Hindawi Publishing Corporation
The Scientific World Journal
Volume 2013, Article ID 916178, 20 pages
Pain Sensitivity and Observer Perception of Pain in
Individuals with Autistic Spectrum Disorder
C. S. Allely
Institute of Health and Wellbeing, University of Glasgow, RHSC Yorkhill, Glasgow G3 8SJ, UK
Correspondence should be addressed to C. S. Allely; email@example.com
Received 17 April 2013; Accepted 30 April 2013
Academic Editors: C. Gillberg and H. Minnis
Copyright © 2013 C. S. Allely. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The peer-reviewed literature investigating the relationship between pain expression and perception of pain in individuals with
ASD is sparse. The aim of the present systematic PRIMSA review was twofold: first, to see what evidence there is for the widely
held belief that individuals with ASD are insensitive to pain or have a high pain threshold in the peer-reviewed literature and,
second, to examine whether individuals with ASD react or express pain differently. Fifteen studies investigating pain in individuals
with ASD were identified. The case studies all reported pain insensitivity in individuals with ASD. However, the majority of the
ten experimental studies reviewed indicate that the idea that individuals with ASD are pain insensitive needs to be challenged. The
findings also highlight the strong possibility that not all children with ASD express their physical discomfort in the same way as a
neurotypical child would (i.e., cry, moan, seek comfort, etc.) which may lead caregivers and the medical profession to interpret this
as pain insensitivity or incorrectly lead them to believe that the child is in no pain. These results have important implications for
the assessment and management of pain in children with ASD.
Autistic Spectrum Disorder (ASD) describes a range of
conditions classified as pervasive developmental disorders
(PDDs) in the Diagnostic and Statistical Manual of Mental
pervasive developmental disorder not otherwise specified
drome. However, typically only the first three are considered
part of the autism spectrum . ASDs have an onset in early
childhood and adverse, often lifelong, effects on communi-
cation, socialisation including tendencies toward restricted
interests and/or repetitive behaviours . Often associated
with these symptoms are sensory-perceptual anomalies
which occur in approximately 70% of cases . To determine
the prevalence of autism and related disorders, the Centers
for Disease Control (CDC) conducted a study examining
8-year-old children living in 14 sites in the United States
and found that 1 in 150 children are living with an ASD .
genesis of ASD, the causes remain uncertain .
ities related to sight, hearing, touch, smell, and/or taste that
include an increased sensitivity to pain. The processing of
these types of incoming information might be distorted; rain
might sound like gunfire, clothing might feel like sandpaper,
or fingers shampooing a scalp might feel like sharp metal
. Such unusual responsiveness to the environment has
been suggested to be partly due to stimulus overselectivity,
the tendency of individuals with ASD to respond only to
a very limited amount of the relevant sensory information
the same individual [3, 8–10]. Stereotyped and self-injurious
behaviours (SIBs) are also exhibited in significant numbers
of individuals with ASD [11–15] which has been associated
patients may show self-injurious behaviour at some point in
in relation to self-injury is unclear [18–22].
2 The Scientific World Journal
Numerous biochemical theories have been put forward
to explain the apparent pain insensitivities in individuals
with ASD. Certain repetitious activities such as rocking, arm
flapping, or pacing produce an increase (or build up) of the
level of released endorphins which can lead to a reduction of
the sensation of pain, which may explain why children with
an ASD who have physical accidents report feeling less pain
when the accidents take place later in the day . A number
of researchers have also suggested that excessive brain opioid
activity could explain the apparent pain insensitivity of ASD
[24–30]. The opioid hypothesis for ASD postulates that this
“hyperfunction of the endogenous opioid system” may actu-
ally explain some, if not all, of the symptoms associated with
ASD including (1) reduced socialisation (and aloofness), (2)
itive stereotyped behaviours, (5) promotion of convulsive
ful stimuli, or the expression of pain, in infants, children or
adults with ASD has been conducted. Accurate pain assess-
ment, in order to provide appropriate and timely care, can
be a challenging task especially in children with ASD .
However, pain assessment strategies for children with ASD
the relationship between pain and ASD in the pain literature
is a greater likelihood that their pain may go unrecognised
and untreated (e.g., [34, 35]). Another potential barrier to
assessing pain in children with ASD is the prevailing belief,
sion, that pain insensitivity is a common feature in children
with ASD (e.g., [2, 36–40]). Parents, caregivers, and mental
health professionals have reported that some children with
ASD appear to withstand painful stimuli (bumps, cuts, etc.)
show absence of nociceptive reflexes (e.g., absence of hand
body position in cases of broken legs or arms . However,
nearly all of the support for this notion of pain insensi-
tivity is derived from anecdotal reports and limited clinical
observations [24–29, 42–44]. Despite the lack of systematic
studies of pain sensitivity and reactivity in ASD, the pres-
ence of pain insensitivity in ASD has been given further
validation because of its inclusion as an associated feature
in standard diagnostic texts. In DSM-IV and DSM-IV-TR “a
high threshold for pain” is described [2, 45] while in DSM-
III the “ignoring of pain” is described (APA, 1987). Not only
are children with ASD considered to have “reduced pain sen-
sitivity,” but they have also been described as “not feeling
pain as intensely as others” , having an “indifference
to pain”  and having a “high threshold for pain” .
The belief that children with ASD are insensitive to pain
may bias observers’ judgements of pain in these children
It is important to understand the behaviours observers
can use to assess pain in children and adults with ASD and to
understand the potential bias of pain sensitivity information
on observers’ judgements of pain. Over the last decade there
has been a plethora of studies investigating pain expression
and perception in individuals with intellectual disabilities or
individuals with developmental disabilities (often the exact
diagnostic nature of these groups is not specified) (i.e., [47–
50]). By contrast, peer-reviewed literature investigating the
relationship between pain expression and perception of pain
in individuals with ASD is sparse. Research on pain in chil-
dren with developmental disabilities has almost exclusively
relied on observational or behavioural assessment measures
[51, 52]. The present systematic review was carried out using
PRISMA guidelines  to primarily identify and examine
the evidence for the widely held belief that individuals with
ASD are insensitive to pain or have a high pain threshold.
Additionally, this review will examine whether individuals
with ASD react or express pain differently.
Internet-based bibliographic databases (PsycINFO and
PubMed) were searched to access studies which examined
orbidity in their sample). Studies which investigated pain in
individuals with ASD who also had another disorder, such
as mental retardation, were not included because the present
review was specifically interested in the impact pure ASD
has on pain sensitivity and expression of pain. Studies which
investigated pain in individuals with ASD on a psycho-
logical/behavioural level were included. Numerous studies
were excluded as they explored more medical issues related
mation and alterations in intestinal microflora).
It is commonly reported in the literature that sensory
disturbances can feel painful to individuals with ASD. For
instance, rain might sound like gunfire and the individual
finds this so painful that they have to cover their ears.
riences were not included as the present review is interested
in what is considered to be well-known painful events to the
majority of individuals, such as needles in the skin and high
papers can be seen in the flowchart (following PRISMA
guidelines, ) (Please see Figure 1 for the Flowchart).
Duplicates were excluded prior to the retrieval of references.
Searches on the two databases were originally conducted
on October, 18, 2012 and updated on February, 6, 2013. The
following search criteria were entered into PubMed: [“pain”
entered into PsycINFO: [“pain” (all text) AND “autis∗”]
of 274 abstracts. In addition to these database searches, num-
erous permutations of ASD and pain were entered into
Google Scholar and thoroughly searched for any additional
articles not found in the database searches. For instance,
[Asperger AND pain]; [autism AND pain]; [ASD and pain].
an abstract of a pilot study (the findings of which have not
which returned a total of 148 references. Combining the
abstracts returned on these two databases, there was a total
a total of 126 references. The following search criteria were
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Number of references
Number of duplicates
removed through reading
titles of abstracts—12
Number of additional
through other sources—1
Number of abstracts
Number of full text
articles assessed for
Number of full text articles excluded—
28. (11 investigated samples which
were not individuals with ASD but
individuals with intellectual
disabilities or developmental disorders—
which were often not detailed; 3
were on studies with individuals with
mental retardation and ASD, and 14
were found not to be relevant).
Number of papers
Number of papers
Number of studies
included in the
(note—one of these was
an abstract of the
findings from a pilot
Number of references
14 (non-English language
Figure 1: Flow of information through Systematic Review.
Abstracts for each reference were obtained and screened
using the following criteria.
(1) Human study population.
in individuals with ASD.
(1) Paper not published in English.
(3) Book reviews.
4 The Scientific World Journal
(4) Studies which investigated a sample that comprised
of individuals with a disorder other than ASD (for
instance, developmental disabilities or intellectual
mental retardation) were excluded.
Screening. In the first stage, papers were rejected which
(i) investigated medical issues (such as intestinal inflam-
mation) or clinical psychopharmacology aspects of
(ii) were not published in the English language.
For the next stage, papers were rejected which were not
studies that involved a sample of individuals with ASD.
In addition, review papers and book chapters which were
clearly reviews were excluded. Full documents were obtained
for the remaining records.
Five case studies and ten experimental studies were found in
the PRISMA search that investigated some aspect of pain in
individuals with ASD.
3.1. Case Studies. Table 1 details the five case report studies
which explored pain perception, expression, or observer
perception of pain in individuals with ASD.
Pain experts might be underrecognising signs and symp-
toms of ASD in their patients, a notion which led Bursch et
al.  to explore this in two patients (Tony and Gregg) who
displayed signs and symptoms indicative of possible ASD.
Tony’s mother reported a possible sensory disturbance in
early childhood in that he liked to belt his trousers extremely
tightly, which most children would have found painful, but
Tony liked the sensation. His mother reported that he once
grabbed a hot frying pan and did not seem to respond in
a way typical of someone in pain. Despite both adolescents
showing obvious signs and symptoms indicative of an ASD,
review of previous medical records and parental interviews
suggested that health care professionals did not identify the
need for evaluation of these unusual characteristics. This is
clinically useful to recognise because any type of pain might
be exacerbated by sensory processing abnormalities and/or
persistent arousal that often characterise patients with ASD
Elwin et al. reviewed 17 works published in English
or Swedish and 10 autobiographies to explore hyper- and
hyposensitivity in individuals with ASD in the context of
verbal expression. The autobiographies were written by indi-
viduals who all had an ASD diagnosis. The authors found
much evidence to suggest pain insensitivity (hyposensitivity)
in individuals with ASD in that pain could be indistinctly
experienced. Several authors indicated that they had a very
high pain threshold. For instance, one individual reported
“Injuries could easily go undetected. In there, I was given a
punch in the stomach, every day, though usually only one.
Perhaps I was not much fun to hit because I had a very high
pain threshold, and even when I did hurt I never showed
what I felt. I did not know that was what you should do”
[57, page 92]. They also found evidence of pain sensitivity
(hypersensitivity). However, for the purposes of the present
review we have excluded this as from the descriptions given
in the paper by Elwin et al. , this was pain which
was experienced as a result of sensory abonormalities not
specifically related to what would typically be defined as a
painful event (such as bodily injury or needle injection).
They reported cases where the individual reported feeling
excruciating pain racking through her head in response to a
Rutherford  described the development of an infant
(N.F.) who was later diagnosed with ASD in direct com-
parison to the development of his twin, from the prenatal
period to the age of four years, through the examination of
personal journals and medical records kept by the mother
of the twins. Several differences in development between the
twins, some as early as six months of age, were found and
of particular interest was the observation that N.F. frequently
showed insensitivity to pain which was exhibited as early as
six months of age. Differences reemerged by the age of four
years, at which point N.F. would wake up frequently during
the night, sometimes as many as nine times. He would cry
and yell during these times and his mother thought that he
appeared to be in extreme pain.
Autoextraction of teeth (self-extraction of a tooth) is
an unusual form of self-injurious behaviour (SIB) and is
rarely seen in children with ASD.Ross-Russell and Sloan 
present the case of a seven-year-old boy with mild ASD who
experienced unexplained dental pain and subsequently went
on to extract his own lower right deciduous canine tooth. He
has also demonstrated SIB in the form of head banging. He
was brought to the clinic complaining of pain of about one
week’s duration that was increasing in intensity, was present
most of the time, and was not sensitive to hot, cold, or sweet
stimulus. Within 24 hours the patient was again back at the
clinic as the pain had not resolved with ibuprofen and by
this time his lower right deciduous canine was very slightly
mobile. The tooth had normal root anatomy and no evidence
of alveolar bone loss was evident but by the next day the
patient had extracted his lower right deciduous canine tooth,
which was witnessed by his mother. He claimed it had been
“itching” him until he got it out. This case indicates that the
patient was insensitive to pain to some degree.
apist in an interprofessional (IP) school-based clinic worked
together to meet the needs of a nine-year-old child with
pervasive developmental disorder, not otherwise specified,
with atypical classroom behaviours and declining student
performance. The child denied pain of any type, using a 0-
to 10-point visual analogue scale. The IP team noted that the
student was speaking less to other students, faculty, and staff.
Although such behaviour could be a sign of withdrawal, it
may also be a sign of oral problems. As five weeks had passed
without any change in the student’s demeanor, the child was
two teeth. The dentist reported that an abscess of this size
without pain is unusual, given the size, the depth, and the
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Table 1: Case report studies which explored pain perception, expression, or observer perception of pain in individuals with ASD.
Level of functioning
of ASD sample
Aim of the studyFindings
Bursch et al. 
2 patients with the
signs and symptoms
Does not specify.
Case report of 2 patients
and their sensory
abnormalities and pain
perception as observed by
To explore hyper- and
individuals with ASD in the
context of verbal
expression. Using samples
autobiographies as a data
To describe how a nurse
and a physical therapist in
an interprofessional (IP)
collaborated to meet the
needs of a child with
PDD-NOS, with atypical
classroom behaviours and
Reported evidence of lack of pain
sensitivity in both patients. That is,
“...once grabbed a hot frying pan and did
not seem to respond in a way typical of
someone in pain.”
Elwin et al. 
17 works published
in English or
Swedish and 10
Does not specify for
Yes, self-reported pain insensitivity.
Pain could be indistinctly experienced,
and several authors pointed out having a
very high pain threshold. Injuries could
easily go undetected.
Mieres et al. 
9 year old with
Does not specify.
Yes: parental report of pain insensitivity.
For this student, pain was an unreliable
indicator of both a dental infection and
piercing of skin by thorny objects.
Child was referred to a dentist who
discovered a severe abscess affecting two
teeth. The dentist reported that an abscess
of this size without pain is unusual, given
the size, the depth, and the proximity to
Yes, suggestion that this patient had pain
and Sloan 
7-year-old boy.Mild ASD.
Report of a case of a young
child with mild ASD who
presented with unexplained
dental pain and who
subsequently went on to
extract his own lower right
deciduous canine tooth.
“He has also demonstrated SIB in the
form of head banging. He was brought to
the clinic complaining of pain of about
one week’s duration that was increasing in
intensity which was present most of the
time and was not sensitive to hot, cold or
sweet stimulus. Within 24 hours the
patient was again back at the clinic, as the
pain had not resolved with ibuprofen, and
by this time his lower right deciduous
canine was very slightly mobile. No
evidence of alveolar bone loss and the
tooth had normal root anatomy. By the
next day the patient had extracted his
lower right deciduous canine tooth,
witnessed by his mother. He claimed it
had been ‘itching’ him until he got it out.”
Twins: boy who was
diagnosed with ASD
at 3 years and 1
month, and a girl
Does not specify.
Describes the development
of an infant who was later
diagnosed with ASD.
Directly compares his
development to that of his
twin from a prenatal period
through to the age of 4
years. Explored through
examination of personal
journals and medical
records kept by the mother.
Yes: evidence of pain
N.F. frequently showed insensitivity to
pain which was exhibited as early as 6 to
12 months of age.
6 The Scientific World Journal
proximity to bone. The abscess required two 10-day rounds
of antibiotics until the infection was completely remedied.
Two months later, the same student arrived in the clinic and
stated that he was “not able to concentrate and the noise was
bothering him.” Again, the student denied pain, using a 0- to
same scale of 0 to 10 and instead asked, “How uncomfortable
are you?” the student stated about a 7. Multiple superficial
cuts and lacerations, some covered with bandaids, were seen
bilaterally. When the mother was called from the clinic,
she stated that over the weekend the student played in the
sand dunes without shoes. She further stated that the other
children playing with him left quickly after complaints of
not understand why the other children were complaining.
Later, the mother discovered bleeding cuts on his feet and he
was taken to a 24-hour clinic, where the physician removed
14 sand spurs. The student helped in the removal of the sand
deep. However, the following morning, he complained of
excessive noise, did not wish to be touched, and covered his
head. The student stated at first that he had a 0 in a pain scale
of 0 to 10. However, when asked, “How uncomfortable are
you?” the student indicated a 7. For this student, pain was an
skin by thorny objects, preventing timely treatment.
In sum, the five reported case studies all seem to provide
some support to the widely held belief that individuals with
ASD are insensitive to pain or have a high pain threshold.
3.2. Experimental Studies. Table 2 details the experimen-
tal studies which explored pain perception, expression, or
observer perception of pain in individuals with ASD. There
were ten experimental studies identified in the search of
study. The ten studies are split up into five different sections
under the subheadings of “Facial Activity to Pain Stimuli in
ASD” (no. 3); “Pain Sensitivity Experienced in ASD” (no.
4); “Embodied Pain in ASD” (no. 1); “Relationship between
Opioid Hormone and ASD” (no. 1) and “Oversensitivity to
Pain and Age of Diagnosis of ASD” (no. 1).
3.3. Facial Activity to Pain Stimuli in ASD. Facial activity has
been found to be a major determinant of observers’ judge-
ments of pain in infants , children , and adults with
cognitive impairments . The widely held belief that chil-
dren with ASD are less sensitive to pain compared to neuro-
typical children may bias observers’ interpretation of pain
expression/behavioural reactivity in these children. Messmer
et al.  investigated whether the perceptions of pain in
children with ASD could potentially be influenced by the
belief thatchildren withASDare insensitiveto pain.Twenty-
seven undergraduate psychology students who had no previ-
ous experience with children with ASD were recruited at the
University of British Columbia. The sample consisted of 23
females and four males, with a mean age of 20.11 years. Nine-
teen of the participants identified themselves as Caucasian,
seven participants identified themselves as Asian, and one
identified him/herself as “other.” Observers received infor-
mation that pain experience in children with ASD is either
the same as, more intense than, or less intense than child-
ren without ASD. After viewing six video clips (which were
below) of children with ASD undergoing venepuncture,
observers estimated pain intensity using a visual analogue
scale. Venepuncture is a medical procedure which requires
the use of a needle to puncture a patient’s vein. Puncturing
a vein provides direct access that allows for extraction of
venous blood or insertion of medication or fluids directly
into the blood stream and is the same basic procedure which
is used to extract blood for blood donations. The sample of
children with ASD used for the current study consisted of
four boys and two girls between the age of three and seven.
The clips consisted of the 10 seconds immediately preced-
ing the injection and the 10 seconds immediately after needle
insertion. Participants were randomly assigned to one of the
three groups. Group A consisted of seven participants, and
groups B and C consisted of 10 participants. Each group
ren with Autism: A Parent’s Guide Describing Features of
Autism” . Within the general account was a description
of pain in individuals with ASD was different for each group,
saying either (a) “Children with autism appear to respond to
pain in the same way that children without autism do”; (b)
“Children with autism also appear to respond to pain differ-
ently than children without autism. In particular, they feel
pain more than other children. This has been termed “pain
hypersensitivity” and has recently been documented in
research on children with autism”; or (c) “Children with
autism also appear to respond to pain differently than child-
ren without autism. In particular, they seem to have a high
tolerance for pain and do not appear to feel pain as much as
After reading the booklet, participants watched six video
clips of children with ASD undergoing venepuncture. The
the Child Facial Coding System (Child Facial Action Coding
System Revised Manual, CFCS ). The CFCS is a facial
coding system which was created as a way to assess pain
experiences in children. Thirteen explicitly defined facial
actions (e.g., brow lower, eye squeeze, and nose wrinkle) are
ment.After each video clip,participantsratedthepaininten-
sity of the child on a visual analogue scale (VAS), a 100mm
horizontal line anchored on the left by “no pain” and on the
right by “worst possible pain.” Participants placed a mark on
the line to indicate how much pain they thought the child
was feeling. The VAS is a valid measure for assessing pain
intensity . Mean pain intensity scores on the VAS were
compared to the average facial pain activity scores from the
CFCS. A Spearman rank order correlation suggested that the
order of VAS ratings was highly correlated with the order
of the CFCS scores (푟푠 = 0.943, 푃 < 0.01). In sum, the
main findings of this study by Messmer et al.  were that
children who received lower scoreson the CFCSwere judged
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Table 2: Experimental studies which explored pain perception, expression, or caregiver/observer perception of pain in individuals with ASD.
Level of functioning of
Aim of the study
20 ASD (17 boys; 3 girls) & 20 TD
controls (16 boys; 4 girls). Age
range: 8–18 years.
Assessing self-report of pain using vignettes
and also comparing this to parental reports.
No significant differences in pain intensity ratings between
the ASD and controls.
No significant differences between the pain ratings of
youths with ASD or their parents as compared with a
sample of typically developing youths.
Cascio et al.
8 adults with ASD (clinical
diagnoses of either Autistic or
Asperger Disorder; all had IQ of
at least 70 (7 males & 1 female
(mean age 29.3 years, range
20–45). 8 adults without ASD
(sex and age matched). (mean
age 29.0, range 21–45).
To investigate tactile sensitivity in adults with
autism using a variety of stimuli, in order to
probe different submodalities of
Experiment specifically related to present
review—thermal pain threshold.
Yes, significant difference—ASD group showed a greater
degree of pain sensitivity.
For cold pain, there was a main effect of site (퐹 = 5.12,
푃 = 0.0250), and group (퐹 = 3.84, 푃 = 0.0518), with the
ASD group displaying average cold pain thresholds of
16.68∘C, compared to the control group average of 9.04∘C.
For heat pain, there was a significant effect of group. The
average threshold for the ASD group was 43.66∘C, while
that of the control group was 46.58∘C.
5 children with a documented
ASD (between the age 7–11
Does not specify.
A pilot study to investigate pain and distress in
children with autism during a dental cleaning
Children with ASD exhibited greater pain scores (M
= 29.8) than children without ASD (M = 10.0). Greater
levels of interfering distress behaviour were exhibited in
the children with ASD. Moderate associations between
severity of ASD symptoms and pain during the dental
cleaning procedure (푟 = .55) and interfering distress
behaviours (푟 = .43), with increased severity of the child’s
symptoms relating to higher levels of pain and distress.
Population-based group of 208
diagnosed with ASD and referred
to a specialised habilitation
centre for early intervention.
Children were sub-grouped (8 in
total) based upon degree of ASD
symptoms & cognitive level.
Subgroups (i.e., classic
autism, nuclear autism)—but does not
specify low or high
To describe sensory abnormalities in
preschool children with an ASD, compared to
different subgroups within the autism
spectrum in terms of the presence of sensory
abnormalities, and relate the findings to other
clinically relevant symptom domains.
Yes: significant differences in pain sensitivity.
Under-reactivity to pain in 40% of the sample.Under-reactivity to cold and heat were reported for 22%
and 7%, respectively.
Children with self-injurious behaviours had more sensory
abnormalities affected (M = 2.0, SD = 1.5, 푛 = 61) than
children with no such behaviours (M = 1.3, SD = 1.2,
푛 = 147); 푡(206) = 2.791, 푃 = 0.006.
Mandell et al.
Survey data were collected in
Pennsylvania from 969
caregivers of children who had
ASD and were younger than 21
years regarding their service
Does not specify low or
high functioning in
terms of DSM and so
Early diagnosis of children with ASD is critical
but often delayed until school age. This study
attempted to identify these factors among a
community sample of children with ASD.
Oversensitivity to pain was associated with a 0.6-year
increase in the age of diagnosis.
8 The Scientific World Journal
Table 2: Continued.
Level of functioning of
Aim of the study
6 ASD individuals (4 boys and 2
girls between 3 and 7 years).
Video clips of children
with ASD undergoing
obtained from a
previous study ; see
below for details.
To examine the influence of information about
the pain experience of children with autism on
observers’ judgement of pain intensity in
children with ASD and to examine the impact
of facial activity on observers’ judgement of
pain intensity in children with ASD.
Facial activity had a significant impact on observers’
estimates of pain intensity while pain sensitivity
information did not.
Paluello et al.
16 right-handed men with ASD
(aged 28.0 ± 7.2 years) and 20
neurotypical controls (aged 25.3
± 6.7 years) age, sex, and IQ
Mention levels of
severity in terms of score
on the AQ.
To explore whether people with AS differ from
neurotypical control participants in
their empathic corticospinal response to the
observation of others’ pain and the modulatory
role played by phenomenal experience of
observed pain and personality traits.
Participants with AS, compared with control participants,
tended to judge the touch as more painful (푡 = −1.82,
Nader et al.
21 3-year-old to 7-year-old
children with ASD and 22
Mean CARS score for
the ASD group was 39.10
(SD = 4.98, range
30.5–47), which put the
average for the group
into the severely autistic
range (CARS score >37).
9 fell into the
range (CARS score
30–37), and 12 fell into
the severely ASD range.
Aims of the study were to (1) characterise the
behavioural response of children with ASD
experiencing a venepuncture using objective
observational measures of pain and distress,
(2) examine parents’ assessments of pain
behaviour in children with and without
autism, including comparison of the
relationship of parental reports with
behavioural measures, and (3) compare thebehavioural reactions and parental
assessments of children with ASD with
children without ASD undergoing
In contrast with many of the other studies reported in this
review, this study found evidence which indicates that
individuals with ASD do not have an insensitivity to pain
as manifested by a lack of behavioural response—children
with ASD display a significant behavioural reaction in
response to a painful stimulus.
Using FPS scores as a measure of parental assessment of
pain response following the venepuncture, parents of
children with ASD reported observing more pain in theirchildren during the venepuncture (M = 4.29, SD = 1.45)
compared with parents of the children without autism (M
= 2.75, SD = 1.90; 푡(41) = 2.97, 푃 < 0.05). Using the
NCCPC as a retrospective measure of parental assessment
of typical pain reactivity in their children, scores did not
differ between the autism group (M = 60.33, SD = 13.50)
and comparison group (M = 58.41, SD = 14.19; 푡(41) =
0.46, 푃 > 0.05).
Parent reports of pain temperament in children with ASD
(M = 2.72, SD = 1.32) were similar to parent reports of
pain temperament in the children without ASD (M = 2.82,
SD = 1.30; 푡(38) = −0.23, 푃 > 0.05).
19 Japanese children (17 boys, 2
girls, mean age 4.23 ± 1.18 years,
range 2.00–6.42) with typical
infantile autism. 23
controls—age-matched Japanese children (18 boys, 5 girls, mean
age 3.78 ± 3.37 years, range
0–10.75). 3 patients with Rett
syndrome (3 girls, ages 10–14
Does not specify.
To clarify whether P-endorphin plays an
important role in infantile autism, we
determined the cerebrospinal fluid (CSF) levels
of p-endorphin and evaluated the correlation
between these levels and ASD symptoms.
Finding do not support the opioid hypothesis to explain
pain sensitivity in ASD.
No significant correlation between CSF levels and clinical
symptoms, including self-injurious behaviour, pain
insensitivity, and stereotyped movement. However, CSF
levels of p-endorphin were significantly higher in the
patients with Rett syndrome than in the control (푃 < 0.05).
Data suggest that neurons containing p-endorphin may
not be involved in patients with infantile autism.
The Scientific World Journal9
Table 2: Continued.
Level of functioning of
Aim of the study
73 children and adolescents with
ASD and 115 control matched for
age, sex and pubertal stage. (ASD
group 49 males and 24 females.
ASD group total age 11.7 plus or
minus 4.5; comparison group 75 males and 40 females. Total age
12.7 + or −5.9).
Individuals with “severe”
ASD (푛 = 39).
Individuals with “mild”
to “moderate” ASD
(푛 = 39). Normal
controls (푛 = 103).
To examine behavioural and physiological
pain responses, plasma b-endorphin levels,
and their relationship in a large group of
individuals with ASD.
No: individuals with ASD do not have decreased
sensitivity to pain.
A high proportion of individuals with ASD displayed
absent or reduced behavioural pain reactivity at home
(68.6%), at day care (34.2%), and during venepuncture (55.6%). Despite their high rate of absent behavioural pain
reactivity during venepuncture (41.3 versus 8.7% of
controls, 푃 < 0.0001), individuals with ASD displayed a
significantly increased heart rate in response to
venepuncture (푃 < 0.05) which was significantly greater
than for controls (mean 6 SEM; 6.462.5 versus
1.360.8beats/min, 푃 < 0.05). Plasma b-endorphin levels
were higher in the ASD group (푃 < 0.001) and were
positively associated with ASD severity (푃 < 0.001) and
heart rate before or after venepuncture (푃 < 0.05), but not
with behavioural pain reactivity.
AQ: Autism Spectrum Quotient .
CARS: The Childhood Autism Rating Scale .CFS: Cerebralspinal fluid.CNS: Central Nervous System.
PDD-NOS: Pervasive Developmental Disorder Not-Otherwise Specified.
TD: Typically developing.
10The Scientific World Journal
to be experiencing a lower intensity of pain and children
who received higher scores on the CFCS were judged to be
experiencing a higher intensity of pain. Thus, Messmer et al.
 found that observers’ ratings of pain in children with
ASD were not influenced by information regarding the pain
experience in children with ASD and that they were able to
use facial activity as one basis for estimating pain in child-
ren with ASD. This study also indicates that the children’s
experience of pain is communicated, at least to some degree,
through their facial activity.
Nader et al.  conducted a study in order to exam-
ine the behavioural response of children with ASD during
venepuncture using an objective observational measure of
pain and distress. In addition to this objective measure, they
also examined parents’ assessments of pain behaviour in
children with and without ASD, including comparison of the
relationship of parental reports with behavioural measures.
All of these measures were compared to the same assess-
ment conducted on control children during the same pro-
cedure. Nader et al.  recorded behavioural distress and
Parents provided observer reports of pain and facial activity
was used as an objective behavioural measure of pain.
Detailed coding of videotapes were performed using the
Child Facial Coding System  (which was the objective
measure also used in the study above by Messmer et al. ).
An objective measure of distress was also used in the present
study, namely, the Observational Scale of Behavioral Distress
behavioural distress in children undergoing painful medical
procedures. OSBD consists of eight operationally defined
behaviours indicative of anxiety and/or pain behaviour in
Observer reports of pain from the parents were mea-
sured using the following two procedures. Histories of pain
sensitivity were assessed by asking the parents to report on
prior pain reactions of their children using the Non-Com-
were also asked to provide a summary report of their child’s
pain temperament by responding to the following statement:
“My child is very sensitive to pain of bumps or cuts or other
common hurts.” The parent responded to this question on
a scale of 1 = not typical/characteristic to 5 = very typi-
cal/characteristic. Lastly, the Faces Pain Scale (FPS; ) was
given to the parents. This consists of seven faces showing
to pain). The parents were asked to select the face that they
felt represents the degree of pain experienced by their child
during the venepuncture procedure.
Findings from the study by Nadar et al.  revealed
overall similar to the comparison group, except the substan-
tial facial pain reactivity instigated by the venepuncture in
the children with ASD exceeded that found in the control
group. The degree of concordance between parental report
and observed pain responses were consistently better for the
comparison group. For the ASD group, no significant cor-
relation was observed between the FPS scores provided by
the parents and the facial pain responses of the children,
푟 = −0.154, 푃 > 0.05. Interestingly, children with ASD who
tions and behavioural distress in response to the venepunc-
ture. Using FPS scores as a measure of parental assessment of
pain response following the venepuncture, parents of child-
1.90; 푡(41) = 2.97, 푃 < 0.05). Using the NCCPC as a retro-
reports of pain temperament in children with ASD (푀 =
had been assessed by their parents as having a lower pain
sensitivity and reactivity tended to show greater facial reac-
during the venepuncture (푀 = 4.29, SD = 1.45) compared
spective measure of parental assessment of typical pain
reactivity in their children, scores did not differ between the
with parents of the children without ASD (푀 = 2.75, SD =
(푀 = 58.41, SD = 14.19; 푡(41) = 0.46, 푃 > 0.05). Parent
ASD group (푀 = 60.33, SD = 13.50) and comparison group
푡(38) = −0.23, 푃 > 0.05). In addition, although the ASD
demonstrate that children with ASD can display a signifi-
cant behavioural reaction in response to a painful stimulus
which is in contrast to the widely held belief in the literature
that individuals with ASD are insensitive to pain. However,
pret their child’s pain expression accurately. Children with
ASD, who had been assessed by their parents as having a
lower pain sensitivity and reactivity, tended to show greater
facial reactions and behavioural distress in response to the
venepuncture. However, this is difficult to draw strong con-
clusions from this since it may be that the event was simply
they had any greater degree of pain sensitivity.
In another study, Tordjman et al.  examined behav-
ioural and physiological pain responses, plasma beta-endo-
rphin levels and their relationship in 73 children and adoles-
sex, and pubertal stage during blood drawing. Pain reactivity
was assessed for patients in three different observational
preceding the blood drawing; (2) at home, where parents
rated pain-related behaviour during the same month as the
tions involving pain to distinguish reactions to a variety of
types of noxious and painful stimuli such as being burned,
having internal pain (tooth pain, ear infection, headache,
etc.), and other accidental painful stimuli (cutting, pinching,
banging, etc.); (3) during the blood drawing at a medical
centre, when a direct clinical observation was conducted by
a nurse and child psychiatrist not belonging to the caregiver
team. Normal controls were similarly assessed for pain reac-
Pain Reactivity Scale (PL-BPRS) . The scale looks at five
different pain scenarios, namely, (1) paradoxical pain reac-
tivity, the apparent pleasure reaction to a painful stimulus
(such as smiling or laughing); (2) absence of pain reactivity,
severity of the ASD group was well characterised and ranged
from mild to severe, there was no information about level of
ament in the children without ASD (푀 = 2.82, SD = 1.30;
The Scientific World Journal11
drawal reflex when burning oneself or absence of arm with-
drawal reflex from the needle during a blood drawing); (3)
hyporeactivity to pain, incomplete pain reactivity or abnor-
mally delayed reaction time to painful stimulus; (4) nor-
mal pain reactivity such as cries, screams, moaning, gri-
maces, reflexes of nociceptive withdrawal, lack of movement,
body orientation, and glance towards the painful area, and
lastly, (5) hyperreactivity to pain, disproportionate cries, and
screams given the painful stimulus (with hypersensitive light
touch). A checklist was used to indicate the presence or
stereotyped behaviours, and social withdrawal during the
blood drawing situation. Physiological measures included
plasma b-endorphin levels analysis and a heart rate measure-
ment to examine cardiovascular response to the blood draw-
ing (with a stethoscope placed on the thorax considering
that some patients can react negatively when their wrist is
touched) immediately before and after the venepuncture (15-
second measurement period).
Tordjman et al.  found that across the three observa-
tional situations, abnormal behavioural responses to painful
stimuli were highly prevalent in individuals with ASD of low
reactive or absent pain reactions in the ASD group. A high
proportion of individuals with ASD displayed absent or
reduced behavioural pain reactivity at home (68.6%), at day
care (34.2%) and during venepuncture (55.6%). Although
this pattern of observed behaviour is consistent with a num-
ber of previous studies, most prior reports did not distin-
guish pain reactivity from pain sensitivity. It is critical to
keep this distinction in mind and not to conclude that
absence of behavioural pain reactivity means absence of pain
sensitivity. Despite their high rate of absent behavioural pain
reactivity during venepuncture (41.3% versus 8.7% of con-
(푃 < 0.05). This response (Delta heart rate) was significantly
reports of reduced pain sensitivity in ASD are related to a
different mode of pain expression rather than to an insen-
sitivity or endogenous analgesia. Plasma beta-endorphin
and heart rate before or after venepuncture (푃 < 0.05),
levels of plasma beta-endorphin is associated with behav-
ioural pain reactivity. In addition to the physiological
the venepuncture or other painful stimuli occurring at home
and day hospital (SIB, aggressive behaviours, stereotyped
ASD perceive pain, but do not express it in the same way that
control children do.
The findings by Tordjman et al.  also show that a sig-
nificant proportion of individuals with ASD did not display
low/absent overall pain reactivity according to the parental,
trols, 푃 < 0.0001), individuals with ASD displayed a signi-
ficantly increased heart rate in response to venepuncture
0.8 beats/min, 푃 < 0.05). This strongly indicates that prior
were positively associated with ASD severity (푃 < 0.001)
with the opioid theory of ASD that would suggest that high
greater than for controls (mean ± SEM; 6.4 ± 2.5 versus 1.3 ±
levels were higher in the ASD group (푃 < 0.001) and
but not with behavioural pain reactivity. This is inconsistent
(78%) of individuals with ASD were actually found to exhibit
normal behavioural reactivity to burning; highlighting the
importance of distinguishing different types of painful stim-
uli. Lastly, 22% of individuals with ASD displayed normal
behavioural pain reactivity to the venepuncture and 15.9%
subgroups within the ASD population. One subgroup may
other normal pain sensitivity. However, there are numerous
factors to consider when making such a conclusion at this
this present study found that the majority of individuals with
ASD exhibited normal pain reactivity to burning. It may be
that individuals with ASD may need to experience a parti-
cular high level of pain such as burning before they express
normal pain reactivity. However, when the painful event is
not so severe some individuals with ASD may have difficulty
in expressing the pain.
3.4. Pain Sensitivity Experienced in ASD. Klintwall et al.
 investigated sensory abnormalities in a population-
based group of 208 20-54-month-old children, diagnosed
with ASD and referred to a specialised habilitation centre for
early intervention. Children were subgrouped (eight in total)
based upon degree of autistic symptoms and cognitive level
by a research team at the centre. Parents were interviewed
systematically about any abnormal sensory reactions in the
child. In the whole group, pain and hearing were the most
the “Paris Autism Research In Sib-pairs” study, ) was
performed with one of the parents. This interview included
structured questions about the child’s sensory reactions to
light, sound, smell, and so forth. However, for the purposes
of this review their results for underreactivity to pain, under-
reactivity to heat, and underreactivity to cold are reported.
Only clinically significant sensory abnormalities were scored
as “present” in the study. Children in the most typical ASD
highest number of affected modalities. There were no group
groups of different cognitive levels or level of expressive
speech, supporting the notion that sensory abnormality is
very common in young children with ASD and providing
further justification for inclusion of this symptom in the
diagnostic criteria for ASD in the upcoming DSM-V. From
tivity to sound (44%) and underreactivity to pain (40%).
Underreactivity to cold and heat was reported for 22% and
7%, respectively. Interestingly, children with self-injurious
behaviours had a greater number of affected sensory abnor-
147); 푡(206) = 2.791, 푃 = 0.006. Therefore, this study pro-
malities (푀 = 2.0, SD = 1.5, 푛 = 61) compared to children
vides some support to the widely held belief that many
withnosuchself-injuriousbehaviours(푀 = 1.3,SD=1.2,푛 =
12 The Scientific World Journal
individuals (40%) with ASD are insensitive (under reactive)
Cascio et al.  recruited eight adults with high-
functioning ASD (clinical diagnoses of either Autistic Dis-
order or Asperger Disorder; DSM-IVTR; ); there were
seven males and one female (mean age 29.3 years, range 20–
45). Eight adults without ASD were recruited from the com-
munity, selected to match each individual with autism on age
and gender (mean age 29.0 years, range 21–45). Each partici-
pant completed a brief questionnaire, the Adult Sensory
Profile  to determine whether groups differed in terms of
their experience with sensory stimuli in everyday life. Cascio
pared to controls on two sites of the body: (1) the hairy
skin of the right dorsal forearm and (2) the glabrous skin
of the right thenar palm. A variety of tactile sensations were
investigated. However, for the purposes of this review only
those that were pain related are reported here. These were
the thermal sensation—cold pain and heat pain. Participants
a point of being “painfully or uncomfortably hot (or cold).”
In order to alleviate any anxiety about the pain stimuli, parti-
cipants were reminded that the device was limited to tem-
peratures that are too mild to produce skin damage, and that
their response triggered the return of the thermode to its
of 16.68∘C, compared to the control group average of 9.04∘C.
average threshold for the ASD group was 43.66∘C, while that
showed a greater degree of pain sensitivity to thermal pain at
both sites recorded in this study as this group’s cold and heat
pain thresholds were lower compared to the control group.
Bandstra et al.  examined self-reported and parent-
reported pain in 20 high-functioning youths with ASD (17
boys; 3 girls) and 20 typically developing controls (16 boys;
4 girls) ranging in age from 8 to 18 years and matched on age
and IQ. This is the first study to assess the self-report of pain,
with ASD. The Charleston Pediatric Pain Pictures (CPPP)
are a series of 17 cartoon pictures depicting scenes of med-
ical, play, and home situations . Each drawing has a cen-
tral figure of a young non-sex-specific child lacking facial
expression, who is engaged in an activity. Thirteen of the
17 scenarios depict pain-provoking events and each has a
short verbal vignette that describes the event taking place in
the picture. One example of the 13 pain scenarios was: “You
touched the hot stove and burned your hand. Show me how
much hurt you would have”. The amount of pain the part-
icipants would expect to feel was self-reported using the
Faces Pain Scale-Revised (FPS,  and a Numeric Rating
Scale (NRS) in a series of validated hypothetical pain situ-
ations depicted in cartooned images (e.g., scraping knee on
pavement). The FPS-R is comprised of 5 line drawings of
faces, presented horizontally, representing increasing levels
site(퐹 = 5.12,푃 = 0.0250),andgroup(퐹 = 3.84,푃 = 0.0518),
group 푥 session interaction (퐹 = 8.18, 푃 = 0.0048). The
with the ASD group displaying average cold pain thresholds
푃 < 0.01), and site (퐹 = 7.37, 푃 = 0.0073), and a significant
Forheatpain,therewasasignificanteffectofgroup(퐹 = 6.79,
of the control group was 46.58∘C. Overall, the ASD group
of pain, typically from no pain (0) to extreme pain (10). In
addition to the FPS-R, participants and their parents were
asked to rate the pain of the hypothetical situations using an
NRS. The NRS was provided using a 0 to 5 scale not only to
to provide participants with the same number of response
both the FPS-R and the NRS, whereas parents were asked
to only provide ratings of their child’s pain using the NRS.
Findings revealed no differences between the pain ratings of
youths with ASD or their parents as compared with a sample
of typically developing youths.
The lack of differences in pain intensity ratings between
the ASD and control youths in the study by Bandstra et al.
procedures [41, 62]. Discrepancies between different mea-
sures of pain (e.g., behavioural versus self-report measures)
are not unusual ; therefore it is possible that the self-
is also possible that youths with ASD, although experiencing
comparable levels of pain as typically developing children (as
evidenced by the current data), express their pain in a more
behaviourally and facially reactive manner (as evidenced
in prior research). However, despite these issues, Bandstra
et al.  highlighted the potential confounders that may
have been present in the other major studies which did find
increased facial pain response to the individuals with ASD.
Specifically the study by Nader et al.  was confounded
by its use of a bundling procedure (wrapping the child in a
blanket for the purpose of constricting movement during the
procedure) in preparation for the venupuncture procedure
for the group of individuals with ASD and not the control
group, a difference which could have accounted for the signi-
ASD as compared with the controls in that study . Also a
recent study showing greater behavioural response in child-
ren with ASD also found higher levels of a physiological
marker for stress in the ASD sample . This indicates the
possibility that the increased behavioural reactivity may not
be an expression of pain; rather they are distressed at under-
sider in trying to understand pain in individuals with ASD
nonverbal and low-functioning individuals with ASD, while
Nader et al.  omitted any information about the level of
functioningintheirsample. ThestudybyBandstraet al.,
on the other hand, used a high-functioning sample of child-
ren and adolescents with ASD. Also, Bandstra et al. 
investigated pain responses in children aged 8 to 18 years,
which represents a significantly older age group than the
participants included in the study by Nader et al. ), for
example, and aspects of the pain experience (e.g., ability to
ing children grow older . Similar to the youth ratings, no
The Scientific World Journal13
parent ratings of the amount of pain they would expect their
children to show. However, this finding does not necessarily
in this group may have grown accustomed to their children’s
idiosyncratic pain expressions (e.g., angry responses) over
time and have learned to interpret their child’s cues accu-
rately. Although group averages for parent and child ratings
were similar, additional correlations demonstrated a lack of
concordance between parent and child dyads which is not a
surprising phenomenon in paediatric pain assessment. This
finding may even provide further support for the argument
that the pattern between parent and child pain ratings is
consistent regardless of whether or not the child has ASD.
Furthermore, the lack of concordance in ASD is important
as it indicates that, as with typically developing children, it is
important for clinicians to gather pain intensity ratings from
youths with ASD, rather than only relying on parent report.
In their abstract, Daughters et al.  report their find-
ings of a pilot study they carried out to examine pain and
distress experienced by children with ASD during a dental
cleaning procedure. The authors hypothesised that children
with ASD would exhibit greater levels of behavioural distress
and pain during the dental procedure compared to control
uled for a dental cleaning procedure (without sedation) took
caregivers were asked to complete a behavioural checklist to
identify the severity of the child’s stereotyped behaviours,
cleaning procedures were videotaped and were later coded
using a variation of the Brief Behavioral Distress Scale
(BBDS), an observational measure of children’s procedure-
dren’s Pain Checklist-Revised (NCCPC) in order to assess
their child’s pain. The findings revealed that the mean pain
scores during the dental procedure were indicative of pain
for both groups. However, the children with ASD exhibited
greater pain scores (푀 = 29.8) than children without ASD
ren without ASD. There were also moderate associations
between severity of ASD symptoms and pain during the
(푀 = 10.0). Greater levels of interfering distress behaviour
behaviours (푟 = 0.43), with increased severity of the child’s
more sensitive to pain during dental cleaning procedures.
were exhibited in the children with ASD compared to child-
dental cleaning procedure (푟 = 0.55) and interfering distress
sum, this pilot study indicates that individuals with ASD are
symptoms relating to higher levels of pain and distress. In
3.5. Embodied Pain in ASD. Observing emotions or bodily
sensations in another individual produces brain activations
largely overlapping those which are activated during the
direct experience of the same feelings. This overlap in acti-
vated brain regions between observed and directly experi-
enced emotions or bodily sensations indicates that empathic
brain responses may rely on resonant, mirror-like systems
[80–82]. The idea that empathy for pain may be mediated
by mirror systems emerged with the finding that neurons
in the anterior cingulate cortex (ACC) fire in response to
both pain in the self and the observation of pain in another
. Although ASD are often described in terms of reduced
empathic abilities , evidence for reduced empathy in
domains different from mentalising and perspective taking
(for instance pain) is sparse. To investigate this, Minio-
with Asperger’s Syndrome (a type of ASD) (aged 28.0 ± 7.2
Minio-Paluello et al.  used single-pulse transcra-
nial magnetic stimulation (TMS) to explore a rudimentary
form of empathy, called “sensorimotor contagion”, elicited in
neurotypical participants when they observe painful stimuli
applied to the body of another person. The authors regard
sensorimotor contagion to have taken place when there
is a reduction of corticospinal excitability recorded from
the specific body part that is vicariously affected by the
observed painful stimulation, in this case, the hand muscles.
This inhibition to observation of pain inflicted on another
body is characteristic of the corticospinal inhibition found
during actual noxious stimulation (when the pain is directly
inflicted). So in the study carried out by Minio-Paluello et al.
vation of painful and nonpainful stimuli affecting another
single-pulse TMS of the left primary motor cortex (M1)
were simultaneously recorded from two right-hand muscles,
the first dorsal interosseous (FDI), and the abductor digiti
“static”: static right hand; (2) “Pain”: needle deeply penetrat-
the FDI region; and (4) “Tomato”: needle deeply penetrating
a tomato. Thus, whereas participants’ FDI muscle was vicar-
iously involved by the painful stimulation, the ADM muscle
served as a somatotopic control because it was not shown to
be penetrated. Previous studies of TMS show that watching
the video were static in the clips and the syringe holder was
not visible. In addition to these objective neurophysiological
measures, participants were also asked to imagine how the
pain would feel, if applied to them. The qualities of the imag-
ined pain were measured using the McGill Pain Question-
naire (MPQ) , which is made up of Sensory (items 1–10,
17–19) and Affective (items 11–15, 20) subscales, and through
the Hurts value, a rating between 0 and 10 indicating how
Minio-Paluello et al.  found that when observing
other’s pain, participants with ASD, in contrast to neurotypi-
cal control participants, did not show any amplitude reduc-
tion of motor-evoked potentials recorded from the muscle
vicariously affected by pain, nor did their neurophysiological
response correlate with imagined pain sensory qualities. All
experimental video clips were similarly rated by the two
years) and 20 neurotypical controls (aged 25.3 ± 6.7 years)
age, sex, and IQ matched.
groups (푝푠 > 0.10) except for the Static condition, which was
significantly less arousing for ASD (푃 < 0.02). Participants
14 The Scientific World Journal
with ASD, compared with control participants, perceived
(푡 = 2.07, 푃 = 0.050) and tended to judge the touch as
shown in the videos and to rate the sensory and affective
qualities of imagined pain, control participants and individ-
more painful (푡 = −1.82, 푃 = 0.08). When asked to imag-
ine how they would feel if receiving the painful stimulation
uals with ASD gave similar ratings (all 푝푠 > 0.33). There-
of the observed events. They were therefore able to correctly
understand or identify how painful a particular event would
be despite showing abnormal neurophysiological responses.
the observation of painful stimuli inflicted to the hand mus-
cle of another person inhibited control participants’ corti-
cospinal representation of the same muscle (i.e., the FDI
modulated cannot be explained in the terms of reduced reac-
tivity of this muscle. Indeed, when videos depict the ADM
being penetratedby a needle,similarcorticospinalinhibition
of this muscle has been observed . In sum, finding no
embodiment of others’ pain or reduced empathic abilities in
sorimotor contagion during the observation of pain affect-
ing another person, the hand in the movie clips) provides
in people with ASD and suggests that their difficulties with
empathy is mediated not only by cognitive dimensions but
also by sensorimotor resonance with others.
fore the lack of sensorimotor contagion in ASD cannot be
explained by group differences in the imagined “painfulness”
3.6. Relationship between Opioid Hormone and ASD.
Nagamitsu et al.  measured cerebralspinal fluid (CSF)
levels of beta-endorphin, an opioid hormone, in 19 Japanese
children (17 boys, 2 girls, mean age 4.23 years, range 2.00–
iour (3/19), pain insensitivity (8/19), and stereotyped move-
ments (10/19). The controls consisted of 23 age-matched
Japanese children (18 boys, 5 girls, mean age 3.78 years, range
0–10.75) who had undergone lumbar puncture for the diag-
nosis of a possible central nervous system (CNS) infection
but whose CSF showed normal results. CSF levels of p-endo-
rphin in three patients with the Rett syndrome (3 girls, ages
10–14 years) who presented with symptoms resembling those
of infantile ASD were also recorded. In infantile autism, CSF
levels of beta-endorphin did not differ significantly from
those of age-matched controls. No significant correlation
between CSF levels and clinical symptoms, including self-
injurious behaviour, pain insensitivity, and stereotyped
movement was found. However, CSF beta-endorphin levels
were significantly higher in the patients with Rett syndrome
than in the control (푃 < 0.05). Findings indicated that neu-
relationship between dysfunction of brain opioid and ASD.
rons containing beta-endorphin may not be involved in
patients with infantile autism, therefore not supporting the
3.7. Oversensitivity to Pain and Age of Diagnosis of ASD.
Mandell et al.  attempted to identify factors which may
delay diagnosis of ASD among a community sample of
from 969 caregivers of children who had ASD and were
disorder, 3.9 years for pervasive developmental disorder not
otherwise specified, and 7.2 years for Asperger’s disorder
(a type of ASD). Interestingly, oversensitivity to pain was
associated with a 0.6-year increase in the age of diagnosis.
The association of oversensitivity to pain with later diagnosis
other organic causes and not consider developmental issues.
imental Studies. Of the five case studies only one specifies
level of functioning and was mild ASD . The remaining
four case studies do not indicate level of functioning [32, 33,
56, 58]. Of the ten experimental studies, two studies include
did not specify level of functioning [70, 79, 88]. One did
not specify low or high functioning using clinical guidelines
and examined a variety of ASD symptoms to determine
a level of functioning but does not report how many are
contained within each category . Another study, rather
levels of severity based on scores on the Autism Spectrum
employed The Childhood Autism Rating Scale (CARS, )
to create two groups: severely autistic and mildly-moderately
autistic and the majority of the group fell into the severely
group, assessing ASD severity using the Autism Diagnostic
Interview-Revised (ADI-R, ). . Four of the experi-
mental studies did not include a comparison/control group
[46, 70, 79, 89].
Five case studies and ten experimental studies were found in
the PRISMA search which investigated some aspect of pain
in individuals with ASD. All five case studies described indi-
viduals with ASD who were exhibiting pain insensitivity [17,
32, 33, 56, 58]. The two cases presented by Bursch et al. 
perseverative focus of attention for individuals with an ASD.
can serve to increase pain and associated distress. Therefore,
implementing a treatment that somehow interrupts the per-
severation might reduce or even eliminate the pain that the
Schlank  found. They describe a case in their pain clinic
where a child with ASD presented to them yelling repeatedly,
“Ow! Ow! Ow!” Two months earlier, the child had sustained
a leg injury and he had been shouting ever since. Zeltzer
and Schlank suggested that rather than shouting, the child
should replace this by squeezing a ball instead. Interestingly,
this resulted in a transfer of his expression to the point where
he actually reported feeling better because he no longer felt
The Scientific World Journal15
strongly indicate that treating the perseveration can be the
most effective way to reduce suffering for some patients .
in children with ASD the anxiety often experienced by this
remain tense for extensive durations .
Also important for clinical practice is the case study by
Mieres et al.  which suggests a particular approach is
required in assessing the subjective feeling of pain in indi-
viduals with ASD. Rather than ask how much pain they are
verbal and pictorial pain scale).
Of the ten experimental studies only one found no
found between the pain ratings of youth with ASD or their
parents as compared with a sample of typically develop-
ing youths . Interestingly, overall, only one of the experi-
evidence of underreactivityto pain(suggestive ofpaininsen-
sitivity) in 40% of their sample . One study  found
thatindividualswithASDdo nothaveadecreased sensitivity
for pain and investigated both behavioural reactivity to pain
during venepuncture as well as plasma b-endorphin concen-
behavioural pain reactivity in the individuals with ASD dur-
ing venepuncture despite their higher heart rate and plasma
b-endorphin levels—strongly suggesting that the individuals
with ASD were not insensitive to pain.
Five studies found evidence of a greater degree of pain
sensitivity in individuals with ASD [62, 72, 79, 85, 89]. Inter-
increase in the age of diagnosis . One study  investi-
gated the influence of information about the pain experience
of children with ASD on observers’ judgement of pain inten-
sity in children with ASD and examined the impact of facial
activity on observers’ judgement of pain intensity in child-
ren with ASD. Facial activity was found to have a significant
impact on observers’ estimates of pain intensity; pain sensi-
tivity information did not . This is in contrast to the view
that parents’ ratings of pain in their children with ASD may
be distorted due to misinformation about pain insensitivity
terms of investigating the effect of information of pain sen-
sitivity in individuals with ASD, is that the students in this
study had no personal relationship to the individuals they
to the lack of effect of pain information on the judgments
made. A different picture might emerge if the same situation
was applied to individuals with a personal relationship to the
child such as a parent. These results have important impli-
cations for the assessment and management of pain in child-
ren with ASD . The finding that observers may be able to
because children with ASD frequently lack the skills to
express their pain verbally and this could put them at risk for
substandard health care. The findings of a significant behav-
ioural reaction in response to a painful stimulus in individu-
als with ASD [62, 72, 79, 85, 89] contradict the widespread
belief in the literature of pain insensitivity in individuals
with ASD. Some of the findings reported in this review also
as an assessment tool for pain in children with ASD .
Another study investigated whether P-endorphin plays an
important role in infantile autism by measuring the cerebro-
spinal fluid (CSF) levels of p-endorphin and evaluated the
correlation between these levels and ASD symptoms .
Findings did not support the opioid hypothesis to explain
pain sensitivity in ASD .
Another important aspect is whether the five experimen-
tal studies that included different levels of functioning or
notable effect on the results. For instance, were the findings
weaker for individuals who are higher functioning. Two
were positively associated with ASD severity. Minio-Paluello
et al.  found that corticospinal inhibition was maximal in
the individuals with fewer ASD traits.
4.1. Expression of Pain in Individuals with ASD. Numerous
anecdotal reports show that caregivers frequently describe
unusual, or absent, responses to painful stimuli in their
children with ASD. Some caregivers are even able to describe
unique behaviours in their child that enable them to know
when they are in pain. However, it is crucial to point out here
that altered pain expression is not universally observed in
experience appears different in individuals with ASD .
Tordjmanet al.  argue thattheirfindings indicatethat
prior reports of reduced pain sensitivity in ASD are related,
not to an insensitivity or endogenous analgesia to pain but
to a different mode of pain expression. This is without doubt
the most crucial finding and clearly further investigation to
explore this aspect is required. The findings by Tordjman et
al.  constitute a clear challenge to theories of reduced
pain sensitivity in ASD since they found that painful stimuli
can produce physical and psychic stress in individuals with
ASD and that this stress can be manifested by physiological
responses and expressed through autistic behaviours. Tord-
jman et al.  hypothesise that the different mode of pain
expression in individuals with ASD may be mediated by
(1) verbal communication impairments, (2) deficits in non-
verbal communication and body image problems (difficulty
locating the painful area), or (3) other cognitive problems
such as (a) difficulty in establishing cause-effect relationships
(b) problems discriminating, representing and identifying
rial, emotional, and cognitive factors ), (c) problems of
learning socially appropriate responses to pain .
The majority of the experimental studies included in
the review examine pain reaction to a specific medical
16 The Scientific World Journal
procedure venepuncture. Therefore, the findings cannot be
during everyday situations and experience of chronic pain in
individuals with ASD. It is also important to acknowledge
that the experiences of children with ASD occur along a
spectrum of severity. Therefore it is highly possible that the
experience and expression of pain may differ depending on
where the individual lies on this spectrum (Messmer et al.
); the level of communicative and language abilities of
individuals  and the impact of different ASD diagnoses
expression and reactivity. This variability again emphasises
that interventions and treatments must be tailored to each
specific child .
Despite the complexity in interpreting the findings from
sensitivity in individuals with ASD, what is clear is that there
is a need for a pain assessment tool specifically for use in this
population . Existing instruments may be inappropriate.
To my knowledge, there has only been one study (from a
dissertation submitted to the University of Florida for the
degree of Doctor of Philosophy) which has attempted to
identify whether there are unique pain indicators applicable
to a significant amount of children with ASD and whether
pletely unique to the one child. Inglese  found several
objective, observable and measurable indicators which were
presumed by the author to be relevant to pain assessment in
ASD (i.e., “furrowed brow,” “banging his/her head,” “injuring
oneself,” “grimacing,” “guarding,” and “increased heart rate”),
(a) knowledge of the child’s baseline, and (b) monitoring for
changes from normal (i.e., “crankiness,” “being less active,”
“rocking unusually,” “acting “off”, and “irritability”). Inglese
 suggests then that in the designing of a new instrument
needs to be the inclusion of sections which are objective and
quantifiable—these could be used by individual(s) who are
unfamiliar to the child being assessed—in addition to sec-
information regarding their child’s baseline and objective
assessment questions which can be conducted by individuals
unfamiliar with the child is crucially important in creating a
comprehensive pain assessment in this population .
4.2. Limitations. Sensations are often thought to be logically
private, subjective, self-intimating, and the source of incor-
rigible knowledge for those who have them. Since pain
is often thought to be a “subjective” experience, this has
lead researchers to use the report as the gold standard for
pain experience. Many of the studies identified in the pre-
sent review investigate pain reactivity using caregiver reports
which have obvious limitations such as reporting bias. How-
ever, the most notable limitation with this is highlighted by
research which suggests that parents of children with ASD
tion task. For instance, in an emotional labelling task in
response to schematic facial patterns representing five basic
emotions, parents of children with ASD performed worse
than parents of control children (i.e., ). The study by
consistent with the difficulties found in parents of children
with ASD in correctly interpreting facial emotions. Nader
et al.  found that some of the caregivers did not interpret
their child’s pain expression accurately in that children with
ASD who had been assessed by their parents as having a
lower pain sensitivity and reactivity tended to show greater
facial reactions and behavioural distress in response to the
Similarly, there is the issue of asking individuals with
ASD to rate pain according to facial expressions of pain (i.e.,
Faces Pain Scale (FPS)). Numerousresearchers maintainthat
individuals with ASD have difficulty with processing facial
expression (i.e., ). Individuals with ASD process faces
differently and show reduced attention to faces and facial
expressions . This reduced interest in faces is likely to
impair their face processing skills, so that children with ASD
do not become “face experts” like their typically developing
The majority of the small number of studies which
investigated some aspects of pain specifically in individuals
with ASD are limited by their sample size. Seven of the ten
experimental studies had sample sizes of ASD groups less
with ASD. More studies with larger sample sizes examining
behavioural reactivity to pain as well as measuring physio-
experience in individuals with ASD. A further complication
in attempting to draw conclusions from the literature to
date are the differences across studies in terms of cognitive
development of the individuals with ASD (not to mention
patientswerecognitivelyimpaired:meanfullscaleIQ = 42.2,
ficant problem when trying to determine whether there is
pain insensitivity, greater pain sensitivity or no difference in
individuals with ASD.
Lastly, it is also difficult to disentangle from the exper-
imental studies conducted to date as to how much of the
observed pain reactions, and so forth were due to the indi-
viduals with ASD level of distress rather than any pain
response. Individuals with ASD might display more distress
during the venepuncture procedure compared to controls
and this might be completely independent from how painful
they find the experience.
SD = 3.2 (range 40–58) while another study all had IQ of at
least 70 . These limitations and differences pose a signi-
ies are needed to recognise illnesses earlier in the absence
of pain or pain perception in children with an ASD and to
develop reliable and valid metrics for pain identification for
both verbal and nonverbal individuals with ASD . Fur-
ther research is also needed to explore the concordance
between parent report of pain sensitivity and observed reac-
tivity of children with ASD to every day painful incidents.
to procedural pain in a clinical setting but atypical responses
The Scientific World Journal17
tant to understand how different types of pain in different
settings are perceived in order to acceptably manage pain
in children with ASD. Additionally, more research is needed
to understand how observers decode the pain experience of
children with ASD and explore the potentially biasing effect
of pain sensitivity information on observers’ estimates of
pain in children with ASD . The study by Mieres et al.
 also stresses the importance of the way in which clini-
cians ask patients with ASD about how much pain they are
experiencing. They found that asking the individual with
ASD how uncomfortable they were on a scale of 1 to 10 was a
more accurate representation of the pain they felt than when
they were asked directly how much pain they were in on a
scale of 1 to 10.
ren and adults with ASD react to various types (acute versus
chronic) or degrees of pain. The need for this research is
emphasised by the study reported in this review  that a
significant number of individuals with ASD reported absent
reactivity to burning based on caregiver report. This clearly
when studying pain in this population.
In a study just published, Wager et al. , based on
fMRI-based measure that predicts pain intensity at the level
of the individual person and found that it is possible to use
fMRI to assess pain elicited by noxious heat in healthy per-
(for instance the reliability of self-report measures of pain
and caregiver report of pain in their child), this would be an
more robust and objective way to investigate whether pain
to controls. This might also have the potential to show
whether there is a discordance between neural signatures of
pain and the expression of pain in the individual with ASD.
There is still relatively little research on the unique problems
posed by the expression of pain and sensitivity to painful
stimuli in individuals with intellectual and developmental
disabilities  and particularly in individuals with ASD
from childhood to adulthood. Overall, the findings reported
here of a significant behavioural reaction in response to a
painfulstimulusin individualswith ASD contradict the wide
spread belief in the literature of pain insensitivity in indi-
viduals with ASD. The case studies all reported pain insen-
sitivity in individuals with ASD and provide an example of
how impaired sensory perceptions can mask and delay the
ability of health care professionals to recognise the need for
treatment. However, the majority of the ten experimental
studies reviewed here indicate that the idea that individuals
with ASD are pain insensitive needs to be challenged. This
others, and have an indifference to pain and a high threshold
this review is the importance of further study to explore the
from that of neurotypicals. Recognition of all these findings
have important implications for the treatment and recogni-
tion of the need for treatment in individuals with ASD.
Conflict of Interests
The author declares no conflict of interests.
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