(Garrison, 1923; Still, 1931). Crying, restlessness, and sleeplessness were regarded as the primary symptoms of a child \200\231s pain and dis- tress (Unruh, 1992). One of the most reported pains of childhood prior to the eight- eenth and nineteenth centur ies was teething pain. Th e treatments for teething pain (Table 1.1 ) are fascinating to th e modern reader and illustrate the underlying concern with which a child-specifi c pain was regarded throughout those centuries, and the ways in which remedies were passed down and m odifi ed over time. It was not uncommon for children to die in infancy and childhood when t hey were teething though illness and death were likely due to issues other than teething (M cGrath and Unruh, 1987). Determining whether a child was in pain was a challenge and not surprisingly generally dete rmined by appeals to observation of changes in the child \200\231s behavior. Aurelianus (fi ft h century ce ) illustrates the emphasis on a child \200\231s behavior as an indicator o f pain: Th e child groans in its sleep, rolls about, gnashes its teeth, tends to lie prone, cries o ut suddenly, or falls silent, is seized with convulsions, sometimes becomes somnolent, the face becomes emaciated and loses its color; the child gets cold and answers questions with diffi culty; sometimes throws itself about with outstretched hands, working itself into per spiration. (Quoted in Garrison, 1923, p. 47) A brief early history from ancient times to the mid nineteenth century Th e earliest medica l writings about the pain and diseases of chil- dren do not provide much information about symptoms of pain and disease in children but they do illustrate an understanding that child ren could not be treated medically as if they were adults. For example, the Atharva Veda of India (1500 \200\223800 bce ) provided pediatric incantations for headache, earache, and m usculoskeletal pains (Garrison, 1923). Th e Susruta Samhita of India (second cen- tury bce ) gave dosages of drugs and herbal remedies for children separately from adults and advised administering them with milk, clarifi ed butter, or in a plaster spread on the breasts of the nurse (Garrison, 1923). Hippocrates (about 460 \200\223357 bce ), Celsus (25 bce \200 \22350 ce ), Soranus (second century CE), Galen (130 \200\223200 ce ), Oribasius (325 \200 \223403 ce ), Aurelianus (fi ft h century ce ), Aetius (sixth century ce ), and Aegineta (s eventh century ce ) all contributed to treatment of disease in infancy and childhood in the ir time period and beyond, in Greece and Rome, and in the Arab world. Th e Hippocratic writ ings of the fi ft h and fourth centuries bce described constitutional diff erences between adults and children, and gave diff erent doses of herbal remedies and means of administrati on Th ough changes in general behavior were important, crying was usually regarded as the chie f indicator of a child \200\231s pain. Some physi- cians, such as Omnibonus Ferrarius (1577 ) (an Italian physician), (Still 1931), and Starr (1895) and Holt (1897) (both American phy sicians), believed that children only cried if there was a rea- son associated with distres s. Both Starr (1895) and Holt (1897, 1908) associated diff erent features of cries with spe cifi c illnesses and severity of pain. For example, a sudden, very loud and parox- ysmal sh riek was described as hydrencephalic cry associated with headache (Starr, 1895, p. 6). Holt (1987) described acute pain as having a sharp and piercing cry that was usually accompanie d by contracting facial features and drawing up the legs and sometimes falling into an exha usted sleep. He ascribed these pains to earache and colic. Starr (1895) may have been the f i rst physician to describe facial expression of pain. He also used these features to ident ify the source of pain: Th e picture (of a healthy child) is altered by the onset of any illness, the change being in proportion to the severity of the attack. An expression of anxiety or suff ering appears , or the features become pinched and the lines are seen about the eyes and mouth. Pain most of all sets its SECTION 1 introduction 4 Table 1.1 Historical treatments of children \200\231s teething pain Source Treatments Soranus, 2nd century ce \200\230Before teething, the gums should be gently rubbed with oil or fats, and the child may be permitted to suck fat bacon without swallowing, but this should cease when the teeth appear. Th e gums should not be irritated by butter or acid substances, and if there is mu ch in \202 ammation, poulticing, and sponging are recommended \200\231 (quoted in Garrison , 1923, p. 46) Oribasious, 325 \200\223403 ce \200\230If they are in pain, smear [the gums] with dog \200\231s milk or with hare \200 \231s brain; this works also if eaten. But if a tooth is coming through with di \203 culty , smear cyperus with butter and oil-of-lilies over the part where it is erupting \200\231 ( quoted in Still, 1931, p. 38) Aetious, 6th century ce \200\230He advises the root of colocynth, hung on the child in a gold or silver case, or b rambleroot, or the tooth of a viper, especially of a male viper, set in gold, or a green ja sper suspended on the neck so as to hang down over the stomach \200\231 (quoted in Still, 1 931, p. 40) Rhazes, 859 \200\223932 ce \200\230And the treatment of it, when the gum is swollen, is that the gum should be rubbed a little with the \201 nger, and afterwards with oil and hen \200\231s fat or hare \200 \231s brain or dog \200\231s milk; and apply to the child \200\231s head water in which the re have been boiled camomile and dill, and put plasters which have a dispersing e \200 ect on his jaws; and if the pain in the part increases after this, take butter and oil of laur els, mix together and apply over the part; or take cow \200\231s butter and marrow from the thigh, and apply; and if the points of the teeth have appeared, put over the whole head an d neck clean wool, and let some tepid water be sprinkled on the wool each day \200\231 (quo ted in Still 1931, pp. 46 \200\22347) Avicenna, 980 \200\2231036 ce \200\230For burning pain in the gums apply oil and wax as an epitheme or use salted \202 esh which is a little \200\234high \200\235 \200\231 (quoted in Gruner, 1930, p. 372) Phaer, 1546 ce \200\230Th ere be divers things that are good to procure as easy breeding of teeth, among them the chiefest is to anoint the gummes with the braynes of an hare nyxte with as much ca pons grece and hony, or any of these thynges alone is exceadynge good to supple the gummes and the synewes \200 And whan the peyne is greatte and intolerable with apostema or in \202 ammacion of the gummes, it is good to make an ointment of oile of roses with the juyce of morelle otherwise called nightshade, and in lack of it annoint the jawes within with a little fresshe butter and honye \200\231 (quoted in Still, 1931, p. 121) Sainte-Marthe, 1569 ce \200\230Hare \200\231s brain, honey and red coral ring as amulet \200\231 (cited in Ruhrah , 1925) Ferrarius, 1577 ce \200\230A dead man \200\231s tooth in the opinion of some, through some particular virtue when hung on the neck of an infant, soothes and disperses the pain of teething \200\231 (qu oted in Still, 1931, p. 156) Primerose, 1659 ce \200\230Tooth of a dog, wolf or male viper hung around the neck to ease teething pain \200 \231 (cited in Still, 1931) Early modern history starts with anesthesia 1840 \200\2231950 Th e experience of pain was t ransformed by the development of anesthesia in the nineteenth century. In 1842, Crawford Lo ng used diethyl ether to excise a cyst from a patient \200\231s neck (Long, 1849), and then in 1846 William Morton gave a public demonstration of the use of ether for a dental proced ure (Costarino and Downes, 2005). Children were involved in the earliest clinical applicati ons of anesthesia; the third patient who received ether from Long was an 8-year-old boy who se diseased toe was amputated on 8 July 1842 (Stewart, 1989). John Snow (1885), Queen Victo ria \200\231s anesthetist, started using diethyl ether for children in 1847 and 10 years la ter reported on his use of chloroform with several hundred children, 186 of whom were infan ts (Costarino and Downes, 2005). While children commonly received anesthesia for surgery fr om the beginning, they were also perceived to have more problems associ- ated with anesthes ia such as nausea and vomiting, hypotension, respiratory depression, and cardiac arrest, es pecially with chloro- form (Costarino and Downes, 2005). Th e fi rst recorded deaths due to anesthesia occurred in children (Stewart, 1989). Some invasive procedures were considered so short or so minor that anaesthe- sia was thought not to be required. For example, Wharto n (1895) did not consider a tracheotomy painful if there was marked dysp- noea, and thought that it was only the fi rst incision that was pain- ful. Similarly, Casselberry (1895) did not feel an anesthetic was needed for a tonsillectomy because of the brevity of the proced ure unless the adenoids were also to be removed. Pernick (1985) noted mark upon the countenance, and by noting the features aff ected it is oft en possible to fi x the seat of serious disease. Th us, contraction of the brow denotes pain in the head; sh arpness of the nostrils, pain in the chest; and a drawing up of the upper lip, pain in the abdomen. (Starr 1895, pp. 3 \200\2234) At least two surgical procedures, trepanation (a hole bored in the skull to treat headaches , mental illness, and convulsions) and circumcision, were performed on children in the anci ent world throughout history (Liskowski, 1967). Other pediatric surger- ies included repair of inguinal hernia, and harelip, tonsillec- tomy, and severance of the frenulum of the ton gue (Mettler and Mettler, 1947). Opium, hyoscyamus, mandragora, and wine were used for pain relief during surgery (e.g. Celsus 25 bce \200\22350 ce and Avicenna 980 \200\2231036 ce ) (McGrath and Unruh, 1987; Mettler and Mettler, 1947) but physical restraint was the more common approach. For children, surgical procedures were exceedingly painful and diffi cult for the patient and physician. Celsus \200\231 advice for the surgeon was: A chirurgien must have a strong, stable and intrepid hand and a mind resolute and merciless ; so that to heal him that he taketh in hand, he be not moved to make more haste than the t hing requireth, or to cut less than is needful, but which doth all things as if he were not hing aff ected with their cries. (Quoted in Griffi th, 1951, p. 127) Children suff ered when they had pain throughout this period (Newton, 2011). Although there is evidence that children were also cared about, and eff orts made to manage their pain (M cGrath and Unruh, 1987), it was anesthesia that off ered the fi rst prospect of signifi can t pain relief. CHAPTER 1 history of pain in children 5 that procedures other than amputations of limbs were oft en con- sidered minor. as blood draws, lancing of infections, and exposure to pin pricks during sleep. She observe d crying and defensive escape behavior but reported them as complex and advanced, refl exiv e and instinc- tive behaviors. In 1941, McGraw used pin pricks to examine the maturation of nerves in 75 children from infancy to 4 years. She maintained that the diff use body movem ents of neonates with cry- ing refl ected a limited sensitivity to pain in the fi rst 2 wee ks of life and that it was unlikely for there to be any neural mediation above the thalamus . In 1898, August Bier used cocaine to induce spinal anesthesia in six patients, two of whom were children but he did not per- ceive spinal anesthesia to be benefi cial (Brown, 2012). By 1910, three papers had been published in Th e Lancet each referring to 100 or more pedia tric cases in which spinal anesthetics, rather than general anesthesia, were used (Gray, 19 09a, 1909b, 1910). Regional anesthesia may have evolved due to the associated risks of gene ral anesthesia in children but as pediatric general anesthesia improved in the 1930s to 195 0s, regional anaesthet- ics were less frequently used and are still not widespread (Brown, 2012). But there continued to be opposing points of view. Charles Robson, anesthetist at the Hospi tal for Sick Children in Toronto, perhaps the fi rst pediatric anaesthesiologist (Mai and Y aster, 2011), vehemently rejected outright assumptions about infant insensitivity to pain: Th e advancement of pediatric pain management during surgery was dependent on the developme nt of anesthetic agents, manage- ment of negative side eff ects of these agents, adequate t raining of physicians in the use of anesthetics, and development of anaes- thetic equipment that was appropriate for use with infants and chil- dren. Rendell-Baker (1992) described t he historical evolution of pediatric anesthesia equipment as having diff erent developmen- tal phases including: use of open drop mask for chloroform; intro- duction of tracheal intu bation (beginning in 1909); development of various breathing systems (Magill \200\231s brea thing system, Mapleson E T-piece breathing system, pediatric laryngoscopes, pediatric trach eal tubes, the Crowe \200\223Davis mouth gag, the laryngeal mask airway); design of cyclopr opane and carbon dioxide absorption sys- tems (non-rebreathing valves); the T-piece system; specialization of pediatric anesthesia as a medical subspecialty; use of halothane and low -dead space pediatric face masks and related equipment; introduction of standard breathing systems; and use of constant positive airway pressure and intermittent mandatory ventilatio n. Th e fi rst pediatric anesthetic textbook, Anesthesia in Children by Langton Hewer, appe ared in 1923, with a second textbook, Leigh and Belton \200\231s Pediatric Anesthesia , ava ilable in 1948. First, it has been stated that infants under seven days of age do not require anesthetics f or operations \200\224that their association tracts for pain are not fully established and that minor operations may be car- ried out without any damaging eff ects on the infant. Per sonally I do not believe this and it is simply vivisection to operate on a conscious scream ing wriggling infant without using a general or local anesthetic. (Robson, 1925, p. 235) Robson used open-drop ether and cyclopropane along with tra- cheal intubation for infant an esthesia (Mai and Yaster, 2011). Views such as Robson \200\231s were probably in the minority. Th ere is lit- tle discussion about pain in early textbooks about pediatric anaes- thesia, not even with respect to neon ates. Smith \200\231s Th e Physiology of the Newborn Infant (1945) did not mention pain at all. Leight and Belton (1948) made only one substantive comment about pain: Newborn infants are not as sensitive to pain and some degree of anal- gesia is present with out anesthetic. Most infants, however, do have some pain sensation even at birth and one ca nnot rely on the old adage that there is no pain sensation for the fi rst three weeks of li fe. It is nearer the truth to say that sensitivity to pain is decreased. Since there is som e basic analgesia, very low concentrations of anesthetic agent will produce complete analge sia. (p. 30) Th e primary advantage of anesthesia was the relief of pain with the secondary eff ect of p ermitting increasingly more complex (and invasive) surgical procedures. At the outset, in i ts earliest period, the benefi ciaries were most likely to be women, white people, young ch ildren, and people from upper and middle classes (Jackson Rees, 1991). Children were viewed as more sensitive to pain, and more diffi cult to control if they were anxious and fearful about the pro- cedure (Pernick, 1985). But with respect to the pain experience of infants, there was disagreement about the best approach. On the one hand, there were those physicia ns, like Eliza Th omas (1849), who regarded infants as hypersensitive to pain (cited in Per nick, 1985). Th ere were other physicians whose views resonated with Henry Bigelow (1848) w ho wrote: \200\230Th e fact that it [infant] has nei- ther the anticipation nor the rememb rance of suff ering, however severe, seems to render this stage of narcoticism [full anesth esia] unnecessary \200\231 (quoted in Pernick 1985, p. 172). Stewart (1989) wrote that infa nts were considered ideal patients for surgery by some because they were considered relativ ely insensitive to pain, unable to appreciate it, and even capable of sleeping through the surgery. In 1938, Th orek wrote: \200\230Oft en no anesthesia is required. A sucker consis ting of a sponge dipped in some sugar will oft en suffi ce to calm a baby \200\231 (p. 2021 ). By the mid twentieth century, the prevailing view, that infants had reduced sensitivity to pain, provided an accepted position for the use of minimal anesthesia for surgery on infant s. In the 1950s, Gordon Jackson Rees in Liverpool, England, introduced an approach that cam e to be known as the Liverpool technique. He modifi ed a part of the pediatric anesthetic e quipment to permit better monitoring of respiratory movements of anesthetized chil- dren an d provide intermittent ventilation if needed (Costarino and Downes, 2005). He also introduc ed curare and other relaxants into practice and nitrous oxide and oxygen anesthesia without ether (Jackson Rees, 1960). In his 1950 discussion about anesthesia in the newborn, Jackso n Rees argued that the newborn was substan- tially diff erent from an adult in neuromuscula r structure and physi- ology (mechanical diff erences, sensitivity of the respiratory syste m, muscle tone). While he supported using muscle relaxants to reduce the amount of anesthet ic agents, he believed that control of respi- ration was possible with light anesthesia wit hout muscle relaxants for infants because of these structural and physiological diff er- en ces. He believed the \200\230operative risk \200\231 to full-term infants was slight becau se fetal cord blood levels of corticosteroids at birth paralleled those of the mother, henc e surgical trauma was less at birth but then increased rapidly during the fi rst week of li fe. Th e optimum operative period was regarded by Jackson Rees (1950) to be the fi rst 24 h ours of life. Jackson Rees (1950) noted that Leigh and Belton Th is view of relative insensitivity to pain in infants seemed to be supported by studies t hat endeavored to elicit pain. In 1917, Blanton reported on studies of the response of infa nts to procedures such SECTION 1 introduction 6 (1948) had suggested premedication with morphine for very young infants with morphine but b elieved it was generally not necessary: developments occurred that brought scientifi c thinking to the area and widespread realizat ion in the health system that pediatric pain was an important issue. Development of the fi eld of pediatric pain was, and continues to be, uneven. Even in developed countries, the pr ovision of services is not at all uniform. In the developing world, pediatric pain research is just beginning (e.g. Forgeron et al., 2009). Advances in science have not always result ed in advances in implementation of care. Th ere were signifi cant landmark events that led to the modern era of pediatric pain. Th is treatment appears to facilitate the smooth maintenance of anesthesia, and would seem to be desirable if respiration is not to be aided or controlled. It does, however, make the induction of anesthe- sia by inhalation agents \200\224a tedious process at best \200\224a very prolonged procedure. (p. 1421) In his 1960 paper, Jackson Rees discussed in some detail the anaes- thetic complications of pediatric anesthesia such as the tendency for infants under 6 months to become hypothermic in response to anesthesia whereas older infants became hyperthermic. Hypothermia was more readily managed but hyperthermia some- times led to convulsions and death. Ether anesthesia and atropine premedication contributed to this risk. In summarizing his views, Jackson Ree s (1960) wrote: Recurrent pain in children certainly was known and written about earlier (e.g. Matthews, 19 38), but programs of research about pain in children developed primarily in post-war Europe . Th e seminal work in headache was by Bo Vahlquist (Vahlquist, 1955; Vahlquist and Hackzel l, 1949) and later by his prot g Bo Bille (1962) in Sweden. Vahlquist defi ned criter ia for diagnosis of headache in children and presented clinical series and described common features. Bille \200\231s doctoral dissertation, published as a mon- ograph in Acta Pediat rica , was a large-scale epidemiological study of the children of Uppsala. He described the prevalence and cor- relates of migraine and provided a more detailed set of lab studies an d interviews with a subgroup of children who had pronounced migraine. Bille personally foll owed the group of 73 children with pronounced migraine for 40 years (Bille 1997). Th is wor k was foun- dational for all subsequent studies of migraine and other headaches in children and adolescents. Th e respiratory defi ciencies of the infant during early life and the haz- ards of hyperth ermia in older children suggest that controlled ventila- tion during the maintenance of ane sthesia has special advantages. It should be regarded as an essential part of the technique for prolonged operations, and is highly desirable for shorter procedures. Anesthesia can b e maintained at very light levels with nitrous oxide-oxygen and a relaxant drug, with the r esult that recovery is rapid. \200 Th ere are, therefore, cogent practical and theoretical reasons for maintaining anesthesia with controlled ventilation, a relaxant drug, nitrous o xide and oxygen. (p. 138 \200\223139) John Apley and colleague (Naish and Apley, 1951) in Bristol, England, published epidemiolog ical research on recurrent limb pains demonstrating that about 4% of children had such pain . Th is paper was followed by his groundbreaking epidemiologi- cal and aetiological studies on recurrent abdominal pain (Apley, 1959). Apley found that recurrent abdominal pain was c ommon, aff ecting10.8% of children. Girls were more likely to have recurrent abdominal pain than boys. He linked recurrent abdominal pain to psychosocial problems and argued that ove rmedicalization of recurrent pain led to long-term consequences. Apley \200\231s studies st ill inform our understanding of recurrent limb and abdominal pain. While these studies on r ecurrent pains in children were well known in the pediatric literature, and stimulated clin ical practice, they did not trigger much systematic research interest until the 1980s. Although Jackson Rees is said to have introduced nitrous oxide and oxygen anesthesia withou t ether, it had already been in use for some years in the US by some physicians. Mary Botsf ord in San Francisco (1935) reported using this preparation over a 2-year period for childr en from 1 month to 4 years of age for procedures of 4 minutes to 1 hour and 40 minutes. How ever, for the young- est infants, Botsford regarded ether as the anesthetic of choice. Bots ford also noted that by the 1930s, chloroform had been almost completely discontinued for i nfants and children because of delete- rious eff ects on the liver, cardiac depression, and postoperative aci- dosis. In the discussion section of Botsford \200\231s paper, where res ponses were provided from colleagues, two writers, Weeks and Delprat, commented, \200\230W e are glad to see that she still allows us to use ether in babies, even though she so stron gly favors nitrous oxid[e] and oxygen \200\231. Weeks and Delprat maintained that for abdom inal surgery nitrous oxide and oxygen provided too little relaxation of the tis- sues, and they were prepared to risk a less safe anesthetic (ether). Nitrous oxide and oxygen anesthe sia with a muscle relaxant was considered for many years a light anesthetic that was suffi cient for many pediatric procedures. It appeared to reduce a number of surgical risks, espe cially for infants, based on the knowledge in this period of the physiology of infants and children. Although there were some eff orts to understand the responses of the paediat- ric patient to surgical procedures, evidence of informed decision- making was typically on the basis of published clinical series. Such papers provided clinical information but very lim ited data about an infant \200\231s physiological stress response to invasive procedures. P ediatric pain research during this period was limited and focused on the fi rst epidemiolog ical studies and not clinical care. In 1965, Melzack and Wall introduced an imaginative and com- prehensive theory, known as th e gate control theory of pain, to account for horrifi c injuries that sometimes were not fe lt as pain, and minor injuries that were sometimes felt as severe pain. Th ey used recently discovered physiological data and clinical data to suggest that a mechanism in the substan tia gelatinosa of the dorsal horn of the spinal cord gated sensations of pain from pain rec ep- tors before they were interpreted or reacted to as pain. Th is theory changed how pain was conceptualized and united clinical observa- tions with physiology. Although not specifi cally describing mecha- nisms of action for the role of attention, thoughts, and emotions in pain, Melzack and Wall included these phenomena by hypoth- esizing a central control tri gger that could mediate specifi c central activities. Th e development of modern models of pain increased interest in pain research and in the integration of clinical observa- tion w ith the biology of pain. But drawing attention specifi cally to pain in children did not come easily. Interest was s poradic and research still almost non- existent. Jo Eland was the fi rst North American cli nician scientist to bring pain in children to the forefront. In 1971, she was a faculty Scienti \201 c approaches to pain in children Th e second half of the twentieth century ca n rightly be considered the modern era of pediatric pain research and management. Major CHAPTER 1 history of pain in children 7 member supervising students on a pediatric oncology unit in Omaha, Nebraska. Children were typically diagnosed late, received ineff ective treatment, and died in pain with little pai n relief. In her President \200\231s Message at the American Society of Pain Management Nur ses in 2012, Eland said of this experience: methods of measuring hormonal stress responses using very small samples of blood (Anand et al., 1985). He then demonstrated in clinical series and well-controlled, randomized trials, that term and preterm neonates mounted a major stress response following sur- gery for pat ent ductus repair (Anand and Hickey, 1987; Anand et al., 1987, 1988, 1990). Th ese studies showed that neonates receiving minimal anesthetic, the \200\230Liverpool \200\231 techniqu e that had been stand- ard care since the 1950s, compared to neonates receiving halothane a nesthesia, had signifi cantly elevated levels of plasma epinephrine, norepinephrine, cortis ol, glucagon, beta endorphins, and insulin, and as well as increased mortality in the posto perative period. Watching so many children die in unrelieved pain caused me to begin reading everything I co uld about pain and soon found there was virtually nothing written about pediatric pain. Th e memories of so many children dying in unrelieved pain left a lasting impres- sion that ha s never left me. (Reproduced with kind permission of Jo Eland) Eland and Anderson (1977) noted that only 33 scientifi c articles had been published on pai n in children by the mid 1970s and most of these papers were on pediatric recurrent pain. T h eir own impor- tant contribution to pediatric pain was a comparative chart review of the pain relief given to adults and children following similar surgical procedures. In the revi ew of 25 children, aged 4 \200\2238 years, 21 children had been ordered analgesics but only 12 received any medication. Eighteen of the children were then matched with adults receivi ng similar surgery. Th e adult group were given 372 opioid analgesic doses and 299 non-opio id pain doses. Th ere were meth- odological limitations to this review as a study: it was n ot experi- mentally well controlled, it used questionable matching, and did not measure pai n. It is unknown whether the data from the adult sample came from a similar time period to that of the children or from the same institution. Nevertheless, the diff erence in the pro vi- sion of pain relief between child and adult patients was startling and overwhelming in illustrating that children and adults were not treated similarly for pain. Th is study trig gered two methodo- logically superior studies with similar though less extreme results. Bey er and colleagues (1983) compared 50 children with 50 adults on the postoperative analgesia they received following similar car- diac surgeries. Th e only patients who were not presc ribed any anal- gesics at all were six children. Overall children received less than 50% of the analgesic doses given to adults. Schechter et al. (1986) reviewed charts for the posto perative analgesics received by 90 chil- dren and 90 adults who were randomly selected and matched for sex and diagnosis. Adults received an average of 2.2 doses of opioids narcotics per day, whereas children received half this amount. It is unknown whether the children in these studies were in more pain than adults, as pain was not measured. Nevertheless, these three studies critically established that children \200\231s pain was signifi cantly under treated in hospitals. Anand \200\231s research was well received in the academic community. Anand won the 1986 Dr Michael Blacow prize for the best paper by a trainee at the annual meeting of the British Pediatric Society (Royal College of Pediatrics and Child Health, n. d.). For the pub- lic, the realization that infants were exposed to surgery with mini- mal anesthesia came as a pr ofound shock and was met with initial disbelief. In the media, Anand was viciously attacked in the Daily Mail (UK newspaper) in a story titled \200\230Pain killer shock in babies op eration \200\231 ( Daily Mail , 1987). Anand and colleagues were accused of experimenting o n babies by withholding anesthesia. Th e All Party Parliamentary Pro Life Group demanded th at the General Medical Council investigate these experiments. Many distinguished medi- cal scientists insisted that these studies were ethical, and methodo- logically rigorous challe nges of then current standard of anesthetic procedure for infants undergoing surgery, and w ould lead to better care. In 1988, Sir Bernard Braine, head of the All Party Group pub- lic ly apologized for his accusations (Anonymous, 1988). Th e second seminal event was related to Anand \200\231s work but occurred in the US and wa s not research but one family \200\231s experi- ence. Like Anand \200\231s research, the st ory of Jeff rey Lawson focused on neonatal anesthesia and it too was debated in the public arena through the media. Jeff rey Lawson was born in February 1985, at 25 \200\22326 weeks gestational age, weighing 760 grams, and was admitted to the Washington National Children \200\231s Hospital for treatment of patent ductus arteriosus \200\224a not uncommon prob- l em in a premature infant. Th e ductus arteriosus is a blood vessel that permits blood to ci rculate through the baby \200\231s lungs before birth, closing a few days aft er birth. A p atent ductus arteriosus leads to abnormal blood fl ow between the aorta and pulmonary arter y, two major blood vessels that carry blood from the heart. Aft er some medical attempts to correct this condition, Jeff rey Lawson underwent open heart surgery to correct this abnor mal- ity. His mother described Jeff rey \200\231s anesthesia during the surgery in this way : Along with these early studies which identifi ed the problem of recurrent pains, abdominal pain, and headache in childhood, and undertreatment of postoperative pain in children, work was begin- ning to untangle the cry of infants, crying long being regarded as symptomatic of pain and distress in infants. In the 1960s, auditory and spectographic cry analysis of i nfants was systematized by Ole Wasz-H ckert and colleagues in Finland (Wasz-H ckert e t al., 1968). Th is work was sophisticated and well respected, and dealed with pain and oth er types of cries, but did not infl uence the investi- gation of pain outside of cry analys is. Jeff rey was awake through it all. Th e anesthesiologist paralyzed him with pavulon, a drug that left him unable to move, but totally con- scious. When I questioned the anesthesiolog ist later she said Jeff rey was too sick to tolerate powerful anesthetics. Anyway, she said , it had never been demonstrated to her that premature babies feel pain. (Lawson, 1986, pp. 124 \200\223125) Following surgery, Jeff rey went into shock, catabolized, and suf- fered heart, kidney, and liver failure. He died on 31 March 1985, 5 weeks following surgery. Ms Lawson contacted ma ny professional and social service agencies and other individuals to support her belief tha t babies should receive pain control for surgical proce- dures before her story was picked up by the media. Th e most seminal developments to draw attention to pain in infants and children were two e vents in the 1980s. Th e fi rst was a series of studies by Kanwaljeet Singh Anand as a PhD student at Oxford University. With support from a Rhodes Scholarship and the John Radcliff e Hospital, Anand began one of the fi rst research programs on pain in neonates. Anand deve loped sophisticated In writing the story of Jeff rey Lawson for Th e Washington Post , Sandy Rovner quoted Will is McGill, Chair of Anesthesia at the SECTION 1 introduction 8 Children \200\231s Hospital National Medical Center. Dr McGill asserted that there were ris ks with anesthesia and that \200\230it doesn \200\231t do any good to have a dead patient who doesn \200\231t feel pain \200\231 (Rovner, 1986, p. 7). Th e article in Th e Washingto n Post triggered other coverage emphasizing that babies were undergoing surgery without ana es- thesia. Th e American Society of Anaesthesiologists (1987) and the American Academy of Pediatrics (1987) asserted that anaes- thesia should not be routinely withheld from neonate s. In 1996, the American Pain Society established the Jeff rey Lawson Award for Advocacy in Children \200\231s Pain Relief to honor Jeff rey Lawson and the contribution of his mother to the advancement of pain in infants and children. Th e Anand story in England and the Lawson case in the US were compelling. Th ey were follo wed by a dramatic increase in profes- sional and scientifi c interest in pain in children. Between 1981 and 1990, there were 2966 articles on pediatric pain with a striking increase occurring in the 1980s (Guardiola and Ba os, 1993) and an upsurge in articles on pain in neonates (Ba os et al., 2001). Books on some specifi c pains in childhood, such as Aple y \200\231s book on abdominal pain (1959), had already appeared, but now, the fi rst books covering the broad area of childhood pain were published (Table 1.2 ). Most of these books have been directed to health pro- fessionals but some focused on helping parents to manage their children \200\231s pain (Table 1.3 ). Table 1.2 Books for health professionals on pain in infants, children, or adolescents Author(s) Title Year Ross and Ross 1988 Childhood pain: Current issues, research and treatment McGrath 1989 Pain in children: Nature, assessment, and treatment Schechter and Berde 1993 Pain in infants, children and adolescents Kuttner 1997 A child in pain: How to help, what to do Yaster et al. 1997 Pediatric pain management and sedation handbook Finley and McGrath (eds) 1998 Measurement of pain in infants and children Dahlquist 1999 Pediatric pain management Finley and McGrath 2001 Acute and procedure pain in infants and children Anand et al. (eds) Pain in neonates and infants (three editions) 2002, 2004, 2007 McGrath and Finley 2003 Pediatric pain: Biological and social contexts Tobias and Deshpande Pediatric pain management for primary care (2nd edn) 2004 Finley et al. (eds) 2006 Bringing pain relief to children: Treatment approaches Oberlander 2006 Pain in children and adults with developmental disabilities Rogers 2008 Managing persistent pain in adolescents Walco and Goldschneider (eds) 2008 Pain in children: A guide for primary care Twycross et al. (eds) 2009 Managing pain in children Kuttner 2010 A child in pain: What health professionals can do to help McClain and Suresh (eds) 2011 Handbook of pediatric chronic pain: Current science and integrative practice Oakes 2011 Compact clinical guide to infant and child pain management: An evidence-based approach for nurses Chambers et al. 2012 Pediatric pain: A clinical casebook Palermo 2012 CBT for chronic pain in children and adolescents Table 1.3 Books for parents on managing children \200\231s pain Author(s) Title Year Finley and Turner 1992 Making cancer less painful: A handbook for parents McGrath et al. 1994 Pain, pain go away: Helping children with pain Kuttner 1997 A child in pain: How to help, What to do Krane and Sinberg 2005 Relieve your child \200\231s chronic pain: A doctor \200\231s program for easing headaches, abdominal pain, \201 bromyalgia, juvenile rheumatoid arthritis, and more Zeltzer and Schlank 2005 Conquering your child \200\231s chronic pain: A pediatrician \200\231s guide to reclaiming a normal childhood CHAPTER 1 history of pain in children 9 Th e International Association for the Study of Pain established a Special Interest Group o n Pain in Childhood (<http://www.child- pain.org>) in the 1980s. One of its activities is t he International Symposium on Pediatric Pain (<http://childpain.org/ispp.shtml>), the fi rs t was held in Seattle in 1988. Th e PEDIATRIC-PAIN elec- tronic discussion list began in th e 1990s (PEDIATRIC-PAIN@ lists.dal.ca>). At present it has over 800 members and remains an active discussion forum. Th e Pediatric Pain Letter (<http://www. childpain.org.ppl>) began in 1996. Th e International Pediatric Pain Forum is another pediatric pain meeting. It is held every 2 \200\2233 years on a focused theme (<http://pediatric-pain.ca/content/IFPP>). on children \200\231s pain in the Western world. Recently, researchers have come to recogni ze that the pain of children in underdeveloped countries is even more greatly challenged by the lack of educa- tion about child pain and limited or no access to appropriate pain mana gement.