Introduction Th ere is an enormous amount of scientifi c data about pain but com- parativel y little knowledge specifi c to children with intellectual or developmental disability. A P ubMed search using the terms \200\230pain \200\231 and \200\230human \200\231 yielded ove r 100 000 publications for the 5-year period between 2005 and 2009 (the last full 5-year ep och) or, approximately 20 000 papers per year reporting on new discoveries, reviews, and th eories regarding pain and the human condition. Only a fraction (3.7%) of those papers addre ssed pediatrics and pain (the topic of this volume). For that same 5-year period, there wer e a total of 30 scientifi c papers published specifi c to pain and children with I/DD \200 \224approximately 0.03% of the publication volume. Considering that approximately 1% to 7% of the world \200\231s population lives with an intellectual or related developmental disab ility (estimates vary widely between developed and developing countries; World Health Organ ization, 2001), the gap between what science has to tell us about pain in this population a nd what we probably need to know is striking (Figure 16.1 ). A contributing factor for this paucity of literature is most likely the routine exclusion of individuals with I/DD from r esearch. Th e majority of scientifi c activity devoted to pain and children with I/DD in the previou s decade has been to \200\230build a better mousetrap \200\231 \200\224 improving behavior al assessment techniques to identify accurately the presence of pain and its source or type , when reliable self-report is not an option. Th e fruits of this labor are manifest in sev eral rating scales and questionnaires designed to measure pain intensity/sever- ity and its expression (these are reviewed in detail in later sections). Although the terms intellectu al disability and developmental dis- ability are familiar ones, we encourage the reader to pay careful attention to the explanation of these terms. Th e term I/DD includes a populati on of children that is highly heterogeneous: children with conditions of diverse type and e tiology (e.g. Down syndrome, cer- ebral palsy (CP), Rett syndrome) are included along with children with neurodevelopmental disabilities of unknown origin. Th erefore our attempt her e is to portray common features related to pain expe- rience and management that are found across this diverse group, and specifi cally within certain subpopulations. By the very nat ure of their underlying condition children with I/DD are particularly at risk for painful e xperiences disproportionate to their typically developing peers. Common vulnerabilities chi ldren with I/DD face SECTION 4 pain in specific populations and diseases 148 in intellectual functioning and in adaptive behavior, which covers many everyday social and practical skills. Th is disability originates before the age of 18 \200\231 (2012). Simila rly, the International Association for the Scientifi c Study of Intellectual Disability (IA SSID) considers ID as a \200\230signifi cant intellectual defi cit present from birth, or which originates at an early age or during the developmental period \200\231 (2012). Th ere are key components to the defi nitions specifi c to the concept of \200\230intellectual f unctioning \200\231 and \200\230adaptive behavior \200\231. Intellectual functioning (i.e. intelligence) \200\230refers to general mental capacity, such as learning, reasoning, pro blem solving, and so on. One criterion to measure intellectual functioning is an IQ test. G enerally, an IQ test score of around 70 or as high as 75 indicates a limitation in intel- l ectual functioning \200\231 [i.e. greater than two standard deviations below average IQ] (A AIDD, <http://www.aaidd.org/content_100.cfm>). A similar approach is used to determine adap tive function. Specifi cally, standardized tests are used to determine limitations in adapt ive behavior, comprised of three specifi c skill types includ- ing conceptual skills (e.g. number concepts), social skills (e.g. social problem solving), and practical skills (e.g. a ctivities of daily living). On the basis of a set of standardized measures designed to spec ifi - cally assess and evaluate intelligence and adaptive behavior it is determined whether a child has an ID (see Salvador-Carrulla et al. 2011 for an interesting discussion of ID i n the medical context.) (a) 90,000 80,000 70,000 60,000 50,000 40,000 30,000 20,000 10,000 0 Pediatric Pain Pediatric Pain \200\230Plus \200\231 Pain Human 1960 \200\22364 1975 \200\22379 1965 \200\22369 1970 \200\22374 1980 \200\22384 1985 \200\22389 1990 \200\22394 1995 \200\22399 2000 \200\22304 2005 \200\22309 (b) 4,500 4,000 3,500 3,000 2,500 2,000 1,500 1,000 500 0 Pediatric Pain Pediatric Pain \200\230Plus \200\231 De \201 ning developmental disability Developmental disability as defi ned in the US by th e Developmental Disabilities Assistance and Bill of Rights Act (DD Act; PL. 98 \200\223527) refers to a \200\230severe, chronic disability \200\231 attributable to \200\230mental \200\231 and/or \200\230physi- cal \200\231 impairments that are \200\230likely to contin ue indefi nitely \200\231, resulting in substantial functional imitations in three or more \200\230major life activity areas: self-care, receptive or expressive language, learning, self-direc- tion, capacity for independent living and economic self-suffi ciency \200\231, are manifest by age 22 and require care, treatment or other services of lifelong extended d uration. Some conditions may be included cat- egorically, e.g. CP, spina bifi da, autism. I t is worth noting that unlike \200\230intellectual disability \200\231, classifying develo pmental disability does not benefi t from a prescribed set of standardized assessment instr uments, procedures, or professional training programs. From a somewhat similar perspective, through the World Health Organization (WHO), Th e International Classifi cation of Functio ning, Disability and Health (referred to as ICF) also provides a classifi cation system for health and health-related domains aff ected by disability. Th e domains are clas- sifi ed from body, individual and societal perspectives in two areas; (1) body functions and struct ure, and (2) activity and participation. Th e ICF is WHO \200\231s framework for measuring health and disability at both individual and population levels. 1960 \200\22364 1965 \200\22369 1970 \200\22374 1980 \200\22384 1985 \200\22389 1990 \200\22394 1995 \200\22399 2000 \200\22304 2005 \200\22309 1975 \200\22379 Figure 16.1 Cumulative frequency of pediatric pain research based on PubMed search results for full 5-year epochs using search terms \200\230pain \200\231, \200\230human \200\231, \200\230pediatric \200\231, and \200\230pediatric \200\231 plus \200\230intellectual dis ability \200\231, \200\230mental retardation \200\231, \200\230developmental disability ( a) and results for \200\230pain \200\231, \200\230pediatric \200\231, and \200\230pediat ric plus \200\231 only (b). with respect to pain include increased prevalence of painful condi- tions, both acute and c hronic, higher rate of exposure to painful procedures (diagnostic and therapeutic), and neu rosensory con- cerns that heighten the pain experience as well as complicate pain assessmen t and management. Pain concerns are usually fi rst addressed in a medical context. An initial obstacle health care providers (HCPs) oft en face when providing care for children with I/DD is the incons istency and lack of detail typically found in medical records regarding a child \200\231s n eu- rodevelopmental disabilities. While school records may contain the results of extensive neurodiagnostic testing, medical records oft en lack key information regarding the child \200\231s specifi c cognitive, communication, and adaptive behavior abilities. Th is can ma ke it extremely diffi cult for the HCP to establish the specifi c neurodevel- opmental stat us of a child with I/DD (Salvador-Carulla and Saxena, 2009). HCPs are left to guess or make assumptions based on \200\230clues \200\231 such as observed communication patterns and b ehavior. Medical records frequently include non-specifi c use of terms like autistic , ment ally retarded , or developmentally delayed . Used appropriately, the term developmental del ay fl ags neurodevelopmental concerns in young children. However, this term is oft en inclu ded in the medical record of older children, even adults, when no more specifi c devel- opm ental descriptors have been established in the medical record. Issues for I/DD created by the de \201 nition of pain Pain, as defi ned by the Internation al Association for the Study of Pain (IASP), refers to \200\230an unpleasant sensory and e motional experi- ence associated with actual or potential tissue damage, or described in te rms of such damage \200\231 (Merskey and Bodguck, 1994). Because of problems created, in pa rt, with the implicit requirement to self-report on the sensory or emotional experience, th e defi nition was revised in 2002 with the clause \200\230the inability to communicate ver bally does not negate the possibility that an individual is experiencing pain and is in nee d of appropriate pain-relieving treatment \200\231 (IASP, 2012). Th e overwhelming approach to considering pain, however, still relies extensively on self-report using language based on the spoken word (despite problems associated with almost exclusive reliance on De \201 ning intellectual disability Intellectual disability (ID; previously referred to a s \200\230mental retarda- tion \200\231 and referred to as \200\230learning disability \200\231 in the UK) is defi ned by the American Association on Intellectual and Development al Disabilities (AAIDD) as a \200\230disability characterized by signifi cant limitations both CHAPTER 16 pain in children with intellectual or developmental disabilities 149 self-report as a \200\230gold standard \200\231; see Schiavenato and Craig, 2010). Th e ob vious problem created by the original defi nition for children with I/DD is that diff erent combinations and functional levels of language/communicative, motor, and cognitive impairm ents asso- ciated with I/DD make self-report of a complex experience such as pain diffi cul t if not impossible for some children. Th ere is a likeli- hood that pain among many of the se children cannot be measured in conventional ways (or perhaps even detected), resulting i n pain- ful conditions that are untreated or undertreated. aware of the fact that there are rare syndromes and conditions in which pain sensitivity is reduced or absent or that pain is sensed but the individual is indiff erent to it (Nagasak o et al., 2003).) Epidemiology Most children with I/DD have associated disabilities and chronic health condit ions; the likelihood of these conditions increases with the severity of the disability, as does the frequency of painful pro- cedures for diagnostic or therapeutic indications. Th er e are several reasons that children with I/DD are at higher risk for experiencing recurrent pain than their peers without disability, including pain- ful conditions associated with t he underlying cause of the disabil- ity; higher rates of painful medical procedures; physic al therapy regimens that might be painful; impaired cognitive or communi- cation abilities, resulting in under-recognition or delay in recogni- tion that the individual is experienci ng pain; and nociceptive pain experienced for extended periods of time increasing the risk of developing neuropathic pain or other chronic pain states. Historical perspectives on pain and I/DD Historically, there has been little recognizable s ustained scientifi c investigation of pain among individuals with I/DD. At the same time, t here is a long history of quasi-scientifi c perspectives regard- ing individuals with I/DD, including children, to be \200\230defective \200\231 in sensory function, particularly to uch (including the ability to dis- criminate pain). So much so, as Sobsey (2006) points out , that the early tests for intellectual ability relied heavily on sensory discrimi- nation tasks as well as notions of \200\230defects of vitality \200\231 and \200\230energy \200 \231. In his early account of autism, Bettelheim (1967) remarked that: Th ere is very limited scientifi c evidence describing the incidence or prevalence of pain among the general population of children with I/DD. In daily pain diaries recorded by paren ts of non-verbal chil- dren with severe cognitive impairments over 2 weeks (n = 34), 73% of the children had a painful experience on at least 1 day (Stallard et al., 2001) In a longi tudinal study, children with moderate to pro- found ID (n = 94) were found to experience pa in for an average of 9 h per week (Breau et al., 2003b). Most of the painful events were no n- accidental and were not associated with medical procedures but were related to gastroint estinal or musculoskeletal problems. Th e limited available evidence supports a reasonable assumption that individu- als with more signifi cant impairments of cognition and communica - tion are more vulnerable to experiencing painful events that are not recognized or adequa tely managed. For example, although a parent might recognize that the child is experiencing pain, the child might not be capable of providing key descriptive information regarding th e location, type, or timing of the pain. Recurrent, pervasive pain experienced by these chi ldren can result in extensive suff ering and limitation. For example, ongoing pain issues h ave been associated with sleep problems of both the child and the family (Breau and Camfi e ld, 2011; Hemmingsson et al., 2009). Why these children are so unresponsive to physical pain is diffi cult to know. It is the mo re baffl ing because they seem to pay so little atten- tion to the external world and to di rect all their attention to them- selves. Th us, \200 they should be more sensitive to wh at comes from inside them, including pain, than are normal people. But actually, the opposi te is true. (pp. 58 \200\22359) Th e historical lack of scientifi c attention given to the issue of pain in children with I /DD may be, in part, due to longstanding cul- tural \200\230norms \200\231 and personal be liefs, held by some and refl ected in Bettleheim \200\231s thinking, that people with I/DD do not feel pain (insensitive) or do not care about pain (indiff erent) (Couston, 1954; Sob sey, 2006). From this perspective, it follows logically that pain thresholds among individu als with I/DD would be expected to be elevated. Further, this view would suggest that indiv iduals with I/DD who experience noxious stimuli would have reduced pain sensation compared to comparable peers (age, gender) without disabilities experiencing the same degree of noxi ous stimulation. Th e problem with this view \200\224which has persisted to the present in diff erent forms (Malviya et al., 2005) \200\224is that studies are rarely designed explic- itly assessing the dimensions considered to be defi cient (e.g. pain thresholds). As a con sequence, there is a scientifi c vacuum concern- ing the state of our knowledge about senso ry function in relation to pain experience among individuals with I/DD (see Defrin (2004) f or an example of a threshold study specifi c to I/DD). Th e population of children with I/DD is extremely heteroge- neous with regard to underlyin g conditions, degree of disability, functional limitations, etc. It is not surprising, then , that the lit- erature addressing pain prevalence among children with I/DD in recent years includes papers on specifi c disabilities. For example, in the single study exploring pain among children with spina bifi da (n = 68), 49% reported experiencing pain weekly or more frequently (Clancy et al., 2005). Considering the core defi nition of pain, the revision notwith- standing, there is a danger that the \200\230elevated thresholds \200\231 viewpoint (either pain insensitive and/or p ain indiff erent) as the only posi- tion regarding pain may persist for children with I/DD. Th is may be particularly true for those children with multiple impairments (intellectual, motor, communicative) resulting in severe or pro- found disability \200\224because of the great diffi culty in reliable access to a subjective state (Breau et al., 2003a; Symons et al., 2008). Caregivers and healthcare professionals oft en report that pain signs are ambig uous, paradoxical, altered, blunted, or that they confuse pain signs with stress or arousal (Oberlander and Symons, 2006). Although there is great heterogeneity within the population of chil- dren with I/DD and some individuals may experience altered pain sensation (simila r to the general population), there is no current compelling reason to think that all child ren with I/DD would have such wholly aff ected nociceptive physiological systems. (We are Down syndrome From 40% to 60% of children with Down syndrome have congeni- tal cardiac or i ntestinal anomalies requiring surgical intervention, and are therefore exposed to pain asso ciated with major invasive procedures (Valkenburg et al., 2010). Later in life, children wi th Down syndrome are at risk for orthopedic problems associated with pain. Quantitative sen sory testing studies in adults with Down syndrome have shown that the response time to sens ory stimuli is prolonged, localization is more diffi cult, and that adults with Down syndro me are possibly more sensitive to heat pain (Defrin et al., 2004; Hennequin et al., 2000). SECTION 4 pain in specific populations and diseases 150 Cerebral palsy Recent population-based investigations place estimates of the prev- alence o f recurring pain among children with CP at between 50% and 75% (Doralp and Bartlett, 2010; Parkinson et al., 2010; T z n et al., 2010). Th e most common type of pain among chil dren with CP is musculoskeletal pain. In addition, mobility limitations can result in secon dary conditions that also cause signifi cant pain, including pressure ulcers and constipati on. Th e most common sites of pain include feet, legs, back, hips, hands, and arms (Engel e t al., 2005). Children with CP oft en have low bone mineral density (attribut- able to limi ted weight-bearing, seizure medications, and other risk factors) which contributes to high fracture rates (Stevenson et al., 2006). It is important to note the heterogeneity of the p opulation of children with CP, especially with regard to level of physical and cognitive li mitations. used with great caution and in conjunction with other types of pain indicators (Breau and B urkitt, 2009; Breau et al., 2007). Rating scales by proxy To gain access to the pain condition when self-report has not proven reliable, observational methods have been used. Observational pain scales have been create d based on measuring times when children are presumed to be in pain (e.g. during a needle s tick, postopera- tive) versus times when children are not suspected to be in pain and exami ning behavioral cues that diff er between the two conditions (Symons et al., 2008). A secon d approach has been to generate pain inventories or checklists based initially on interview s with caregiv- ers that resulted in determining a list of pain cues. Th e initial lists ar e then reduced via item analysis and a rating scale is developed that in turn can be valida ted with diff erent samples (Breau et al., 2002; Duivenvoorden et al., 2006; Hunt et al., 2 004) Although CP is oft en described in terms of motor impairments caused by anomalies in the br ain, it is important to consider that the somatosensory system is also involved. Th e inter play between altered sensory functioning and pain experiences in individuals with CP has be en increasingly recognized in a variety of conditions such as entrapment neuropathy (Frasca relli et al., 2005) or by apply- ing sensory testing techniques (Riqueleme and Montoya, 201 0) or related approaches to investigating sensory issues (Riqueleme et al., 2011). Although not all children with CP experience pain rou- tinely, those who do are at risk for experie ncing painful conditions through adulthood (Castle et al., 2007). With modern advances in m edical management children with CP can be expected to live as long as their peers without d isability (Strauss et al., 2007). Th e types of pain experienced in adulthood are likely to be associated with lifelong strain on muscles and joints (Turk, 2009). In multiple empirical studies there have been reports on the development of measurement too ls that produce valid and reliable pain scores for children with I/DD (Breau et al., 2002; Hunt et al., 2004; Malviya et al., 2006). Th ese measures focus on vocalizations, facial ex pression, physiological changes, and social changes. Each scale is unique (e.g. number of i tems, scoring method) but all share fundamentally similar pain descriptors. Th ree of the m ost promis- ing pediatric pain measurement scales (NCCPC-R, PPP, r-FLACC) are reviewed in T able 16.1 (space precludes reviewing all relevant pediatric pain I/DD scales \200\224see al so Valkenburg et al. (2010) for a comprehensive scale review). It is important to acknowled ge that it is sometimes diffi cult to distinguish pain from other responses such as fear, a nxiety, sadness, or even contentment or excitement. Work continues with the emerging measur ement tools to distin- guish specifi c cues related to pain to provide a more clear under- standing of when a child with I/DD may be experiencing pain. Th e scales have face validity , some empirical validity, and perhaps also clinical utility. All pain observation scales a ssess similar pain cues and all reviewed here have shown promising reliability and valid- i ty when used with children with I/DD (Breau et al., 2002; Hunt et al., 2004; Malviya et al. , 2006). A diff erent approach \200\224used so far with adult samples with I/DD \200\224dev eloped by Bodfi sh et al. (2001; Phan et al., 2005) was to base the scoring of a scale on a standard- ized pain exam procedure. Th e most important choice particularly from a clinica l perspective may not be which scale to use but rather to make a decision that pain will be assessed systematically and be aware that there are multiple measurement tools to choose f rom. Assessment Reliably and validly assessing a complex construct like pain is fraught with cha llenges. Th ere is no equivalent of a \200\230pain ther- mometer \200\231 and the diffi cu lty of the task, already made diffi cult in a pediatric setting, is amplifi ed in the prese nce of a cognitive, communicative, or motor impairment associated with I/DD. As such, the v erbal and cognitive functioning relied on for self-report of pain is compromised. Part of t he challenge is also in the varied nature of I/DD. Th ere are multiple levels of cognitive functioning, verbal abilities, physical and motor impairments such that no one assessment a pproach fi ts for all children with I/DD. Further, there are oft en multiple people involve d in the care of children with I/DD (e.g. parents, teachers, physicians, nurses, physical t herapists, etc.) and so pain assessment and management may oft en be regarded as someone el se \200\231s responsibility. Treatment Adequate pain management in children with I/DD is accomplished when one fi nds a balance between caring for the individual and seeing the broad picture of analgesic managem ent and pain mecha- nisms. As already described, these children are more at risk to experie nce acute and chronic pain. Comorbidities can cause pain and their treatment can infl uence pain management. Caregivers in all disciplines should select the most appropriate and adeq uate pain management for the individual. Pain expression could be less apparent than in oth er children, but that is not necessarily a good reason to delay analgesia. Unfortunately, w ith the paucity of evidence on pain management in this heterogeneous popula- tion, the broa d picture in terms of evidence-based practice is not yet very clear. Th e starting point sh ould be treatment according to Self-report Self-report is considered the \200\230gold standard \200\231 for pain assessme nt in other populations, however there is little evidence supporting its use with children with I/DD (Breau and Burkitt, 2009). For instance, Benini et al. (2004) taught children wit h I/DD on how to use self-report tools and then asked them to self-report on their own pain intensity and location following immunization. Despite having done well during training, o nly half of the children with I/DD were able to give consistent and accurate self-reports o f their pain. Given the disparity between reporting pain during practice and during a real painful event, self-report is recommended to be CHAPTER 16 pain in children with intellectual or developmental disabilities 151 Table 16.1 Sample pediatric pain assessment tools designed for intellectual and development al disabilities Pediatric Pain Pro \201 le (PPP) Non-Communicating Children \200\231s Pain Checklist-Revised (NCCPC-R) Faces Legs Activity Cry Consolability Scale \200\224Revised (r-FLACC) Purpose Th e purpose of the PPP is to provide an individualized measure for each child that is asse ssed. Th is scale is unique in that it asks caregivers to describe their child \200\231s go od days and bad days Th e purpose of the NCCPC-R is to provide one tool that is useful and accurate for all non- verbal children with IDD. Th e NCCPC-R quanti \201 es pain responses observed by clinician s, parents, and caregivers regardless of how well they know the child. A postoperative vers ion is available Th e purpose of the r-FLACC is to provide a feasible method of quantifying an individual ch ild \200\231s pain based on \201 ve domains and the speci \201 c criteria for scoring ea ch of those domains. Th e original FLACC was revised to expand the descriptors for the subs cales that were least reliable when used with children with IDD Description of subscales and items Th e PPP is a semi-individualized measure that allows caregivers to describe their child \200\231s behaviors related to pain. It also includes a 20-item questionnaires that is scor ed on a 0 \200\2233 scale Th e NCCPC-R includes seven subscales (vocal, social, facial, activity, body and limbs, phy siological, and eating/sleeping) each of which include multiple items that are scored from 0 \200\2233. Th ere are a total of 30 items. Th e NCCPC postoperative version includes 27 o f the same items but excludes the eating/ sleeping subscale Th e r-FLACC has \201 ve items (Face, Legs, Activity, Cry, Consolability) that are each s cored from 0 \200\2232 based on the detailed descriptors speci \201 c to each item. Th e r -FLACC also provides caregivers the opportunity to write in other pain descriptors that may be unique to their child Scale format Estimated time to complete: 5 \200\22310 min Scoring: add item scores to determine a total score. Th e information written in by caregivers cannot be scored but provides valuable inf ormation speci \201 c to that child Estimated time to complete: requires a 5 \200\22310-min observation period and <1 min to sc ore. Scoring: item scores are added to determine the total score. A total score of 7 or gre ater indicates the child is in pain (accurate 77% of the time), and a score of 6 or less su ggests the child does not have pain (accurate 84% of the time) Estimated time to complete : 1 \200\2232 min Scoring: a total score of 0 \200\2233 is mild, 4 \200\2236 is moderate, and 7 \200\22310 is severe pain Psychometric properties Sample used to test psychometric properties: parents reported on 144 non-verbal children wi th various IDD (ages 1 \200\22318). Th e PPP is a valid, reliable, and sensitive measure fo r individual children; however, it does not provide generalizable measures across children because the information written in is unique to each child Sample used to test psychometric properties: Caregivers of 71 non-verbal children with vari ous IDD (ages 3 \200\22317). Th e NCCPC-R shows strong inter-rater reliability and internal consistency. Th is measure has also proved to have consistent scores over time. Th e NCCPC -R is sensitive and speci \201 c to pain and the scores are signi \201 cantly related to parent pain rating Sample used to test psychometric properties: 54 children ages 4 \200\22321 with various IDD pre and post surgery. Th e r-FLACC showed inter-rater reliability and test \200\223retest reliability. Th e measure showed strong correlation between observer FLACC scores and a par ent \200\231s global pain rating Recommendations Th e PPP is useful for distinguishing a Th e NCCPC-R is recommended for use in research studies because it is a standardized scale that is consistent across children. Th e NCCPC-R has shown strong psychometric properties a cross multiple populations and settings and is consistently accurate. Th ere is a required observation time that allows for more accurate assessment because observation is a key part of proxy assessment Th e r-FLACC demonstrates clinical utility as it is fast and easy to use. It can be individ ualized for each child which is bene \201 cial for children with unique pain signs. Becaus e it is individualized it is more di \203 cult to compare across children and to have a co nsistent pain score that serves to determine when a child is in pain or not child \200\231s good days from bad days and it is recommended for monitoring pain over time . Because the PPP provides the opportunity for parents to add detailed information about th e child \200\231s unique pain expression, this scale may be especially bene \201 cial for parents to complete and leave with healthcare professionals during a child \200\231s hospit al stay Where to obtain the scale <http://www.pppro \201 le.org.uk> <http://www.aboutkidshealth.ca/En/ Documents/AKH_Breau_Everyday.pdf> <http://deepblue.lib.umich.edu/ bitstream/2027.42/72254/1/j.1460 \200\223 9592.2005.01773.x .pdf> References Hunt et al. (2002) Breau et al. (2002) Malviya et al. (2006) the WHO guidelines: by mouth, by the clock, and by the ladder (WHO, 1996, p. 36). For the p erioperative setting, the American Society of Anesthesiologists published practice guidelin es for acute pain management, with special recommendations for pediatric and cognitive impa ired patients (2012). Prospective randomized trials on analgesia in children with I/DD are scarce. Lower doses of intraoperative opioids have been observed (Koh et al. 2004; Long et al., 2009). Malviya et al. (2005) reported that 89% of the surveyed physicians had a tendency to prescribe subthe rapeutic doses of analgesics in children with intellectual SECTION 4 pain in specific populations and diseases 152 disability. However, less than 10% of surveyed anesthetists report giving lower doses of in traoperative opioids in children with I/DD (Valkenburg et al., 2012b). From these observati onal studies it is clear that it can be challenging to provide adequate analgesia in this h eterogeneous population, there are concerns about the risk of side eff ects and toxicity, a nd so far there is no proper evidence for dos- ing analgesia in these children. the fi nding that patients treated with antiepileptic drugs required higher doses of fentan yl during general anesthesia (Tempelhof et al., 1990). A survey among Dutch anaesthesiologi sts revealed that around 75% adjust the dose of anesthetic drugs in children treated with a ntiepileptic drugs (Valkenburg et al., 2012b). Th e interaction between antiepileptic drugs and analgesics as well as general anaes- thetic drugs needs further attention. On the positive side, the development of the pain assessment tools for children with I/DD ( reviewed earlier) and the establish- ment of pharmacological research in children will make it feasi- ble to start with pharmacokinetic and pharmacodynamic studies specifi c to child ren with I/DD that, in turn, will provide evidence for decision aids to manage their pain ( Valkenburg et al., 2012a). Walker advocates that pain management is more than the meas- ure ment of pain intensity; it should include a global assessment of inter-related current cond itions and general health, nature of the surgery (if relevant), prior pain experience, curr ent response to analgesia in terms of effi cacy, and side eff ects (Walker, 2012). Pain treatment in cerebral palsy A key component of pain management in individuals with CP is the reduction of muscle spasticity that contributes to musculoskeletal pain. A variety o f therapeutic modalities are used to relieve pain associated with muscle spasticity (Aisen et al., 2011; Roscigno, 2002). Oral antispasticity medications include baclofen, dantro- le ne, diazepam, and tizanidine. Baclofen can also be delivered intrathecally by an implanted pump. Botulinum toxin A is used through multiple injections made to targeted muscle groups, aft er local anesthesia with EMLA and procedural sedation or under general anesthesia (d epending on location of injection, number of muscle groups to be treated, age, comorbiditie s and previous experiences). Th e toxin \200\231s inhibition of the release of acetylcho- l ine at the neuromuscular synapse results in relief of spasticity that lasts 3 to 4 months \200\224and for some individuals there is cor- responding pain reduction. Th rough neurosur gery selective dorsal rhizotomy involves the cutting of sensory nerves to reduce mus- cle s pasms (Grunt et al., 2011). A randomized controlled trial in 27 children with CP showed tha t epidural analgesia can give bet- ter analgesia and less muscle spasms aft er selective do rsal rhizo- tomy than intravenous morphine infusions (Malviya et al., 1999). Non-pharmacolo gical interventions including massage and other interventions are widely reported as eff ec tive in relieving pain and promoting comfort (Glew et al., 2010), though there has been lit tle research-based evidence demonstrating these benefi ts. Pharmacokinetics In general, children with I/DD are at greater risk to develop side eff ect s (Reiss, 1997), but epidemiological data are missing. Case \200\223 control studies have s hown that children and adults with Down syndrome are at increased risk to develop side eff ects and toxicity when treated with paracetamol (Griener et al., 1990) or methotrex- ate (B uitenkamp et al., 2010). Aft er inhalational induction with sevofl urane, bradycardia and h ypotension occurred in 57% of the children with Down syndrome versus in 12% of the children with- out Down syndrome (Kraemer et al., 2010). From observational clinical studies it is clear that there is variability in the dosing of analgesics and there is a high prevalence of comorbidities and treat- ment with psychotropic and anticonvulsant drugs in children wit h I/DD (Valkenburg et al., 2010). For adequate pain management, it would be ideal to predict the pharmacokinetics (what the b ody does to a drug) and pharmaco- dynamics (what the drug does to the body) of the analgesi cs for the individual patient. It would mean that we have knowledge of the pharmacokinetic covariate eff ects (size, age, and organ function) as well as pharmacodynamic covariate eff ects (target organ per- fusion, receptor sensitivity, effi cacy, pharmacogenomic changes). As a group, children with I/DD are at risk for variability in both the pharmacokinetics an d pharmacodynamics, due to, for exam- ple, the use of antiepileptic drugs, cerebral patholo gy, and genetic abnormalities such as trisomy 21. It will be a challenge to focus pharmacok inetic and pharmacodynamic studies on the drugs with the highest priority and the groups of children that are the most at risk for polypharmacy and side eff ects, but understanding o f the factors that contribute to variability will help to individualize pain management. Physical therapy In addition to ID, many children with I/DD have a physical dis- ability. C P causes motor disorders such as an altered muscle tone, impaired postural control, and mus cle synergetic action (Martin et al., 2010). Motor development is oft en delayed in childre n with Down syndrome and they are at high risk for musculoskeletal disor- ders due to joint hypermobility and ligamentous laxity (Weijerman and de Winter, 2010). Physical therapy tre atment goals are aimed at improving muscle strength, range of motion, gross motor func- tio n, endurance, and overall quality of life including pain reduc- tion (Martin et al., 2010; Opheim et al., 2011). A survey among American physical therapists revealed that 80% of the respondents used pain assessment tools in children with I/DD. Distraction, pro- cedural tal k, and praise were the most used pain management tech- niques (Swiggum et al., 2010). Physi cal therapy will be used to treat and prevent pain from musculoskeletal disorders, but the therapy can be painful itself. Pain reduction should be evaluated over the course of physic al therapy sessions and moderate to severe proce- dural pain should be treated. Antiepileptic drugs Epilepsy is common among children with I/DD; incidence rates from 14% t o 79% have been reported (Beavis et al., 2007). Th e more severe and extensive the cerebral pathology, the greater is the risk for epilepsy. Diff erent antiepileptic drugs have varyi ng degrees of protein binding and (liver) enzyme induction (Kofk e, 2010). Chronic treatmen t with antiepileptic drugs can aff ect also the pharmacokinetics of other drugs that are me tabolized by the same (P450) enzymatic pathway. Th is could be an explanation for Conclusion Moving forward, the clinical and scientifi c agenda is clear \200\224to con- tin ue to leverage discoveries from basic and clinical pain research and apply them to solve th e problem of pain for children with I/DD. CHAPTER 16 pain in children with intellectual or developmental disabilities 153 Th e remarkable achievements in pain scale development in the last decade for communicative ly and cognitively compromised indi- viduals needs to be converted to demonstrations that p ain is being more eff ectively and effi ciently identifi ed and managed in health- care, re habilitative, educational, and home environments. subjects with I/DD. When possible, evaluations of levels of cogni- tive and communicative f unctioning would be preferable to blanket characterizations (e.g. verbal versus non-verbal) . Better specifi cation of I/DD related features would permit more accurate determination o f how these variables interact with the main phenomena \200\224some aspect of pain \200\224 under investigation. Trials should be developed and designed in accordance with recent cons ensus statements from the IMMPACT group further bringing in line results from studies with children with I/DD with other pediatric pain trials (McGrath et al., 2008). Th e Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT \200\224a recurri ng internationally-recognized consensus group of pain experts from academia, government age ncies, the pharmaceutics industry, and self-help organizations) recommended a number of cor e pain out- come domains including: (1) pain intensity, (2) physical function- ing, and (3) ratings of overall improvement. Th ere is no reason that pediatric pain outcomes research focusing on children with I/DD cannot incorporate the same core outcome domains.