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w w w . e l s e v i e r . c o m / l o c a t e / p a i n

Topical review

Pain in adults with intellectual disabilities

Nanda de Knegt ⇑, Erik ScherderDepartment of Clinical Neuropsychology, VU University, Amsterdam, Netherlands

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

1. Introduction

During the last 2 decades, the number of studies focusing on theexperience, assessment, and treatment of pain in older personswith dementia has increased considerably [30]. One major conclu-sion of those studies [30] is that pain is still undertreated in thispopulation due to the complexity of reliable pain assessment,which is a prerequisite for effective pain treatment. Unfortunately,these pain studies do not address other groups of persons who suf-fer from intellectual disabilities (IDs), such as Down syndrome(DS). The lack of knowledge on the experience, assessment, andtreatment of pain in IDs is more remarkable still for 3 reasons:(1) persons with IDs may suffer from more painful conditions thancontrols do [29]; (2) the prevalence of age-related painful condi-tions is increasing due to increases in estimated life expectancy[5]; and (3) the neuropathology of IDs affects pain-related grayand white matter (Table 1), which may alter pain experience.

The goal of the present topical review is, therefore, to gain moreinsight into the experience of pain in adults with IDs by (1)addressing epidemiological studies on the presence of musculo-skeletal disorders in relation to clinical pain in people with IDs;(2) discussing the available experimental human studies on painin IDs; and (3) presenting theoretical considerations about possiblealterations in pain experience in IDs, based on the neuropathologycharacteristic of the various subtypes.

2. Epidemiological studies on musculoskeletal disorders andclinical pain experience in IDs

The proportion of older adults with IDs who suffer from arthritisand who use analgesics is considerably larger than the comparableproportion of younger adults with IDs [10]. In addition to age, theaetiology of IDs is a factor in the prevalence of musculoskeletaldisorders.

In adults with cerebral palsy, disorders of the hips, back, andlower extremities are common [34] and related to pain experience[32,34]. The pain is caused by arthritis, contractures, spasticity,deformities, and weakness [34]. Female carriers of the fragile-X

0304-3959/$36.00 � 2010 International Association for the Study of Pain. Published bydoi:10.1016/j.pain.2010.11.001

⇑ Corresponding author. Address: Department of Clinical Neuropsychology, VUUniversity, Transitorium Building, Van der Boechorststraat 1, 1081 BT Amsterdam,Netherlands. Tel.: +31 20 598 0708.

E-mail address: nc.de.knegt@psy.vu.nl (N. de Knegt).

mental retardation gene may suffer from neuropathy and chronicmuscle pain, related to fibromyalgia [9]. Scoliosis and excessivelaxity of joints have been observed in fragile-X syndrome [11],but have not been examined in relation to pain experience.

Individuals with DS have a higher risk of musculoskeletal disor-ders than the general population [20,29,33,36]. Instability andother degenerative changes in the cervical spine occur at a muchearlier age in individuals with DS than they do in the general pop-ulation, and these problems increase with age [1]. Arthritis devel-ops in 1% to 2% of adolescents with DS [29], and it occurs moreoften in adults with DS than it does in the general population[33]. Hip instability [20] and osteoporosis, which result in fractures[36], are also common in people with DS. It is worth noting that theextent to which persons with DS suffer from pain from one or moreof these conditions has not been described in literature. Rett syn-drome is characterized by scoliosis, joint deformities, spasticity,and kyphosis [15]. Whether these conditions are related to painexperience remains unknown. The same is true of the 22q11.2Deletion syndrome, the Prader-Willi syndrome, and Williams syn-drome. The 22q11.2 Deletion syndrome is characterized by scolio-sis, patella dislocation, and disk disease [3]; Prader-Willi byscoliosis, osteoporosis, and hip dysplasia [7]; and Williams syn-drome by radioulnar synostosis, kyphosis, lordosis, and scoliosis[28].

Taken together, in most subtypes of IDs, the presence of muscu-loskeletal disorders has not been examined in relation to the expe-rience of clinical pain. Experimental studies on pain in IDs mayprovide more insight.

3. Experimental studies on pain in IDs

In one study, 65% of adults with IDs receiving intramuscularinjections were able to report pain using the Coloured Visual Ana-logue Scale [22]. The frequency and intensity of facial activity didnot differ between subjects who were able to self-report and thosewho were not. This leads to the question of whether adults withIDs experience more or less pain compared to those without IDs.On the one hand, individuals with IDs rate pain experiencesdepicted in photographs of simulated painful situations as moreintense according to a coloured analogue scale compared to peoplewithout IDs [6]. The judgments that people with IDs madeconcerning the location and intensity of pain were not related to

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Table 1The most prevalent subtypes of intellectual disabilities (IDs) and dementia, the prevalence of musculoskeletal disorders, clinical or experimental pain studies, and theneuropathology in pain-related gray and white matter.

Adults withIDs/dementia

Musculoskeletal disorders Clinicalpainstudies

Exp.painstudies

Neuropathology in pain-related gray and white matter

Cerebral palsy Spasticity, scoliosis, arthritis, hip displacement, orthopaedicdeformity, patella alta, cervical stenosis, instability of the cervicalspine, disk degeneration and severe osteoporosis [34].

+

Rett syndrome Scoliosis, joint deformities, spasticity, and kyphosis [15].22q11.2

Deletionsyndrome

Scoliosis, patella dislocation, disk disease [3]. White matter hyperdensities [8].

Downsyndrome

Instability and other degenerative changes in the cervical spine,arthritis [36], hip instability [20].

+ Frontal cortex (including anterior cingulate cortex),amygdala, hippocampus, and locus coeruleus [21,23,28].Decrease of white matter volume in the insula withincreasing age [38]

Fragile-Xsyndrome

Excessive laxity of joints and scoliosis [11]. Frontal lobe, thalamus [26]. Hyperaroused hypothalamic–pituitary-adrenal axis [19]. Reduced white matter inbrainstem (extending into pons), frontal lobe (extendinginto prefrontal cortex), reduced white matter infrontostriatal and parietal sensory-motor tracts [2,16].

Prader-Willisyndrome

Scoliosis, osteoporosis, hip dysplasia [7]. + Insula [27]. Reduced right and left frontal white matter [39].

Williamssyndrome

Radioulnar synostosis, kyphosis, lordosis, and scoliosis [28]. Hippocampus, thalamus. Reduced white matter volume[24].

Alzheimerdisease

+ + Secondary somatosensory cortex, anterior cingulate cortex,amygdala, hippocampus, thalamus, hypothalamus, insula,locus coeruleus, parabrachial nucleus, periaqueductal gray;white-matter lesions [31].

Frontotemporaldementia

+ Middle frontal gyrus, right medial prefrontal cortex,orbitoprefrontal cortex, insula, anterior cingulate cortex,hypothalamus [31].

Vasculardementia

+ Frontal lobe; hyperaroused hypothalamic–pituitary-adrenalaxis. White-matter lesions cortico-subcortical circuits,especially frontosubcortical circuits [31].

+ = one or more clinical and/or experimental (Exp.) pain studies.

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cognitive ability. On the other hand, according to the relatives andrehabilitation staff members of 123 individuals with IDs who wereasked to recall and describe the behaviour of the individual in apain-related situation, 25% of the individuals with IDs had a highthreshold of pain. Moreover, the subjects with more severe IDs weremore likely to show signs of insensitivity or indifference to pain [4].

Experimental studies involving people with DS show that verbalexpressions of pain or discomfort in reaction to an administeredcold stimulus are delayed and that the cold sensation is localized-less precisely on the body compared to a control group. This isexplained by longer pain latencies and difficulties with localisation[17]. When receiving a hot stimulus, individuals with DS giveverbal expressions of pain or discomfort later than members ofthe control group, and at a lower temperature. This is a result ofslower conduction velocities and thus, longer reaction times, anda lower heat-pain threshold [13]. In contrast, a quantitativesensory threshold test showed a significantly higher pain and ther-mal threshold in patients with Prader-Willi syndrome compared tohealthy controls [7].

In conclusion, as far as we know, alterations in the processing ofacute painful and thermal stimuli have been observed only in indi-viduals with DS and Prader-Willi. As clinical and experimentalstudies on pain experience in those with IDs are limited, we willprovide a theoretical consideration of pain experience in the mostprevalent subtypes of IDs, based on the neuropathology that affectspain-related brain regions and white matter in this population.

4. Neuropathology in IDs affects gray and white matter involvedin the processing of pain; theoretical considerations

The intralaminar and medial thalamic nuclei, the insula, theparietal operculum, the hypothalamus, the prefrontal cortex, the

anterior cingulate cortex, the amygdala, and the hippocampusare involved in the motivational-affective aspects of pain, and thecognitive-evaluative aspects of pain. The latter 2 areas are alsoinvolved in the memory of pain, and the hypothalamus in the auto-nomic responses to pain. Sensory-discriminative aspects of painare processed by the lateral thalamus, the primary and secondarysomatosensory cortex, the parietal operculum, and the insula [31].

The neuropathology of the above-mentioned pain-related brainregions (Fig. 1) and white matter (Table 1) may alter pain experi-ence. This appears to be the case in dementia [31], a neurodegener-ative disease that, in contrast to most subtypes of IDs (Table 1), isnot characterized by painful conditions such as musculoskeletaldisorders. For example, in Alzheimer disease, degeneration ofpain-related areas may explain the observed increase in pain toler-ance and hence, the reduction in pain experience. The white-mat-ter lesions (de-afferentiation) that are characteristic of vasculardementia, by contrast, may produce a lowering of pain toleranceand hence, an intensification of the pain experience [31].

This same line of reasoning may be true of those subtypes of IDsthat show neuropathology in pain-related gray matter and whitematter (Table 1). For example, in DS, the degeneration of the hip-pocampus, amygdala, insula, and the anterior cingulate cortex[21,38] may, on the one hand, lead to a decrease in the various as-pects of pain experience, while on the other hand, degeneration ofthe frontal lobe [21] and of white matter [38] may enhance painexperience. The degeneration of the hippocampus, thalamus, andwhite matter volume in Williams syndrome [24] may lead to asimilar hypothesis. In fragile-X syndrome, the degeneration ofwhite matter is a neuropathological hallmark [16] and may causean increase in suffering from pain (lower pain tolerance). The sameline of reasoning may hold for patients with 22q11.2 Deletion syn-drome [37] and patients with Prader-Willi syndrome [27]. Con-

Fig. 1. Pain-related gray matter neuropathology in the most prevalent subtypes ofIntellectual Disability (ID): Down syndrome, fragile-X syndrome, Prader-Willisyndrome, and Williams syndrome. PFC = prefrontal cortex; ACC = anterior cingu-late cortex; Ins = insula; Hypo = hypothalamus; Th = thalamus; Amyg = amygdala;Hippo = hippocampus; LC = locus coeruleus.

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cerning Prader-Willi, our assumption implies that a lower pain tol-erance coincides with the higher pain threshold described earlier[7].

5. Recommendations for pain assessment in IDs

Because clinical pain studies in persons with IDs are limited,recommendations for pain assessment in this population mayemerge from clinical studies on pain in dementia. For a summaryof pain assessment instruments for nonverbal older persons withdementia, see [18]. Most of these instruments include the observa-tion of pain, as expressed in the face or body, for example. Whenusing these scales, one should realize that typical facial expressionsshown spontaneously by some individuals with IDs might be con-fused with facial expressions of pain [12]. Moreover, the level ofthe IDs affects pain behaviour. For example, before the applicationof an acute pain stimulus (vaccination), individuals with severe-profound IDs display a higher level of facial and body expressionsthan individuals with mild-moderate IDs. In the presence of acutepain (during vaccination), assessment of facial pain expression inindividuals with severe-profound IDs becomes less reliable dueto a lack of facial movements (‘‘freezing’’). In contrast, individualswith mild-moderate IDs show an increased level of both facialand body expressions during vaccination [12]. When using visualanalogue pain scales, one should take the visual impairments ofthis population into account [14]. Even limited verbal communica-tion with persons with IDs, such as giving instructions for the useof visual analogue pain scales, requires a special conversation style.Open questions and simple language should be used. To checkwhether the person understands the question, rephrasing thequestion by changing the sequence of words should lead to thesame answer. The reason for this is that persons with IDs tend toanswer ‘‘yes’’ to every closed question and to repeat the finaloption in questions with multiple answers [35].

6. Conclusions

� In most subtypes of IDs, the presence of musculoskeletal disor-ders has not been examined in relation to the experience of clin-

ical pain. In other words, clinical pain studies with persons withIDs are lacking. This is remarkable, because adults without IDsrate chronic musculoskeletal disorders such as arthritis assevere or extremely painful [25].� As far as we know, alterations in the processing of acute painful

and thermal stimuli have been examined only in experimentalstudies including individuals with DS and Prader-Willi syn-drome. Individuals with DS react relatively slowly whenexpressing a verbal response to cold and hot stimuli, have diffi-culty localizing cold stimuli, and experience heat as painful at alower temperature. These findings are quite alarming, as theycould implicate that a person could experience intense painfrom a hot object while being less able to express a verbalresponse quickly enough to avoid burns.� The neuropathology in pain-related brain regions and white

matter suggests that in DS and Williams syndrome, pain expe-rience may either decrease or increase. Patients with the frag-ile-X syndrome, the 22q11.2 Deletion syndrome, and thePrader-Willi syndrome may suffer from an increase in painexperience. Clinical studies are needed to confirm or rejectthese hypotheses.� Because the hippocampus, anterior cingulate cortex, prefrontal

cortex, and other brain areas of the medial and lateral pain sys-tem are also involved in cognitive functioning, future studiesshould address the question of whether any positive or negativerelationship actually exists in IDs between cognitive function-ing and various aspects of pain, such as the motivational/affec-tive aspects of pain. If there is such a relationship, irrespectiveof its nature, neuropsychological examination might contributeto pain assessment in this population.

Conflict of interest

There are no conflicts of interest to report.

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