolution of the tablet, the less local gastrointestinal irritation will result. Aspirin has been mixed with a variety of different buffering compounds (aluminum hydroxide and magnesium hydroxide), but these do not reliably buffer aspirin as effectively as ingesting it with food, milk, or independently administered antacids. Enteric-coated aspirin is also available and may prevent some epigastric distress which occasionally accompanies salicylates, but absorption is often incomplete and slow, and the preparation is therefore less efficacious for use in acute pain. Salicylate ingestion is a common cause of poisoning in children and occasionally results in fatalities. Aspirin is available in fixed combinations with narcotic analgesics. Because aspirin acts peripherally and narcotics act centrally, the drugs in combination are more effective than either of the drugs given alone. Acetaminophen Acetaminophen (Tylenol and other brands) is an effective alternative to aspirin in patients who are aspirin-sensitive or have bleeding problems. It is approximately equal in potency to aspirin and does not have the associated gastrointestinal and hematologic problems of aspirin, or the association with Reye’s syndrome. Unfortunately, it also lacks the anti-inflammatory properties of aspirin as well, which makes it a less useful drug in patients with pain of an inflammatory origin. Acetaminophen is the active metabolite of phenacetin, in the family of paraminophenol derivatives. It was introduced by VonMering in 1893 but first became available in the United States in 1955. Acetaminophen is rapidly absorbed from the stomach and upper small bowel and achieves a peak level 3060 minutes after administration. A typical dose is similar to that of aspirin-65 mg/kg/day, or 10 mg/kg/dose. Side effects of acetaminophen are minimal at this dosage. Unlike phenacetin, a sister compound, acetaminophen has rarely been implicated in methemoglobinemia or hemolytic anemia. In overdosage, however, severe hepatoxicity can occur within 24-36 hours after ingestion. Acetaminophen is available in an elixir (160 mg/5 ml) and 30

drops (80 mgl0.8 ml). ration they are usin result in overdosage, result in lack of adeq

arents should be aware of which prepaon of drops for elixir could ion of elixir for drops could

Combination Drugs A large number of combination analgesics are available over the counter and are frequently promoted through the media as being more effective than single drugs. These preparations often contain aspirin or a~etami~o~hen, plus caffeine, buffers, antihistamines, phenacetin, or antispasmodics, Caffeine is typically added because of its mood-e ating effects, yet the amount of mg) is one-third to one-fifth that caffeine added (typically Xl-of a cup of coffee. Buffers such as aluminum kydroxide and magnesium hydroxide are similar to antacids and are thought to prevent the epigastric distress that occasionally accompanies aspirin administration. These buffered products, however, provide significantly less protection than taking aspirin with food or large amounts of water. Phenacetin included in some of the compounds has been implicated in analgesic nephropathy. Moertel et al.” compared a number of analgesic combinations with aspirin in 100 patients with mild to moderate pain. They demonstrated quite clearly that although the preparations were significantly more expensive t an generic aspirin, none provided the patient with more effective pain therapy, and some provided less. Most authorities agree that there is no available over-thecounter preparation approved for use in children which is more effective or has fewer side effects than aspirin or acetaminophen. Propoxyphene Propoxyphene (Darvon) is structurally similar to methadone and has been used as an analgesic for mild pain. Moertel’s previously cited work and the of others suggests it has little s considerably more expensive, or no efficacy over aspirin toxic, and likely to be abuse spite this evidence, Darvocet, a propoxyphene-acetaminophen combination, was the 12th most commonly prescribed drug in 1982.i3* A recent artiele4s has suggested that propoxyphene, because of its structural similarity to methadone, may aid in treating children who develop iatrogenie morphine dependence during a period of ventilator dependence. eatment of pain in children. It appears to have no role in the Nonsteroidal Anti-In~amm~to~y Over the past few years, a plethora of nonsteroidal anti-inflammatory agents have become available. Ibuprofen (Motrin), naproxen (Naprosyn), tolmetin (Tolectin), indomethacin (Indotin), sulindac (Clinoril), and nomepirac (Zomax) have been introduced primarily for treatment of osteoarthritis and rheumatoid arthritis. Many of these agents have significantly more anti-in31

flammatory properties than aspirin. Their analgesic usefulness appears limited to pain from inflammation of musculoskeletal origin. Many of these drugs have not been approved for use in children and they do not seem appropriate for use as a simple analgesic in children at the present time.66 Codeine Codeine is theoretically a narcotic and similar in pharmacology and structure to morphine. It is discussed here because of its usefulness in managing mild to moderate pain. Codeine is the drug of choice for moderate pain that cannot be relieved by antipyretic analgesics. Codeine is well absorbed orally and reaches a peak level in about l--l% hours after ingestion. Codeine has the highest parenteral to oral potency ratio of any opiate, being two-thirds as effective orally as parenterally, while morphine, for example, is one-sixth as effective orally as parenterally. The pediatric dosage of codeine is 3 mg/kg/24 hours in four to eight divided doses. It is available in pure preparations as well as in combinations with acetaminophen and aspirin at varying concentrations. The combination products allow more analgesia than is possible with codeine or aspirin or acetaminophen individually. Codeine has side effects similar to those of most narcoticsdrowsiness, lethargy, constipation, respiratory depression, and some risk of addiction. These side effects, however, are much less pronounced with codeine than with stronger narcotics. Codeine also has powerful antitussive activity and it is commonly used in cough preparations at a dosage one-half the analgesic dosage. ANALGESICS

FOR USE IN MODERATE

TO SEVERE

PAIN

Narcotic Analgesics If inadequate relief is obtained from the aspirin-like antipyretie analgesics, a narcotic or opioid analgesic should be considered. These remarkable drugs, which Osler called “God’s own medicine,“56 are grouped together because of similar properties of action, although many are structurally different from morphine, the patriarch of the family. The term narcotic has recently been challenged. The term was originally used to distinguish these analgesics from the antipyretic analgesics since they cause narcosis, from the Greek meaning stupor or benumbing. Narcotics act centrally, while aspirin and its analogues act peripherally. Jaffe and Martin56 have suggested that the term narcotic now be dropped from medical use because of its inexactness. Many of the narcotic analgesics do not cause stupor. Other authors suggest that the term opiate be used, but the relationship between some narcotics and opium is very distant. Jaffe 32

and Martin suggest use of the term opioid, denoting a functiona if not structural similarity to opium. Because of the continued common use of the word narcotic, however, we will use it interchangeably with opioid to describe this category of analgesics. An explosion of information regarding the opioids has occurred, following the discovery of opiate receptor sites and endogenous opiates. However, their use has been limited by fears of addiction, confusion regarding addiction and physical dependence, and concern about respiratory depression. In this section, the mechanism of action, ’ tric dosages, and particular characteristics of the major opioi s will be reviewed. Specific attention will be devoted to the problem of addiction. Opioid drugs are not interchangeable (Tables 2 and 3). They differ significantly in their parenteral to oral ratio (the amount of oral me ication required to produce analgesia equal to tbat achieve with a parenteral dose), length of action, and side effects. SW pharmacologic characteristics should be considered when selecting a drug from this category. Tolerance, Physical Dependence, and Addictive Botential of Narcotics There appears to be profo misunderstanding of a number of phenomena associated wi narcotic administration-tolerance, dependence, and addietion. Tolerance refers to a decrease in analgesic effect after repeated doses of an analgesic. Therefore, the dosage must be increased to maintain the same effect. Patients taking opioids develop tolerance to the analgesic, CNS, respiratory depressant, and euphoric effect of these agents. he constipating effects of opioids, unfortunately, do not typically lead to tolerance, and therefore are a relatively persistent phenomenon. Once tolerant, patients must take increasingly larger doses of medication (even beyond the lethal level in nontolerant individuals) merely to achieve pharmacologic effects. In one study, for example, rats, within 1 month, could survive five times a previously lethal dose of morphine. Similar data are now available in humans. Intermittent use of narcotics discourages the development of tolerance, and tolerance disappears once withdrawal from narcotics is completed. Therefore, if a patient who is taking a high dose of analgesics ceases taking those drugs and is subsequently given similarly high doses, fatal consequences could ensue. Tolerance is a physiologic phenomenon whose etiology is unclear, but as a concept it does not imply drug abuse or psychological weakness. The major misunderstanding in this area involves the confusion between physical dependence and addiction. Physical dependence is defined by Evansa as an altered physiologic state produced by the repeated administration of a drug which necessitates its continued use to p vent symptoms of withdrawal. Like tolerance, physical depe nee is a physiologic state. Al33

10 mg 1.5 mg 4mg 10 mg 75 mg from in Pain

*Doses and “Major differences Ventafridda V. (eds.): Advances p. 266, and used by permission.

morphine” Research

mg mg mg mg mg

PAIN*

1:6-15 1:5-6 1:3-6 1:2 1:3-4

PARENTERAL: ORAL RATIO

SEVERE

None Shorter Shorter Longer Shorter

J.J., 1979,

acting acting acting acting

MAJOR DIFFERENCE FROM MORPHINE

adapted from Houde R.W., in Bonica and Therapy. New York, Raven Press,

60 7.5 12 20 300

EQUIANALGESIC ORALDOSE

FOR MODERATETO

EQUIANALGESIC PARENTERAL DOSE

Z.-DRUGS

Morphine sulfate Hydromorphine (Dilaudid) Diamorphine (heroin) Methadone Meperidine

ORIGIN

TABLE

TABLE DRUG Morphine Methadone Meperidine Hydromorphine

3.--PEIXATRIG PARENTERAL 0.1 -0.2 0.1 -0.2 0.75 -2.0 0.015%.03

DOSING RANGE

mgikgldose mg!kg/dose mgikgidose mgikgidose

‘“Data derived primarily from extrapolations search. Effect may vary, and accordingly dose alized for each child.

RANGE* ORAL RANGE 0.5-1.2 0.2-0.4 1.0-3.0 .04-.08

mgikgldose mglkgldose mglkgidose mgikgldose

from adult reshould be individu-

though the exact etiology of cd dependence is not clear, nous opiates inhibit the proone hypothesis suggests that duction of endogenous opiates by a feedback loop, and when exogenous drugs are discontinued, an imbalance occurs because no endogenous opiates are being produced.g1 Physical dependence is a common phenomenon, and withdrawal symptoms occur in most patients who have taken narcotic analgesics for over 2 weeks and then cease taking them. Mild withdrawal symptoms, including restlessness, rhinorrhea, and sleeplessness, occur typically 8-12 hours after the last dose of narcotic. Peak withdrawal symptoms occur 48-72 hours after the last administered dose and may include irritability, tremor, anorexia, nausea, diarrhea, muscle pains, and dilated pupils. Dependence is easily controlled by a gradual tapering of medication and usually does not present a major problem for the clinician or the patient. The unfortunate equating of dependence and addiction has led to the underuse of narcotics. Tbe most commonly used definition of addiction is that of JaffeS7: ““Addiction is a behavioral pattern of drug use characterized by overwhelming involvement with the use of the drug (compulsive use), the securing of its supply, and the high tendency to relapse after withdrawal.” While dependence is common, addiction is an extremely rare phenomenon in patients entering the hospital for control of pain. Porter and Jieklo7 found only four addicted patients out of 11,000 wbo received narcotic preparations for pain in the hospital. In a related study, Miller and Jicks7 found an incidence of addiction of 0.09% in patients receivi meperidine. Twycross135 has described a low incidence of diction even in patients with terminal malignancies who t narcotics for prolonged periods of time. Despite these data, however, in the Marks and Sachar survey,7s 22% of physicians assumed addiction would occur in over 6% of hospitalized patients who received meperidine intramuscularly (IM) for pain control for 10 days. Newburger and Sallang’ make the poigna comment: “A child undertreated for pain, desperately and sin -mindedly awaiting his next dose of medication, comes closer to Jaffe’s definition of addiction than the properly treated patient at peace to pursue other concerns.” 35

Morphine Morphine, isolated in 1803 by Serturner and named after Morpheus, the Greek god of dreams, is the standard by which the analgesic properties of all opioid drugs are judged. It remains unsurpassed for pare&era1 use in patients experiencing severe pain. The exact mechanisms by which opioid drugs exert analgesia have not yet been untangled. The opioids appear to bind to receptor sites located primarily in the limbic system, hypothalamus, thalamus, striatum, and spinal cord. There they decrease the activity of adenylate cyclase and the intracellular concentration of cyclic AMP. Whether as a result of that mechanism or of some other, the opioids exert an influence on the release of neurotransmitters and inhibit release of acetylcholine, norepinephrine, substance P, and dopamine, and theoretically they dampen the influx of pain-producing messages to the CNS.56 In addition, morphine appears to alter a patient’s attitude toward pain-that is, to change the reaction to it. Even though patients still experience a sensation, it no longer is perceived as pain. The euphoriant action of morphine in individuals with pain is presumed to have a major role in pain relief. Another potential explanation for the analgesic activity of narcotics is their activation of paininhibiting pathways in the brain stem which exert descending pain control. Morphine has a number of physiologic effects. In the CNS, it produces a selective analgesia-i.e., without altering other senses such as vision, hearing, vibration. It may cause drowsiness, euphoria, and pupillary constriction, presumably due to excitation of the oculomotor nerve. The triad of pinpoint pupils, coma, and depressed respirations is pathognomonic for opiate poisoning. The nausea and vomiting that occasionally accompany morphine administration are caused by stimulation of the chemoreceptor trigger zone for emesis. Morphine has marked gastrointestinal effects. It decreases motility in the stomach and significantly slows the passage of gastric contents into the small bowel. It decreases propulsive movement, in the small and large bowel, constricts the ileocecal valve, increases the tone of the anal sphincter, and in general increases small and large bowel tone. All of these factors contribute to the marked constipation that often accompanies morphine administration. One of the most worrisome physiologic effects of morphine is respiratory depression. Therapeutic doses decrease respiratory rate, minute volume, and tidal volume. Respiratory depression presumably occurs because morphine reduces the responsiveness of the respiratory center in the brain stem to increases in Pcoz and thus decreases respiratory drive. Maximal respiratory depression occurs approximately 7 minutes following IV admin36

i&ration, 30 minutes following I administration, and 90 minutes following subcutaneous SC) administration. The kinetics of morphine in children have recently been described. Dahlstrom and colleaguesso found that the minim morphine concentration in plasma necessary to suppress clinical signs of pain during surgery was 65 rig/ml. Using t minimum effective plasma levels, there was no difference between children of different ages and their sensitivity to morphine. The morphine level in blood peaks at 30 minutes after IM or SC administration, and almost immediately after IV administration. Its half-life is usually assumed to be approximately 2 hours, yet Kaiko63 found si nifieant variation in the mean ration of action of morphine from 2.5 to 4.2 hours, depending on age and dosage. Others have ested a half-life of up to I6 hours.12” This suggests the nee adjust the dosing schedule of morphine to the needs of the patient. Although morphine is ~r~rn~t~y absorbed after pare&era1 administration, its oral absorption is poor. The oral dose of morphine is approximately 6-15 times higher than the equivalent parenteral dose. Side effects also increase with the increased dosage, and the usefulness of oral morphine is limited. The pediatric dose of morphine sulfate is 0.1-0.2 mg/kg/dose every 4 hours. Morphine is usually given SC or IM. These routes require repeated injections, which may frighten the child and exacerbate bleeding diatheses. slow push (4-5 minutes) administration has been attempte the past, but often results in dramatic fluctuations in in control. Miser and colleagues88, so have described both a c inuous IV infusion of morphine for children in pain with terminal malignancy and a continuous SC infusion using a syringe pump. The advantage of a continuous SC infusion is that an IV line is not required and children can be sent home with a pump syringe in place. Morphine sulfate dosages for the continuous IV route range from 0.025 to 2.6 mg/ kg/hour, with a median dosage of 0.04-0.07 mglkgihour. For SC administration, the dosage range is 0.025-1.79 mgikgihour, with a median dosage of 0.06 mgkghour. Meperidine Meperidine was synthesize by Eisleb and Schaumann in 1939. Its analgesic effect is similar to that of morphine, although it is biochemically quite diffe Meperidine differs from mo ne in several ways. It pr ces analgesia more quickly, usu ithin 10 minutes after SC administration, and its duration of action is shorter. I”;f equianalgesic doses to morphine, it has less spasmogenic effects on the biliary tract and is preferable to morphine for children with biliary tract disease. Its major distinction from morphine, however, is its better oral absorption. The parenteral to oral ra-

tio with meperidine is lower than with morphine (1: 4 vs. 1: 6). A caution has been raised with the use of meperidine in patients with sickle cell disease and renal failure, as it is reported to have induced seizures.l15 The mechanism is presumed to be based on the accumulation of normeperidine, an active metabolite which has CNS excitatory effects. The recommended pediatric parenteral dosage of meperidine is l-l% mgikgidose, or approximately 6 mg/kg/24 hours, given in four to six doses. Methadone Methadone has a number of unique properties that distinguish it from morphine. It is highly recommended in oral form for relief of moderate to severe pain.. It is well absorbed from the gastrointestinal tract and has a parenteral to oral ratio of 1:2, making it the most efficacious orally administered potent narcotic. It has a longer duration of action than morphine and causes less sedation, less euphoria, and fewer changes in heart rate. It rarely produces nausea or vomiting. Tolerance to methadone develops more slowly than to meperidine. Methadone can suppress heroin withdrawal symptoms and so is often used for maintenance in heroin-addicted individuals. It allows an individual to function without the euphoriant and sedative effects of heroin, and it prevents the physiologic withdrawal symptoms. Methadone is now a frequent component of a number of “cocktails”-narcotic oral drug mixtures used to relieve chronic pain in cancer patients. The risk of potential methadone accumulation has been suggested, and therefore patients should be monitored carefully for side effects. The pediatric dose of oral met,hadone is 0.2-0.4 mg/kg/dose, or 0.7 mglkgi24 hours. Pentazocine Unlike the narcotics discussed above, which are opiate agonists, pentazocine (Talwin) is both an agonist and antagonist. Pentazocine was introduced initially as an analgesic because it was thought to have lower abuse potential than other available drugs. However, addiction to and abuse of pentazocine has been reported. Pentazocine is not approved for children under 12, has significant CNS effect, and has significant abuse potential. Its role in the control of pain in pediatric patients is extremely limited. Pentazocine has antagonistic properties, and its side effects are somewhat different from those of the other opioids. They include sweating, dizziness, anxiety, nightmares, and hallucinations, properties which make it an unattractive drug for use with children. Oral Narcotic Mixtures Oral narcotics have been combined with an assortment of other ingredients in attempts to amplify analgesia and dampen 38

noxious side effects. The most well-known of these cocktails was developed at Brompton ospital in England and initially congin., and honey. “Brompton cocktail” tained morphine, cocain has become the generic name for a number of different analgesic mixtures which now typically contain morphine, cocaine, and alcohol. Additional mixtures ‘have surfaced, developed in large measure by the growing ho ce movement, and aimed at providing both comfort and me 1 clarity to individuals with terminal illness. The hospice mixtures have added phenothiazines to potentiate the analgesic effects of morphine, relieve anxiety, and provide control of vomiting. It has been reported, however, e mixtures often causes dysthat the cocaine in Brom phoria, and the alcohol is sant for children to drink. Accordingly, Newburger and ‘i report that they prefer combining longer acting, absorbed methadone with amphetamines to offset th g effects of the narcotic. What is important, however, is tailoring medications to the specific needs of an individual patient. If anxiety is a major factor, phenothiazines might be considered; if the patient appears overly sedated, amphetamines might be considered; if longer action is required, methadone should be considered; if rapid action is required, shorter acting cotics could be considered. ore gs are presented next. details on these adjunctive ADJUNCTIVE DRUGS A number of additional drugs have been found to have a role in the treatment of pain patients (Table 4). These drugs may help relieve pain by (1) elevating mood or reducing anxiety in the patient, (2) potentiating narcotic analgesia, and (3) exerting a primary analgesic effect of their own. Increasingly, combinations of drugs are being used as the mainstay of pain therapy. Antidepressants The tricyclic antidepressants, imipramine hydrochloride and amitryptiline hydrochloride, have a distinct role in pain therapy. They have proved effective in alleviating reactive depression in patients with chronic pain. This is not the sole explanation for the analgesic effects of antidepressants. A number of clinical studies have shown, for example, that despite obvious evidence of depression in only PO% of patients receiving antidepressants, 45% of patients receivingxt;ricyclic medications alone reported sizfSnificantly reduced pain. Recent work by Botney and Fields suggests that amitryptiline increases morphine analgesia by blocking serotonin. uptake in the terminals of monoaminergic neurons. The rise in serotonin potentiates the effectiveness of the serotonin-dependent descending intrinsic analgesia system which connects the periaqueductal gray area indirectly to the dorsal orn of the spinal cord. Thus, the tri3s

2-5

Imipramine, Amitryptiline,

Sedation Improved sleeping Antidepressant activity Additional analgesia

Tricyclic

antidepressants

Dextroamphetamine,

Decrease respiratory depression Decrease drowsiness Additional analgesia

(?)

DRUGS,

DRUGS DOSAGE

2-5

mglkglday mgikgiday

2-10

mg/day

Chlorpromazine, 2 mgikgiday Perphenazine, .l-.2 mgikgidose, to 8 mgi8 hr Fluphenazine, .02-.05/mg/kg/dose, to 1 mg/S hr Haloperidol, .05-.075 mgikg/day Hydroxyzine, .2-.5 mg/kg/day

SPECIFIC

Stimulants

analgesia

of anxiety

USES

Reduction Antiemetic Additional

CLINICAL

4.-ADJUNCTWE

Major tranquilizers/ antiemetics

CATEGORY

TABLE

in children

Urinary retention Respiratory depression Use with caution in patients with cardiac or renal abnormalities

Tremulousness Palpitations Tachycardia

Extrapyramidal Increased dystonia Anticholinergic

SIDE EFFECTS

eyclics appear to have a direct effect on the CNS that allows morphine to be more effective. An additional benefit of the tricyclics may be due to their sedating effect, which improves sleep in pain patients who ty ically display altered sleep cycles. Antidepressants exert so analgesic effect by day 10 of thera and some antidepressant effect by day 14. They are appropriate only for individuals who can expect prolonged pain. There has been limited research on the effectiveness of antidepressants in children in general, and no research on the effectiveness of antidepressants on children in pain. The drugs are not recommended for children under 6 years of age. For older children, the dosage of imipramine and amitryptiline is typically 2-5 mg/kg/day, usually 25-108 mg/day. It has been suggested that the dosage be started at 1 mgikgiday and gradually increased over a period of 2 wee s.ii* The drugs should be administered at bedtime to help wit sleep and decrease the sedating effects. Patients may expect dry mouth and drowsiness for the first 5 days. The anticholinergic effects often cause urinary retention and constipation, and they can potentiate the respiratory depression of narcotics. The drugs should not be administered in conjunction with MAO i bitors as their interaction can produce convulsions and occasionally coma. Antidepressants should be used with caution in patients with known cardiac or renal abnormalities. Major Tranquilizers The phenothiazines and butyrophenones have also been used as adjuncts in pain therapy but must be used cautiously. They are typically given to reduce the anxiety that occasionally accompanies pain, particularly cancer pain. In addition, they have antiemetic properties that are helpful in controlling the vomiting associated with narcotic administration. Finally, some phenothiazines (e.g., chlorpromazine? have analgesic properties in their own right. Major questions have been raised regarding the use of phenothiazines in pain control. The phenothiazines produce sedation, can aggravate respiratory depression, cause orthostatic hypotension, and occasionally produce disabling extrapyramidal side effects. hIany phenothiazines are antianalgesic (promethazine, prochlorperazine, and t~i~~o~erazi~e~ and can, in fact, increase pain perception. Nevertheless, a number of authoritiesz3’ il’ still maintain that phenothiazi s can potentiate the analgesia obtained through morphine. alpern and 130nica,46 for example, report that 10-E mg of lorpromazine administered three times a day can reduce by one-half to two-thirds the dosage of narcotics that is necessary. Some phenothiazines may be viewed as adjuncts to narcotic therapy in certain patients, but the literature remains controve ial. If phenothiazines are being considered, chlorpromazine mgikglday), perphenazine (0.1-0.2 47

mgkgidose to 8 mgidose every 8 hours), and fluphenazine (0.020.05 mg/kg/dose to 1 mgldose every 8 hours) are the drugs of choice. Haloperidol, a butyrophenone and a major tranquilizer, can offer analgesia independently and is particularly effective when administered in conjunction with an antidepressant. Kocher7’ suggests that using haloperidol and an antidepressant offered partial relief or reduction of narcotic dosage in 60%~80% of the patients he evaluated. Shimm et al.ll’ also report marked success with haloperidol using a nighttime dose, which minimizes risks of extrapyramidal side effects and sedation. They suggest that the use of haloperidol may permit decreased narcotic administration and freedom from some of the inherent narcotic risks. An anticholinergic drug such as benzotropine mesylate (Cogentin) may be used to diminish extrapyramidal symptoms in individuals receiving these drugs for protracted periods. Minor Tranquilizers A number of minor tranquilizers have been used to control pain. Although anxiety clearly has a role in escalating pain perception, and one would therefore assume that anxiolytic drugs might be helpful, the antianxiety drugs have had limited success. The depression and occasional disinhibition associated with their administration have limited their usefulness. The benzodiazepams, for example, have little role to play in pain control. Hydroxyzine, a sedative antihistamine, may be useful through sedation or through direct analgesic action. In a study of postoperative adult patientsa 100 mg of hydroxyzine given IM was found to be particularly effective in pain control and to be the equivalent of 8 mg of IM morphine. The role of hydroxyzine in pain control requires further study, but present data are promising. The typical dosage of hydroxyzine in children is 2 mg/kg/ day given orally, divided into four doses. Amphetamines Amphetamines have also been used in the management of chronic pain. Forrest et a1.40 concluded that 5 mg of amphetamine could double the effectiveness of morphine, in addition to increasing respiratory rate and decreasing drowsiness. Amphetamines may have independent analgesic properties as well. Newburger and Sallang report using amphetamine with methadone instead of the Brompton cocktail for control of chronic pain in children. GENERAL APPROACHTO ANALGESIC USE A number of general principles have emerged as physicians have become increasingly sophisticated with analgesic and adjunctive drugs for pain control. These are discussed below. 42

Preventative Approach Perhaps the most vital clinical information that has eme from the pain control literature is the importance of the ventative approach to pain. The literature clearly demonstrates that pain medication should be prescribed in anticipation of pain and to prevent its recurrence, rather than to eliminate the pain once it has occurred. That is, medication should be administered regularly and prophylactically in a time-contingent manner. Prescribing pain medication on a p.r.n. basis requires the patient to experience pain before getting relief, which is both physiologically unsound (higher doses of narcotics are necessary to abort existin pain than to prevent its recurrence) and inhumane. Angel1 %has written about p.r.n. pain administration: “We are left then with the image of a patient who can anticipate severe pain toward the end of each 3- to 4-hour period, who counts the minutes until the end of the interval, and desperately hopes that a nurse will be nearby and promptly give him his dose of narcotics when it is time. To such a patient, the medical profession’s attention to pain must seem confined to limiting relief from it.” It is clear that the p.r.n. approach to pain control has a limited role in current practice. Choice of Drugs The choice of analgesics shoul be tailored to the needs of the child. The goal is to prevent eradicate the pain the patient is experiencing, not how mue e assumes he is experiencing. For mild to moderate pai irin or aeetaminophen should be considered. For slightly more severe pain, aspirin or acetaminophen with codeine are good choices. If these are inadequate for the patient’s needs, or if e side effects of codeine prevent administration of adequate ses, parenteral morphine is the d oral methadone is the drug of drug of choice for acute pain choice for chronic or prolon ain. If depression is a problem for the patient, or if he is having difficulty sleeping, a tricyclic antidepressant should be added. If marked anxiety and/or nausea and vomiting are present, one of the phenothiazines with analgesic activity may be helpful. If oversedation is a problem, reduction in dosage or addition of an amphetamine may be indicated. Dosage Although debate exists as to whether to start low and increase the dosage or start high and d rease it, the literature appea to support the latter view. If ain is immediately controlle even at the risk of some sedation, the patient’s anxiety will often dramatically diminish as he or she realizes that the pain will not necessarily be a continuous part of life. Angel13 suggests a flexible dosing regimen whereby the patient is asked at fixed intervals whether relief from pain is needed and is given a 43

choice of a small or a large dose of medication. This approach elevates patients from positions of supplication and gives them some control over their medication, which may have positive psychological benefits as they cope with illness and pain. Flexible dosing may be appropriate for older children, although clearly very young children are not capable of such decisions. Route of Administration For other than acute pain, the oral route is preferable to the parenteral one. Children will often fail to report pain or deny its existence in order to avoid receiving an IM injection. Therefore, if parenteral drugs are necessary, an IV route should be strongly considered, either through a slow push or a continuous infusion method. Side Efiects CoNsTIPATION.-Narcotics can be extremely constipating. Prophylactic laxatives that increase peristalsis should be administered in conjunction with narcotic therapy. RESPIRATORY DEpREssroN.-Respiratory depression is a potentially fatal consequence of narcotic administration. The physician and nurse should be aware of the peak times of its occurrence, which varies with method of administration, and should have naloxone located by the bedside when IV administration is used. The pediatric dosage of naloxone is 0.01 mg/kg, IV, IM, or SC. Doses can be repeated every 2-3 minutes. Because naloxone has a short half-life, the patient should be monitored carefully for reemergence of symptoms. Monitoring Pain Control A high index of suspicion is necessary to determine if children are in pain. They may deny pain for fear of receiving a parenteral response to their complaint, or they may not understand what the physician or nurse is asking them. Those caring for children who may be in pain should be aware of the physiologic alterations that accompany pain (increased heart rate, increased respiratory rate, increased blood pressure, increased palmar sweating) and not rely solely on children’s complaints or reports. It should be assumed that if a procedure or surgery causes pain in adults, it causes pain in children as well. Psychological Support The child’s worries, concerns, and fears may have a substantial impact on pain perception, and these should be addressed as openly as is possible. The following section outlines some nonpharmacologic approaches to pain management.

44

SURGERY Through the years, a r of neurosurgical procedures have been attempted on p with pain in order to interrupt the transmission of pain messages through the nervous system. Ablation of the presumed pain pathways has been attempted in at least 15 sites in the CWS.“g For the most part, these procedures have not lived up to initial expectations because of the marked complexity of pain transmission, in which a number of alternative pathways come into play once one is eliminated. In addition, new but equally i~~a~a~itating pains may arise from the sensory depriv rgery, triggering spontaneous discharges Peripheral nerve OF alcohol are the simplest procedures att omy, the destruction of the nerve root, has longer lasting results than peripheral nerve blocks, particularly in the trunk, upper limb, and shoulder areas. These results, however, are seen only in patients who have a short survival time, as pain typically recurs within 4 months. A~tero~ateral cordotomy, or spinothalamic tractotomy, has been the most common procedure attempted. In this procedu.re the spinothalamic tract is obliterated at one of a number of different sites in the cord and/or at the medullary or mesencephalic levels. These procedures can be performed in an open manner, in whi.ch the cord is visualized, or percutaneously. The closed percutaneous procedure has the advantage of baving minimal surgical morbidity and can therefore be performed on patients who have been markedly debilitated by cancer or its treatment. About 60%~80% of patients experience some relief following these procedures, but pain returns in 30%~50% within 3 months. Finally, a number of intraeerebral procedures have been attempted as a last resort ontrol pain. Xtereotactic thalamotomy has been attempte and although initial pain relief is achieved, pain returns in o/o-80% of patients within weeks to months following the pro re. Lobotomies have also been performed for pain relief in ttempt to alter the anticipation of pain, its memory, and the individual’s affective response to it. The personality changes that accompany this procedure make it an untenable alternative. Cingulotomy was introduced in the 1960s as an attempt to relieve pain while protecting the individual’s psychological fu~~t~Q~~~~. Although the duration of pain relief is limited with this procedure compared to lobotomies, mental clarity is of ablative neurosurgical procedures In summary, a have been devel.oped in an attempt to control pain. Most of these are treatments of last resort and should be reserved for patients 45

with cancer who have short survival potential, a localized lesion causing pain, and who can tolerate the anesthesia typically required. TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION The use of cutaneous stimulation to relieve pain is common and done by most of us almost reflexively. Pain relief with massage and hot or cold compresses may last only as long as the treatment persists, or there may be residual relief after the conclusion of treatment. The exact explanation of pain relief with these methods is unclear. Using the gate theory, however, we might postulate that the larger diameter, lower threshold nerves are being recruited, and these may shut down the gate to messages from the small-diameter nociceptor fibers and therefore decrease the pain messages that are sent to the CNS. A number of other explanations, including increased endorphin release, have been postulated. Expanding on simple cutaneous stimulation Shealy118 reported that transcutaneous electrical nerve stimulation (TENS) applied near the painful lesions or on nerves that innervate them provided significant relief. Shealy’s work and that of others provided the framework for use of TENS, which is now a commonly used modality for many pain problems. Its use can decrease or eliminate the need for narcotic analgesics. The stimulator is typically a battery operated device which applies a mild electric current to the skin and, presumably, the stimulation of large type A fibers competes with the pain message and diminishes pain perception (Fig 4). A variety of different models of stimulators are available and most can be worn all day or just a portion of the day and appear to have limited side effects. Plethysmographic studies also suggest increased blood flow to the area being stimulated. Although TENS was initially used primarily for chronic low

Fig 4.-A Zimmer, Inc. 46

transcutaneous Reproduced

electrical by permission.)

nerve

stimulation

(TENS)

unit.

(Courtesy

of

back pain in adults, it has now been used on arthritic extremities, for headache and for postoperative incisional pain.‘15 Epstein and Harris35 have reported their experience using TENS in children with chronic pain following traumatic surgery. They report that 60% oft e children they have treated in Hopkins have required no ada pediatric pain center at Joh ditional treatment other than a TENS unit for use at home and at school. A further modification of TENS has been the implantation of electrodes into the dorsal column to provide continuous stimulation directly within the nervous system. This approach, with its obvious risk of infection, should be reserved for use after more conventional approaches ave proved unsatisfactory. TENS remains a tool with enormous potential. Shealy suggests it as the treatment of first choice, even before pharmacologic treatments. McCafferysl suggests it might be an appropriate modality to use in children in the immediate postoperative period since it lacks the more noxious side effects of narcotics and prevents ileus and atelectasis because of the patient’s increased comfort. TENS a tool with which pediatric centers should become acquaint HYPNOSIS

AND

RELAXATION

The usefulness of certain noninvasive techniques for pain control has become increasingly obvious over the past few years with the increasing interest in behavioral medicine. While techniques such as distracting a chil from pain by diverting attention to other thoughts or attempting to promote relaxation have always been used by parents and physicians intuitively, the value of such techniques had not been recognized, nor had they become a routine part of the care of someone in pain until recently. There is significant overlap between the types of these approaches, as well as much definitional confusion. The interested clinician would do well to read articles by McCaffery’l and Gardner and Olness42 on the subject or to attend the short courses offered in these techniques by the American Society of Clinical Hypnosis or the Society for Clinical and Experimental Hypnosis. Hypnosis Hypnosis suffers from a glut of definitions, each of which reveals fundamental philosophical differences in the practitioners who espouse them. McCafferysi highlights the problem by quoting Crosbeck and Hill, who offer lists of definitions of hypnosis based on their review of the world’s literature: uncritical acceptance of ideas, heightened suggestibility, altered consciousness, selected wakefulness, intensified attention and receptiveness, intensive concentration, and many others 47

Zeltzer and LeBaron14” offer a practical distinction. In attempting to quantify hypnotic versus nonhypnotic techniques for pain relief in children with cancer, they suggest that their hypnotic group was the one in which the therapists helped patients become involved in pleasant images or fantasies, while the nonhypnotic group was merely distracted from pain by the therapists. The use of guided imagery and fantasy would appear to differentiate hypnotic from nonhypnotic techniques in Zeltzer’s scheme. The specific hypnotic approach used should be determined by the developmental age of the child and the comfort of the therapist. A number of useful suggestions are offered by Gardner and Olness4’: (1) direct suggestion, such as “imagine painting numbing medicine on the part of your body that hurts”; “imagine injecting an anesthetic into that part of your body-feel it flow in and feel the numbness it produces;” “pretend there is a switchbox in your arm and you can turn off the switch that connects the pain to your brain”; (2) distancing suggestions“imagine that the painful limb doesn’t belong to you”; “imagine you are in a favorite comfortable place”; “listen to the ocean, smell the air, look at the trees, etc.“; and (3) suggestions for feelings that are antithetical to pain-“think of the funniest movie you ever saw.” With such techniques, the child can be guided away from the obsession and panic a painful procedure might produce to a more pleasant and nonthreatening thought. Zeltzer and LeBaron146 demonstrated a significant reduction of pain and anxiety in children undergoing bone marrow aspiration and lumbar puncture with the use of hypnotic approaches. They found that some of the nonhypnotic diversionary approaches also were successful, but less so than the approaches that involved fantasy. They suggest that such techniques can be used by any health professional working with children, and the only prerequisites are creativity and interest, not specialized training. T~;s~~~rature on hypnotherapy and pain control is growing, ’ and although definitive studies of effectiveness are not yet available, the noninvasiveness, limited cost, and fundamental humaneness of this approach suggest it be attempted in institutions that care for children in pain. Relaxation Relaxation may be defined as a state of freedom from anxiety and tension, both physiologic (e.g., muscle tension) and psychologica181 A state of relaxation is antithetical to anxiety and helps reduce that frequent component of pain. Relaxation techniques can divert attention away from pain and decrease the skeletal muscle tension that often accompanies chronic pain. Relaxation can combat fatigue and facilitate sleep. Benson and co-

workersl” I3 have described d physiologic relaxation response which theoretically diminishes the unhealthy effects of stress on the individual. There are multiple avenues to achieving a state of relaxation-we all relax an achieve comfort in different ways, depending on upbringing, ulture, and physiology. Three standardized methods of relaxation (meditation, progressive relaxation, and biofeedback) knave been studied. MEDITATION.-Meditation is focusing on a single thought. In the relaxation literature, meditation typically entails focusing attention on breathing and following the air as it courses through the lungs and is expelled. In other systems, such as transcendental meditation, a single word or thought may be the object of focus and an attempt is made to exclude all else from one’s consciousness. Eventually, it is thou ht, such focused activity yields a more relaxed state. Benson, 73 a cardiologist, has analyzed the physiologic correlates of transcendental meditation and described what he calls the relaxation response. Gardner and Olness4’ suggest the specific use of such a technique in pain control in children by telling them to concentrate on their breathing and follow its course. PROGRESSIVE RELAXATION EXERCISES.-Another t achieving a relaxed state is known as progressive re was developed by Jacobson55 in 1938. It has subsequen modified for children and even for children with special needs.‘” This technique involves the sequential tensing and releasing of a specific pattern of muscles. Theoretically, by tightening the muscles and then releasing them, more relaxation can be achieved than by merely relaxing, A drawback of this approach is the length of time require to learn the technique and the amount of time daily that be devoted to practicing it. Jay et a1.60 have developed a b oral “package” of breathing exercises, imagery, and rehe strategies to help children undergoing painful medical procedures. They report at least a 40% reduction of distress in all but one of the ten children involved in the research. BIOFEEDBACK.-Biofeedback, as defined by Stern and Ray,127 is the use of monitoring instruments to detect and amplify internal physiologic processes in order to make this ordinarily unavailable information available to the individual. Typically the individual is taught to manipulate the displayed signals that arise from areas often presume to be out of an individual’s control. The patient and therapist nitor muscle tension through a modified electromyogram (E ) and attempt to reduce muscle tension and promote relaxation. Bn addition to the benefits of relaxation, biofeedback can often promote a feeling of mastery 49

over bodily phenomena, which may generalize to a feeling of mastery over pain. Biofeedback has an advantage over other forms of relaxation in its rapid ability to allow relaxation, sometimes within 20 minutes of the first session. Its disadvantage is in the requirement for relatively expensive machinery. Although this use of biofeedback is in its early stages, literature is developing on its help in pain problems in children, particularly in the area of headache control. Mehegan et aLs3 studied the effect of nine sessions of EMG biofeedback of facial muscle tension on the headache frequency in 20 children, aged 7-12 years, who had had headaches for an average of 2.7 years. For all children, the headache activity (intensity x duration) decreased from a baseline level of 33.5 to a final level of 2.5 in week 20. Headache hours fell dramatically, as did the use of medication. Fentress and Masek37 modified this work by introducing a progressive relaxation group. They found that relaxation was also extremely successful at decreasing headache frequency and intensity. Further replication of this work is necessary, but it appears that behavioral medicine approaches may be extremely effective at controlling certain types of pain in childhood.7g SPECIFIC PAIN PROBLEMS

IN CHILDREN

Although injury and physical illness cause pain in both children and adults, there are some significant age-specific differences in the types of problems that present as pain. For example, children rarely develop low back pain, a leading cause of chronic pain in adults and the major diagnostic group seen in most pain clinics. On the other hand, children are more likely to experience significant distress during medical procedures and to experience recurring patterns of nonorganic pain. The following section explores the unique aspects of a variety of different acute and chronic pain problems in children. Detailed discussion of these entities is beyond the scope of this monograph, and more extensive reviews are referenced for the interested reader. PAIN

ASSOCIATED

WITH

MEDICAL

PROCEDURES

In children, anxiety produced by the anticipation and performance of medical procedures is so clearly intertwined with perceived pain that Katz et a1.65 and Jay et a1.58 have combined these variables into a single construct: distress. A small literature on children’s distress related to medical procedures is available. Most of the studies have examined children with chronic illness, particularly cancer, who are subjected to repeated medical procedures, including bone marrow aspiration and lumbar puncture. 50

Zeltzer and LeBaron14G used a visual analogue scale to determine if hypnotic and relaxation therapies were effective in alleviating pain. They asked 45 oncology patients, aged 6 through 17 years, to rate the pain they experienced during lumbar puncture and bone marrow aspiration on a scale of 1 (no pain) to 5 (maximum pain). The youngsters reported an average pain rating of 4.42 and anxiety rating of 3.97 for bone marrow procedures, and an average pain raking of 3.89 and anxiety rating of 3.82 for lumbar punctures. “Ibis study supports the inextricable relationship of pain and anxiety in this population of children and suggests that these relatively common procedures may be an enormous source of discomfort. Katz et a1.,e5 in a similar group of patients, determined that anxiety was inversely related to age: the younger the child, the more marked and demonstrative the anxiety and distress. Older children demonstrated fewer overt (screaming, kicking, etc.) signs of distress. These authors also found that in the pediatric cancer population, distress was not decreased by frequent visits, as it is in children with other chronic diseases. Jay et a1.58 reported similar findings. Age was the strongest predictor of distress during bone marrow aspirations, and younger children’s distress was more overt. They found that distress levels in younger children were five times those of older children. They also found a dramatic decrease of istress at ages 6-7, a time when, according to Piagetian tbeor children should be more able to understand the need for these procedures. In contrast to Katz et al., they found a decrease in anxiety with subsequent procedures. It should be noted that even though older children appeared to demonstrate less overt distress on self-reporting measures, they revealed significant anxiety and worry about the procedures they were to undergo. Investigators have attempted to relate maternal or parental anxiety to the child’s distr Most studies suggest a clear relationship between increas maternal anxiety and increased distress in the child.58 In general, parents who were anxious and anticipated high levels of distress in their child had children who were more distressed.137 have questioned whether the A number of investigatorsii7 presence of parents affected the child’s comfort level during a procedure. Results from these studies are contradictory. It appears that the child’s age, parental anxiety, and the child’s temperament must be taken into account. Generally, then, it appears that younger children have more overt agitation than older children, but it is clear that medical procedures evoke significant fear and anxiety in all children who are subjected to them repeatedly. It appears that the amount of distress a child experiences correlates to some extent with developmental age: the more sophisticated the child’s cognitive development, the less anxiety he or she may experience. 51

CANCER Two unique aspects of cancer pain in children have been identified by Jay and Elliott.” Children typically develop different cancers than adults, and these cancers are less likely to cause pain. The most frequent cancers in adults-breast, lung and bowel cancers-have a high incidence of associated pain. The most common cancer in children, however, is leukemia, accounting for 40% of childhood malignancies. Leukemia has a low incidence of tumor-related side effects, and even those are rarely present in remission, which is becoming increasingly common in leukemic children. A second unique aspect of childhood cancer is that in most younger children the term “cancer” is devoid of the death-knell connotation which most adults and adolescents bring to it. While this may have unfortunate consequences during procedures when children are unable to understand why they must be subjected to pain, it has potentially positive ramifications regarding children’s understanding of their disease and provides them some protection from the massive psychological effects and implications of the diagnosis of cancer. The pain induced by cancer has a number of origins. Foley3’ evaluated the causes of pain in 120 adult cancer patients and found that 62% had symptoms secondary to direct tumor involvement, 31% had symptoms secondary to treatment (16% post surgery, 11% post chemotherapy, 4% post radiation) and 5%-7% had symptoms of unclear etiology. Altman and Schwartz’ suggest that the pain secondary to tumor has six possible mechanisms: (1) compression of a nerve by tumor or adjacent bone fracture, (2) perivascular or perineural lymphangitis secondary to infiltration of blood vessels or nerve by tumor, (3) partial or complete occlusion of blood vessels with secondary venous or arterial ischemia, (4) infiltration to tissues tightly enclosed by pain-sensitive structures, (5) necrosis, infection, or inflammation of pain-sensitive structures, and (6) obstruction of a hollow viscus. In children, the pain and distress of recurrent procedures are an important additional burden that persists throughout their disease. Spinetta and Maloney124 found that, unlike children with noncancerous chronic diseases, children with leukemia reported greater anxiety with more frequent visits. There is no accommodation or habituation to the illness or to the attendant procedures. In addition to these physica causes of pain, the pain of cancer, according to Noyesg3 quoting Montaigne, is “doubly painful because it threatens us with death.” The hopelessness and depression that this notion engenders potentiate the cycle of pain. As mentioned, however, young children may have some refuge from this hopelessness. Cancer is usually not painful in its early stages but becomes increasingly painful as it progresses. Borncal reports that one 52

third of adult patients experience moderate to severe pain in intermediate states of the disease, while two thirds or more experience severe pain during its terminal stages. He reports that, despite adequate availa le technology to ablate it, up to 85% of patients with cancer di The treatment for pain in cancer has been reviewed by man authors. Adequate analgesia is its cornerstone, however, Twycross135 and other workers in the hospice movement e of analgesia in seriously ill pamade great strides in the tients. Relief of anxiety a depression and provision of emotional support are critical. SICKLE

CELL

DIE~EASE

Sickle cell anemia is the most common bemoglobinopathy found in the United States, with an incidence in American blacks of between 0.3% and l.3%.73 It is a significant cause of sympmortality and morbidity in c ildren. Pain is a prominent tom of the disease during th o-occlusive crises, which occur to result from obstruction of intermittently. Pain is assum lood flow in the capillarie to an increase in number of sickle cells. The obstruction of flow results in hypoxia, tissue damage, and pain, although the exact origin of the pain remains obscure. Crises can last from several days to several weeks. Generally, patients are assumed to have severe disease if they have painful vaso-occlusive crises one to two times per month with concurrent hospitalizations. Moderate disease is defined as crises two to six times yearly, and mild disease one or no painful episodes per year.i12 Recently, Greenberg et a1.43 conducted the first prospective study of the epidemiology of vaso-occlusive crises and found that 30% of the 94 patients had no crises witbin 21 months, 71% had two or fewer crises, and 25% had more than five crises, with a maximum of eight during this sample period. Rozzell et a1.112 have determined that a variety of factors can precipitate a pain crisis in sickle cell disease-residual sickle cell complications (sickle cell lung, right upper quadrant syndrome, leg ulcers, renal disease), presence of another disease, infections, overexertion and subsequent dehydration, weather changes, alcohol ingestion, cigarette smoking, and emotional distress. The pain in children with sick e cell disease should not be attributed uniformly to vase-o~cI~sive origins, however. Infection, cholelithiasis, lower lung disease, and bone infarcts should also be considered.ir5 Treatment involves adequate analgesics and irin therapy does not appear to prebydration. Prophylactic vent subsequent crises orphine is the drug of choice for control of pain in children with sickle cell disease. It is preferable to meperidine, which has been plicated in the production of seizures in such children. Sup mental oxygen is necessary 53

only for documented hypoxia; prolonged oxygen use may cause a fall in erythropoietin, which will agg -:aate the existing anemia. Although addiction is a widespread Jar in the prolonged treatment of children and adults in pair from sickle cell disease, there have been no specific studies on ne problem of addiction in individuals with sickle cell disease. It most likely approximates the addiction rate in cancer patients, which has been well studied and is not a significant problem, even for patients who have been on high doses of narcotics for long periods of time. This fear should not prevent the adequate treatment of pain in patients with sickle cell disease. Additional treatments, such as hypnotherapy and biofeedback, are under investigation for patients with sickle cell disease. Fluidotherapy, a new heat treatment modality, is also being studied.‘i5 Emotional support is critical for these individuals, who suffer from a noncurable, life-shortening, frequently painful illness. Group meetings of sickle cell patients, individual psychotherapy and counseling, and the use of psychopharmacologic agents for anxiety and depression should be considered. To improve compliance, physicians should be certain that patients and their families have a thorough understanding of the disease. In a study of 68 mothers of children who had sickle cell disease for an average of 7 years, Whitten et al. report that 22% of the mothers did not understand the pattern of inheritance of the disease, 35% did not understand the etiology of their child’s pain, 55% could not describe what anemia was, and more than 50% were unaware of their child’s feelings about the disease.r4i Education and increased understanding may lead to increased compliance with prescribed medical regimens and ease the burden of illness on the child. RECURRENTPAINS In addition to the less common causes of pain in children, there is a group of common recurrent pains, including recurrent abdominal pain, headache, and limb pain. Because these problems are chronic and rarely require specific pain management, they are not within the specific purview of this volume and will be addressed as a group. The reader is referred to excellent reviews for more detailed information.4’ ‘a 41, ro2, 12’ Recurrent abdominal, limb, and head pain is extremely common in children, occurring in 10%-15%,4zg7 15%,io1 and 15%20%, g7, iso respectively, with girls having a slight preponderance of symptoms as middle childhood progresses. Reviews of these recurrent pains in children usually present a long list of possible etiologies, but rarely are organic explanations found. Approximately 7% of children with recurrent abdominal pain are found 54

to have organic etiologies, usually urinary tract pathology.” Some 3%-4% of limb pain is deemed organiqgs and an organic cause is found in 5% of children with headache. When organic disease is not present, psychiatric explanations are classically invoked. Stress, emotional lability, family pathology, and personality style are often implicated in diagnoses such as psychogenic abdominal pain, tension headache, psychogenic rheumatism, etc. The availa e data allowing us to assume a strictly psychogenic etiology r the majority of these problems are far from conclusive. For example, although Apley’s classic investigation* of children with recurrent abdominal pain revealed a high inciden sonality abnormalities (“highly strung, fussy, and ex appetite changes, and sleep disturbances in these ch is examiners were pediatricians and psychologists who were t blinded to the child’s pain status. In addition, the effect of recurrent pain on personality and family process was not evaluated, and therefore one cannot assume that emotional fa s bad a direct causal role in the production of these pains. er studies have similar methodological flaws. Barr,’ writing about recurrent abdominal pain, developed an alternative model to the organic/psychogenic dichotomy. He suggested that children without definable organic disease, clear psychopathology, or psychogenic indicators (school refusal, recent loss of a significant other secondary gain, conversion reaction, modeling of an ill indivi ual), should be assumed to have nctional pain. By this be suggests that normal physiologic ses such as developmental lactose intolerance, chronic etention, intestinal gas symptoms, or increased awareness of physiologic sensations can produce pain in certain individuals. This assumption does not preclude the possibility that the stresses of childhood or family life have no role in precipitating the discomfort, but assumes instead a less reductionistic model of pain production, allowing for a variety of interacting factors, both psychological and bi ogic, to produce pain. This model has relevance to headache an limb pain as well. Treatment for these recurrent problems is aimed at addressing underlying etiologies when possible and providing reassurance to the family that organic pathology has been ruled out but will continue to be mon.itored in th ture. The reality of the child’s complaint should be accepted. d analgesics, behavioral therapies (Table 5) and counseling about coping with intermittent discomfort will help the hild and family adjust to these common and often distressing

The management enormous challenge

of a child with severe burns presents an to medical and nursing staff. In addition to 55

TABLE 5.--BEHAVIORALPAINMANAGEMENTSUGGESTIONSFORPARENTS (SPECIFICALLYFORCHILDRENWITHHEADACHES, BUT APPLICABLETO RECUREENT PAINS)* ENCOURAGENORMALACTIVITY 1. Frequent approval for maintaining normal activity 2. Encourage child to stay calm and practice relaxation ble. 3. Advocate daily school attendance or stay in school

patterns. procedures as the

ALL

where

feasi-

norm.

DISCOURAGE PAINBEHAVIOR 1. Ignore excessive complaining, pain gestures, and requests for special treatment and assistance. Instruct others to do the same if necessary. 2. Dispense medications for symptomatic relief according to directions and follow recommended time sequence. 3. Evaluate whether the consequence of the headache is to avoid or escape from an activity or situation. If so, consider maintaining things as they are or alternative (e.g., bed rest) that has little appeal to child. 4. Avoid questioning about presence of headache or status of headache. *From Masek pain in children. sion.

B.J., Russo D.C., Varni J.W.: Behavioral Pediatr. Clin. North A. 31:1122, 1984.

approaches Reproduced

to chronic by permis-

infection, nutrition, fluid and electrolyte imbalance, and psychological problems, the burned child experiences significant pain. This pain is produced not only by the burn but also by its therapy (debridement, dressing changes, and physical therapy). Perry and Heidrich104 surveyed burn centers to ascertain how pain during debridement was managed. They found that 17% of the centers did not suggest the use of analgesia or anesthesia for debridement in young children, while all centers use analgesics in adults undergoing similar procedures. Centers were also less likely to use psychotropic drugs in conjunction with narcotics in children (24% of children vs. 52% of adults). Finally, despite the high percentage of centers that recommend using no narcotics, psychotropics, or analgesia at all in children, personnel reported that children and adults seem to experience the same degree of pain witch burns. In a study we performed at a large teaching hospital,‘i4 children hospitalized for treatment of more moderate burns (< 20% of body surface area) received an average of 1.3 doses of narcotics per day, while adults with similar burns received 3.60 doses per day. A number of methods have been employed to control burn pain in children and adults, including narcotics (methadone and morphine), anesthetics (nitrous oxide, ketamine, methoxyflurane), and behavioral methods (behavior modification, hypnosis, psychotherapy, relaxation). There is no consensus in the literature about the most efficacious therapy. When narcotics are used, however, they should be given IV. Subdermal or IM injections will not be uniformly absorbed in the immediate postburn period because of systemic hypovolemia and therefore will offer little analgesia to the patient. When systemic circulation nor56

malizes, the patient is at risk for respiratory depression and obtundation because Poole analgesics suddenly enter the bloo stream.62 Kavanagh67, 68 has to dressing changes i their depression and model for psychological mention, which may lessen perceived pain. Instead of tra onal, standard nursing care, which is supportive and uses d action, verbal soothing, and pain medication during dressing changes, Kavanagh substituted an approach that emphasizes patient control and predictability of aversive events. In practice, this involved directing the patient to remove his own dressing, to assist with debridement in limited ways, and have some role in deciding when the process was to occur. By use of age-~~~ro~ria~e control, the child became involved in the task instead of distracted from it. To improve predictability, the nurse de rided patients only when she was wearing a red apron and only at predictable times. When the nurse was not in red, the patient was assured that these painful procedures would not take place and therefore could relate to tbe nurse and other hospital personnel in a less anxious and fearful way. Through the use of such t~c~ni~~es, Kavanagh narcotic premeditation, nstrated fewer acting out episodes, syehopathology that has traditionand prevented some of ally occurred in burned children. In summary, the literature on burned children suggests that the more vigorous use of IV analgesics and anesthetics, coupled with creating a more predictable, controllable environment, may more maximally comfort the child in the desperate time following a severe burn.

Adequate pain control in the postoperative period is important for both humanitarian and clinical reasons, The pain-free patient will be more mobile and able to cough and breathe more easily, thus reducing the potential for postoperative eomplications. Despite the importan perative pain control, most as well as children suggest studies reviewing this area that undermedication of operative patient is the norm. 27, 78, “9 lz5, 133 This tendency to und tive patients has been termed ““tight-fist editorial in The Lanced. An editorial in the British Medical Journal108 has suggested that postoperative undermedication of pain is “an indictment of rnod~r~ medicine.” The problem of undermedi~~tio~ for postoperative pain is even more pronounced in children. In the few available studies in which postoperative care has been compared in children and adults, investigators have reported marked discrepancies in an57

algesic-prescribing practices. For example, Beyer et all4 compared children and adults following cardiac surgery and found that for the first 5 days following surgery, in a matched sample of adults and children, children received 30% of the prescribed analgesics, while adults received 70%. Well4 found marked discrepancies between children and adults in the postoperative use of analgesics after herniorraphies and appendectomies. Mather and Mackie” found that analgesics were not ordered for 16% of the children they investigated postsurgically, and narcotics were not administered postoperatively to 39% of the children. In addition, they found that nurses tended to select nonnarcotic medication, or the lowest doses of narcotic medication, if physicians’ orders gave them a choice or a range of dosage. Despite this limited narcotic use, 75% of the children interviewed in their study reported pain on the operative day, and 47% reported pain on subsequent days. Most current reviews of adult postoperative pain control suggest that IM meperidine or morphine is most effective and should be used for the first 24-48 hours postoperatively.31z 136 When the severe pain has subsided, oral therapy is indicated. Investigators agree that it is better to anticipate pain and treat it prophylactically than to treat it once it has returned. Careful attention should be paid to each patient’s narcotic need, since there is wide variability in individual morphine pharmacokinetits. Finally, these reviews all suggest that patients frequently do not request medication for pain, and therefore preoperative instruction about the availability of postoperative pain control is helpful for most patients. There are no reviews of postoperative pain control for children in the literature at present. A number of developments in the adult literature, however, have implications for children. The use of IV analgesics, given either episodically or through continuous infusion, should strongly be considered for children experiencing postoperative pain. R-utter et a1.113 have reported that continuous infusion of morphine provides better pain relief with a lower required dosage. IV administration has an additional advantage in children of not requiring repeated IM injections. Another recent development in pain control has been the use of self-administered, patient-controlled analgesia systems.‘l, iz2 In such systems, the patient can activate a device linked to a timer that initiates an infusion of narcotics. This device gives patients more control over their pain, and patients report a more comfortable postoperative course when using them. Such devices have been in use for 10 years and have been found to be safe and effective. For children, parents could be called on to activate the device when they notice that their child is experiencing discomfort. This may allow parents to have an active and gratifying role in nursing their child, Although there has been no re58

search about patient~adm~n~s~ere~ analgesia in children, it is clearly something that should be considered. Finally, the use of TE S has been suggested for postoperative incisional pain in children as a nonpharmacologic means of pain control. This has not been studied but offers a number of theoretical advantages such as increased mobility and freedom from injection.

Narcotics may be necessary to reduce pain during a number of diagnostic and therapeutic procedures performed on children. Sedation is also sometimes necessary to prevent restlessness in children who are too young to be fully cooperative. To address this simultaneous need, the “‘cardiac” or “lytic” cocktail was first developed for use on children during cardiac catheterizations in 1958 by Smith and colleagues.123 This mixture of meperidine (Demerol), promethazine (Phenergan), and chlorpromazine (Thorazine) provides both sedation and pain control. Its use has been extended to include other procedures which cause discomfort (bone marrow aspirations, dental sedation, subdural taps, myelography, pneumoencephalography)21 and for pain-free procedures in which sedation is required (CT scans, EEG, ophthalmologic examination). All three drugs in the cocktail have a sedative effect, while the ~b~~otbiazines offer an additional TABLE

B.-DEEP

BODY

WEIGHT

SEDATION MIXTURE FOR PROCEDURES w CHILDREN*

(lb)

10

i5 20 25 30

40 50 60 70 80 90 and over

DOSAGE SCHEDULE:” DOSE OF SEDATIVE MIXTURE

(cc) 0.4 0.5 0.75 0.85

1.0 1.5 1.6 1.7 1.8 1.9 2.0

*From Bray P.F.: Neurology in Pediatrics. Chicago, Year Book Medical PLtblishers, Inc., 1969, p. 487. Reproduced by permission. 1 cc of the sedative mixture contains: meperidine (Demerol) 25 chlorpromazine (Thorazine) 6.25 it; promethazine (Phenergan) 6.25 mg 59

antiemetic effect, and meperidine offers analgesia. Numerous investigators have reported on the efficacy and safety of this mixture.2S 21, 123 The mixture typically contains 25 mg of meperidine, 6.25 of promethazine, and 6.25 mg of chlorpromazine in a l-ml solution. Depending on the weight of the child (Table 6), the initial dose is given IM 45 minutes before the procedure is scheduled to begin. For CT scan premeditation, Anderson and Osborne2 found an improved success rate by increasing the dosage 10%. Although this method continues to be useful for procedures that are painful, it is less than ideal for simple sedation for painfree procedures. The cocktail involves an IM injection which is often painful, the cocktail is confusing to compound, which may result in overdosage or underdosage, and the two phenothiazines in the mixture lower the seizure threshold, which may be problematic in seizure-prone patients. Further research is necessary to develop safe, efficacious oral sedation in children undergoing painless techniques that require a still child, such as the newer imaging techniques (magnetic resonance imaging, CT scan).

MINOR TRAUMA The approach to pediatric pain control associated with minor surgery in an emergency room or office setting has changed little over the past two decades. Pain control is obtained either through local anesthesia, IM sedation using a pediatric “cocktail” of narcotics and phenothiazines, distraction, or some combination of approaches. The dental literature has focused more clearly on this problem and may give the physician some new directions. One dental technique, the use of nitrous oxide, has been reported in pediatric settings, with good results. Griffin et a1.44 report the use of inhaled nitrous oxide sedation, administered by the pediatrician in his office, in 3,000 simple procedures in children, such as laceration repairs or simple fractures. They report no significant side effects, except for vomiting in nine patients, and found that the procedure decreased the fear and apprehension in children and their parents. Their study was uncontrolled and its replication is vital before such procedure becomes widespread. SUMMARY Focused research on pain and pain control in children has developed primarily in the last 10 years and even now is woefully inadequate in relation to the magnitude of the problem. The available research, inferences from the adult literature, and anecdotal information all indicate the elusive nature of pain. Pain is not solely a fixed neurophysiologic response to a noxious stimulus but a product of the interaction of many variables such as

60

age, cognitive set, personality, ethnic background, and emotional state. These factors exert a tremendous influence on the suffering which surroun pain message. Technology exists at present to eliminate stantially reduce pain in almost all cases. There remains; ever, a tendency, which is even more pronounced with respect to children, to ‘underestimate or ignore pain. In an overall approach to pain in children, the following points should be considered: 1. A high index of suspicion is necessary to determine if children are experiencing pain since they may have difficulty verbalizing their discomfort. In infants, physiologic variables should be considered (incre ate, palmar sweating, increased respiratory rate), choolers, time should be lly understands the word taken to ascertain that the “‘pain” if it is used in ques . Some method of continuous monitoring, such as a visual analogue scan, should be considered as part of the treatment plan. 2. Adequate analgesia ould be provided. The appropriate dose should be administer at the appropriate pharmacokinetic time. Too little medicati may cause obsessive attention to medication-related issues. Too much medication may cause sedation and lack of mental clarity, which is often anxiety-producing for both the parents and the child. The usefulness of p.r.n. medication has been seriously questioned and a time-contingent as opposed to pain-contingent strategy should be applied. Fears of addiction are generally unwarranted. Adjunctive medication may increase the value of offere narcotics and counteract some of their side effects. 3. Although this rno~o~a~~ s focused more attention on cologic approaches to pain, pharmacologic than on no~~b~ this is merely a reflection of available data and not necessarily of relative importance. The importance of distraction from pain by nursing, medical, or child life personnel using play techniques cannot be overestimated. Every attempt should be made to relax the child by using creative strategies. Preparation of the child for procedures is often helpful as some of the fear of the unknown is eliminated. Protecting the child from fear of abandonment by assuring parents an important role in their ehilcl’s treatment regimen is also important. In summary, the ultimate goal should be safe, effective pain relief for all children. The mere recognition of the existence of pain in children is an important first step toward improving their car esearch base wkich is necessary to improve this area. AngelI’s editorial provides an . “Pain is soul destroying. No patient should have to endure’ intense pain unnecessarily. The quality of mercy is essential to the practice of medicine. Here, of all places, it should not be strained.” 61

ACKNOWLEDGMENTS The author thanks Drs. Joseph 6. Cullina, Paul H. Dworkin, Milton Markowitz, and Ann Milanese, and Ms. Carlota P. Schechter for their continuous support of this project; Dr. Jerome Jaffe, Dr. Fred Lovejoy, and Mr. Peter Lacouture for their critical review of the manuscript; Dr. Arnold Altman, for critical review of the hematology and oncology sections; Mr. William Woodward for critical review of the manuscript and adaptation of the pharmacologic tables; Ms. Teal Friedmann for library assistance; and Ms. Lorraine Scrivano for endless patience and secretarial support. REFERENCES 1. Altman A., Schwartz A.: Malignant Diseases of Infancy, Childhood, and Adolescence. Philadelphia, W.B. Saunders Co., 1983. 2. Anderson R.E., Osborne A.G.: Efficacy of single sedation for pediatric computed tomography. Radiology, 124739-740, 1977. 3. Angel1 M.: The quality of mercy. N. Engl. J. Med. 306:98-99, 1982. 4. Apley J.: The Child zvith Abdominal Pains. Oxford, England, Blackwell Scientific Publications, 1975. J. Psychosom. Res. 20:383-389, 1976. 5. Apley J.: Pain in childhood. abdominal oain. in Gabel S. (ed.1: Behavioral Problems 6. Barr R.: Recurrent in Childhood: A Primary Care Approach. New York, Grune & Stratton, Inc., 1981. 7. Beales J.G., Kean J.H., Lennox-Holt P.J.: The child’s perception of the disease and the experience of pain in juvenile chronic arthritis. J. Rheum. 10:61-65, 1983. 8. Beaumont A., Hughes J.: Biology of opioid peptides. Annu. Rev. Pharmacol. Toxicol. 19:246-267, 1979. 9. Beecher H.K.: Relationship of significance of wound to the pain experience. JAMA 161:1609-1613,1956. 10. Beecher H.K.: Measurement of Subjective Responses: Quantitative Effects of Drugs. New York, Oxford University Press, 1959. 11, Bennett R.L., Batenhorst R.L., Bivins B.A., et al.: Patient controlled analgesia: A new concept of postoperative pain relief. Ann. Surg. 195:700-705, 1982. 12 Benson H., Beary J.F., Carol M.P.: The relaxation response. Psychiatry 37:37-46, 1974. 12 Benson H.: The Relaxation Response. New York, William Morrow, 1975. 14. Beyer J.E., DeGood D.E., Ashley L.C., et al.: Patterns of postoperative analgesic use with adults and children following cardiac surgery. Pain 17:7181, 1983. 15. Blumer D., Heilbronn M.: The pain-prone disorder: A clinical and psychological profile. Psychosomatics 22:395-402, 1981. 16. Blumetti A.E., Modesti L.M.: Psychological predictors of success or failure of surgical intervention for intractable back pain, in Bonica J.J., Albe-Fessard D. (eds.): Advances in Pain Research and Therapy. New York, Raven Press, 1976, vol. 2. 17. Bond M.F.: Pain-Zts Nature, Analysis, and Treatment. New York, Churchill Livingstone, 1979, p. 24. 18. Bonica J.J.: Neurophysiologic and pathologic aspects of acute and chronic pain. Arch. Surg. 112:750-761, 1977. 19. Bonica J.J.: Pain research and therapy: Past and current status and future needs, in Ng L.K., Bonica J.J. (eds.): Pain, Discomfort, and Humanitarian Care. New York, Elsevier-North Holland, 1980. 62 A”.

20.

21. 22. 23. 24. 25. 26.

27. 28. 29.

30. 31. 32.

33. 34. 35. 36. 37. 38. 39.

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SERF-ASSESSMENT 1. 2. 3. 4. 5. 6. 7.

False False True False True False False

8. 9. 10. 11. 12. 13.

False d b c a b

67