Chronic Pain and Neuropsychological Functioning

P1: FVI,FMN/FGL P2: FNN
Neuropsychology Review Pl164-899 July 20, 2000 12:4 Style le version March 18, 1999
Neuropsychology Review, Vol. 10, No. 3, 2000
Chronic Pain and Neuropsychological Functioning
Robert P. Hart,
1,3
Michael F. Martelli,
2
and Nathan D. Zasler
3
This review article examines the effect of chronic pain on neuropsychological functioning. Primary
attention is given to studies that include patient groups without a history of traumatic brain injury
(TBI) or neurologic disorders. Numerous studies were identied that demonstrate neuropsychological
impairment in patients with chronic pain, particularly on measures assessing attentional capacity,
processing speed, and psychomotor speed. Despite suggestive ndings, further studies are needed to
clarify the variables that mediate the impact of pain on neuropsychological functioning and the unique
role of various symptoms often associated with chronic pain.
KEY WORDS: Chronic pain; neuropsychological functioning.
INTRODUCTION
In the current paper, we review studies that exam-
ine cognitive functioning in patients with chronic pain.
Pain, as dened by the International Association for the
Study of Pain (IASP), is an unpleasant sensory and emo-
tional experience associated with actual or potential tissue
damage, or described in terms of such damage. Pain is
generally considered a multidimensional subjective expe-
rience mediated by emotion, attitudes, and other percep-
tual inuences. Variability in pain responses are common
and appear to reect complex biopsychosocial interac-
tions between genetic, developmental, cultural, environ-
mental, and psychological factors (Hinnant, 1994; Turk
and Holzman, 1986).
Acute pain, or pain occurring shortly after injury,
is typically characterized by (a) relatively discrete neu-
roanatomic pathways mediating effects of somatic injury;
(b) transmission of information with survival value that
initiates protective physiological mechanisms (against in-
jury extension) and signals the need for corrective action
to promote healing; (c) a time-limited course during which
treatment is aimed at correcting the pathological process;
and (d) the relative absence of marked psychosocial
1
Medical College of Virginia of Virginia Commonwealth University.
2
Concussion Care Centre of Virginia, Ltd.
3
Pinnacle Rehabilitation, Tree of Life, LLC, Richmond, Virginia.
4
To whom correspondence should be addressed at Department of Psy-
chiatry, Medical College of Virginia of Virginia Commonwealth Uni-
versity, P.O. Box 980268, Richmond, Virginia 23298-0268.
changes or behavioral changes disproportionate to pain
intensity. In contrast, chronic pain persists long after in-
jury (i.e., typically 6 months) and is more likely to be
characterized by (a) relatively ambiguous neuroanatomic
pathways mediating somatic effects; (b) transmission of
information that may perpetuate protective responses of
limited adaptive value especially to the extent that there is
a lack of underlying tissue damage and/or decreases in, or
avoidance of, activity, inhibiting rehabilitation; (c) a pro-
tracted course of medication use and minimally effective
medical services; and (d) marked behavioral and emo-
tional changes, including restrictions in daily activities.
Importantly, avoidant behavior and reduced activity level
often associated with ineffectively treated chronic pain
are likely to result in a cyclic disability-enhancing pattern
of further decreased activity and avoidance that prevents
normal restoration of function and perpetuates painful ex-
perience. The longer pain persists, the more recalcitrant it
generally becomes and the more treatment goals focus on
coping with pain and its concomitants (Kulich and Baker,
1999; Martelli, Grayson, and Zasler, 1999).
In this review, primary attention is given to studies
that include patient groups without a history of traumatic
brain injury (TBI) or neurologic disorder in order to ex-
amine the potential contribution of persistent pain and
associated symptoms to impaired performance on neu-
ropsychological tests. An understanding of the effects of
pain on cognitive functioning has important implications
for appreciating the range of problems reported by pa-
tients with pain syndromes, for differential diagnosis, and
131
1040-7308/00/0900-0131$18.00/0 C
2000 Plenum Publishing Corporation
132 Hart, Martelli, and Zasler
for evaluation in cases of atypical presentation by pa-
tients with brain impairment. Understanding the range of
problems associated with chronic pain seems imperative
when its prevalence in the general population is consid-
ered. Conservative estimates of frequency of some type
of chronic pain in the U.S. population range from 35 to
75 million (Walsh, Dumitu, Ramanurthy, and Schoenfeld,
1988). With regard to differential diagnosis and atypical
clinical presentations, a particularly important example is
that of persistent complaints following presumptive mild
TBI. In this case, diagnosis is typically based on neu-
ropsychological test ndings as the most sensitive sign of
brain injury. The judgments made have far-reaching im-
plications in terms of nancial, vocational, treatment, and
disability issues. Traumatic injuries frequently affect mul-
tiple parts of the body, although headache is the most fre-
quent symptom following injury to the head and/or neck,
with an incidence rate estimated at 90%and persistence at
6 months as high as 44% (Martelli, Grayson et al.,1999).
The validity and utility of neuropsychologically based in-
ferences in the case of mild TBI necessarily depend on
assurances that the effects of pain are considered when
interpreting results.
From the perspective of the clinician referred a pa-
tient for evaluation, possibilities to consider include pain
exacerbating decits from a known CNS disorder or pain
causingdecits that, inturn, raise concernabout anuniden-
tied CNS disorder. For example, Vernon-Wilkinson and
Tuokko (1993) studied 122 consecutive TBI referrals for
assessment. They contrasted the performance of those
TBI patients who either complained of pain as an im-
portant problem or who exhibited pain behaviors, and
those who did not. Despite the fact that the pain group had
suffered less severe injuries as assessed by the Glasgow
Coma Scale, length of posttraumatic amnesia, and ven-
tricular enlargement on CT scan, these patients exhibited
greater cognitive impairment. Patients with pain symp-
toms performed less well on tests of intelligence, rea-
soning, and memory (WAIS-R Performance I.Q.; Ravens
Progressive Matrices; Category Test; and Benton Visual
Retention Test). The patients with pain symptoms also re-
ported higher levels of psychological distress on symptom
inventories, although the authors did not examine whether
psychological distress was an important mediating vari-
able. As an example of pain-related deciencies in the
absence of other identiable causes, Jarvis and Kooken
(1998) describe a patient diagnosed with bromyalgia
who had no history of head injury, neurologic disorder,
substance abuse, or psychiatric disorder. The patient had
been taking a low dose of Elavil for relief of insomnia
and part way through the test session reported increased
pain and appeared fatigued. The patients performance
was remarkable for problems on tests requiring attention
(e.g., Trail-Making Part B; WAIS-R Digit Symbol; Digit
Span; Seashore Rhythm Test; and Speech Sounds Percep-
tion Test).
OVERVIEW OF STUDIES
Table I summarizes the clinical studies that included
a group of chronic pain patients without neurologic dis-
orders or injuries involving head trauma or loss of con-
sciousness (one study in which 13% of the sample had
a short loss of consciousness is included). The table in-
cludes information on clinical characteristics, comparison
groups, medication status, litigation status, use of pain
ratings, measures of emotional status, and a list of tests
found to be sensitive versus insensitive to the performance
changes in pain patients and/or to pain intensity level.
The large majority of studies included patients with
either chronic pain syndromes involving mixed or mul-
tiple sites, or whiplash injuries. The type of pain (e.g.,
myofascial) was often unspecied. Some studies focused
on specic pain syndromes such as bromyalgia, rheuma-
tism(Barr e-Lieou Syndrome), or temporomandibular dis-
order (TMD). Approximately half (11/23) of the studies
summarized in the table involved comparisons to a normal
control group, and some of these studies included addi-
tional contrasts (e.g., high vs. low pain groups, pain vs.
TBI sample, pain vs. depressed sample). Almost all of
the remaining studies relied upon normative data, and in
about half of these studies comparisons were also made
to a TBI sample. A few studies compared high-low pain
subgroups, contrasted patients pre- and post-treatment, or
compared pain patients to another clinical group without
using normal control subjects or referring to normative
data. Many of the studies assessed emotional status or
used symptom inventories that included such items as fa-
tigue or sleep disturbance, as well as items pertaining to
mood state/emotional distress. However, many of them
did not explore the relationship between these variables
and neuropsychological test performance. Brief sections
on nonclinical samples, patients with CNS disorders, and
neurophysiological correlates of chronic pain are included
to highlight relevant issues rather than provide a compre-
hensive review of the literature.
NEUROPSYCHOLOGICAL FINDINGS
IN CHRONIC PAIN POPULATIONS
There are relatively few data available to help the
clinician estimate the likelihood that chronic pain might
be a factor contributing to neuropsychological decits.
Chronic Pain 133
Table I. Summary of Studies
TBI or CNS
Authors Clinical groups disorder Normal controls Medication Litigation
Bell, Primeau,
Sweet, and
Loand (1999)
Chronic pain syndromes
(n = 20)
No No >50% seeking
compensation
Cote and Moldofsky
(1997)
Fibromyalgia (n = 10)
Patients with a psychiatric
disorder were excluded
No n = 9 No patients taking
medication at the time
DiStefano and
Radanov (1995)
Whiplash injury patients
symptomatic at 2-year
follow-up (n = 21)
No patient had
head contact
injury or
alteration of
consciousness
No 19% using medication
that might inuence test
performance
No patient initiated
litigation during
follow-up period
Eccleston (1994) Chronic benign pain at
mixed sites
Study 1 (n = 20)
Study 2 (n = 24)
No Study 1 (n = 10)
Study 2 (n = 12)
Intermittent use of
opiate-based analgesics
Study 140%
Study 236%
Eccleston (1995) Chronic intractable

benign pain at mixed
sites (n = 22)
No n = 11 45% opiates
Eccleston, Crombez,
Aldrich, and
Stannard (1997)
Chronic pain at mixed sites
(n = 46)
No No 13% opioid medication,
24% combination of
nonsteriodal analgesic,
antidepressant or opioid
medication
Gimse, Bjorgen,
Tjell, Tyssedal,
and Bo (1997)
Chronic whiplash patients
with disturbances in the
posture control system
(n = 23)
13% had a short
period of
unconsciousness
at the time of
injury
n = 26 Yes 13% in litigation,
48% awaiting
compensation from
insurance
Goldberg et al.
(1996)
Chronic TMD post whiplash
injury (n = 13), Chronic
idiopathic TMD (n = 14)
Whiplash
patients did
not experience
loss of
consciousness
at injury
No No patients taking
medication known to
affect CNS functioning
Virtually all subjects
recruited following
adoption of no fault
insurance
Grace, Berg, and
Nielson (1995)
Fibromyalgia (n = 15) No n = 15 No patients taking
medication known to
Grace, Nielson,
Hopkins, and
Berg (1999)
Fibromyalgia (n = 30)
Patients with clinical
depression were excluded
No n = 30 Approximately half the
patients taking
antidepressants or
anxiolytics, but none
taking a narcotic
analgesic
Grigsby, Rosenberg,
and Busenbark
(1995)
(n = 19)
Pain was myofascial for
nearly all 42% had
whiplash injuries
No No No patients taking
medications known to
Kaplan, Meadows,
Vincent,
Logigian, and
Steere (1992)
Fibromyalgia (n = 11) No No
Kewman,
Vaishampayan,
Zald, and Han
(1991)
Musculoskeletal pain at
mixed sites (n = 73)
No No Excluded patients taking
narcotic analgesics day
of exam
Landro, Stiles, and

Sletvold (1997)
Fibromyalgia (n = 25) No n = 18
Lorenz, Beck, and
Bromm (1997)
(n = 6)
No No No patients with routine
use of opioids
Pincus, Fraser, and

Pearce (1998)
(n = 20)
No n = 20
(Continued )
Table I. (Continued)
TBI or CNS
Authors Clinical groups disorder Normal controls Medication Litigation
Radanov et al.
(1993)
Whiplash injury patients
symptomatic at 6-month
follow-up (n = 31)
No patients had
head contact
injury or
alteration of
consciousness
n = 10 Yes Patients covered by
insurance that
compensates for
economic loss and
none initiated
litigation during
follow-up
Radanov, Dvorak,
and Valach (1992)
Chronic whiplash injury
with upper cervical
syndrome (UCS; n =
30), chronic whiplash
injury with lower
cervical syndrome
(LCS; n = 15)
43% with UCS
but none with
LCS reported
short duration
impairment of
consciousness
at injury
prescribed medication
20% completing tests
examined in
connection with
insurance claims
Radanov, Hirlinger,
DiStefano, and
Valach (1992)
Cervical spine syndrome
from rheumatism
(n = 28), chronic
whiplash injury (n = 54)
Whiplash
patients did
not suffer
head trauma
or a loss of
consciousness
prescribed medications
Schmand et al.
(1998)
Chronic whiplash injury
(n = 108; 43 scored
below cutoff on
malingering test and were
a separate group)
Patients with
TBI or loss of
consciousness
were excluded
from whiplash
group
n = 46 31% analgesics, 7%
benzodiazepenes, 2%
combination of above
33% evaluated as
part of litigation,
89% with damage
claim or workmans
compensation claim
Schwartz et al.
(1987)
Mixed chronic pain
syndromes (n = 17)
No No 18%
Sletvold, Stiles, and
Landro (1995)
Fibromyalgia (n = 25) No n = 18
Taylor, Cox, and
Mailis (1996)
Chronic pain
syndromes (n = 24),
chronic whiplash injury
(n = 15)
Whiplash
patients did
not suffer impact
injuries or a loss
of consciousness
No No patient taking
medications known to
Whiplash patients
had been referred for a
medical-legal
evaluation
Assessment of Tests sensitive to Tests not sensitive
Authors Pain ratings emotion effects of pain to effects of pain Other ndings
Bell, Primeau,
Sweet, and
Loand (1999)
7-point scale Beck Depression
Inventory
On battery of tests 15% of
pain group performed
at a low level expected
in only 5% of normals,
while 30% of group of
mild TBI patients did
so ( p < .05)
Cote and Moldofsky
(1997)
7-point scale for each of 10
anatomical regions
Beck Depression
Inventory
Mood scale
adapted from
U.S. Naval
Health Research
Centers Mood
Scale
Simulated
multitask
ofce
procedure
Speed of serial
addition/
subtraction?
Speed of
grammatical
reasoning?
Simple RT
Short-term
spatial memory
Pain patients were
impaired in speed of
response, but not
accuracy, on several
tests from a
computerized battery.
Patients showed lighter
sleep (stage 1) on
polysomnography.
Stage 1 sleep and
somatic components of
the Beck Inventory
covaried with aspects of
test performance
(Continued )
Chronic Pain 135
DiStefano and
Radanov (1995)
010 scale Well-being scale PASAT
TMT
Digit span
Corsi-Block
Tapping
Number
Connection Test
CVLT
Symptomatic patients
performed worse than
asymptomatic on
PASAT. Scores on
PASAT covaried
with pain intensity
Eccleston (1994) Visual analog scale and
numerical rating scale
Short-form
McGill Pain
Questionnaire
Numerical
interference
task-
nondominant
response
condition (see
text)
Numerical interference
task-dominant response
condition
Patients with high pain
intensity performed
worse than those with
low pain intensity and
normal controls.
Medication status not
related to performance
Eccleston (1995) Visual analog scale and
numerical scale
Hospital Anxiety
and Depression
(HAD) Scale
Numerical
interference
task in which
subjects
switch
(uncued)
between
dominant and
nondominant
response
conditions on
each trial (see
text)
Patients with high pain
intensity performed
worse than those with
low pain intensity and
normal controls.
Medication status and
mood were not related
to performance
Eccleston, Crombez,
Aldrich, and
Stannard (1997)
Visual analog scale and
numerical rating scale
Hospital Anxiety
and Depression
(HAD)
Scale
Zung
Modied Somatic
Perceptions
Questionnaire
Numerical
interference
task-difference
in reaction
time between
dominant and
nondominant
response
conditions
(see text)
Patients with both high
pain intensity and high
somatic awareness
those with other
combinations (i.e.,
high-low) of pain
intensity and somatic
awareness, and
reported more mood
disturbance
Gimse, Bjorgen,
Tjell, Tyssedal,
and Bo (1997)
No No RAVLT
PASAT
(prolonged
ISI)
PASAT (standard ISI)
TMT Letter/Category
Fluency
WAIS-R Block
Design and
Similarities
Whiplash patients
normal controls.
Subgroups with vs.
without premorbid
health problems and/or
current medication use
did not differ from one
another
Goldberg et al.
(1996)
Evoked pain reaction to
palpation on 03 scale
Symptom
checklist-90
Revised
(SCL-90R)
Simple/choice
RT
Consonant
Trigrams?
CVLT
(immediate)?
Whiplash TMD group
idiopathic TMD group
on tests of reaction
time, CVLT
(immediate but not
delayed recall) and
Consonant Trigrams
Grace, Berg, and
Nielson (1995)
No No WMS-R General
Memory Index
WMS-R Attention
Concentration
RAVLT Total recall
trials 15
PASAT trials 12
Pain patients reported
sleep disturbance
relative to controls on
the Pittsburgh Sleep
Quality Index
(Continued )
Grace, Nielson,
Hopkins, and
Berg (1999)
Pain Severity Scale from
Multidimensional Pain
Inventory
State-Trait Anxiety
Centre for
Epidemiological
Studies
Depression
Scale (CES-D)
WMS-R General
Memory and
Delayed
Recall
Indices
PASAT
WMS-R Attention
Concentration
Index
RAVLT Total
recall trials 15
Symbol Digit
Modalities Test
Pain patients reported
more sleep disturbance
on Pittsburgh Sleep
Quality Index, and self-
rated memory problems
that exceeded objective
decits. Pain intensity
and trait anxiety
correlated with tests
and partial correlations
indicated anxiety as a
primary factor
Grigsby, Rosenberg,
and Busenbark
(1995)
No No Simple/choice
RT
Short-term visual memory
(see text)
Pain patients were
impaired based on
norms, and also
performed less well on
than a group of mild to
moderate TBI patients
Kaplan, Meadows,
Vincent,
Logigian, and
Steere (1992)
No Beck Depression
Inventory
MMPI
Pain patients performed
similar to depressed
patients on memory
tests, but both groups
tended to do worse than
a group with
encephalopathy related
to Lymes Disease
Kewman,
Vaishampayan,
Zald, and
Han (1991)
5-point scale and visual
analog scale
Visual analog
scales of mood
and energy level
Neurobehavioral
Cognitive
Status
Examination
32% had impaired
performance.
Composite score
correlated with ratings
of pain and disability,
and measure of
psychological distress
Landro, Stiles, and
Sletvold (1997)
Visual analog scale Beck Depression
Inventory
Randt Memory
Test
Code Memory
Test
Word Fluency
Digit Span
Kimura Recurring
Figures Test
Incidental Memory
(RANDT)
Pain patients with a
history of major
depression were
impaired on memory
tests, but those patients
without a history of
depression were not.
Pain intensity did not
correlate with test
scores
Lorenz, Beck, and
Bromm (1997)
Visual analog scale 5 visual analog
scales
Subtle improvement in
auditory vigilance in
association with
reduced pain intensity
post treatment
Pincus, Fraser, and
Pearce (1998)
A numerical rating scale Hospital Anxiety
and Depression
(HAD) Scale
Stroop Test Elevated depression
and anxiety scores in
pain group
Radanov et al.
(1993)
010 scale Well-being Scale
Neuroticism Scale
from Freiburg
Personality
Inventory
TMT? Digit Span?
Corsi Block
Tapping?
Number
Connection Test?
PASAT?
Correlations between pain
intensity and test scores
ranged from 0 to .50.
Medication use
inuenced
performance on TMT
and PASAT
Radanov, Dvorak,
and Valach (1992)
No No PASAT? Number Connection Test Patients with UCS
were impaired on the
PASAT based on norms
and performed worse
than those with LCS
(Continued )
Chronic Pain 137
Radanov, Hirlinger,
DiStefano, and
Valach (1992)
No Freiburg
Personality
Inventory
Well-being Scale
DSM-III-R
diagnosis
PASAT
TMT
Number Connection Test Both groups of pain
patients were impaired
based on norms. Poor
performance on PASAT
was associated with
lower self-ratings of
emotional well-being
and higher nervousness
Schmand et al.
(1998)
No No WAIS Digit
Symbol
Category
Fluency
AVLT
Logical Memory
(Rivermead)
TMT
Stroop Test
Whiplash patients who
passed malingering test
performed less well
than normal controls,
but better than those
who did not pass the
malingering test and
better than moderate-
severe TBI group
Schwartz et al.
(1987)
Symptom
Checklist 90
(SCL-90)
COWA
PASAT
TMT
25% rated as possibly
or mildly impaired.
They were less likely to
be rated as impaired
than group with
suspected TBI but there
were no mean
differences on tests
Sletvold, Stiles, and
Landro (1995)
No Beck Depression
Inventory
Structured Clinical
Interview for
DSM-III-R
WAIS Digit
Symbol
PASAT
Visual 2-choice
RT
TMT
WAIS Similarities and
Block Design
Pain patients performed
similar to patients with
major depression (MD)
but worse than normal
controls. A subgroup
of pain patients with-
out history of MD
normal controls and
similar to a subgroup of
pain patients with a
history of MD and to
MD group
Taylor, Cox, and
Mailis (1996)
Verbal analog scale
The pain groups
matched on rated
pain intensity
MMPI
The pain groups
matched on level
of depression
PASAT
Consonant
Trigrams Test
Each pain group
performed below
normal levels on one of
the two tests, and
similar to one another
and to a group of
patients who had
suffered moderate to
severe TBI years
earlier. Neither pain
intensity nor depression
correlated with tests
Note. CNS =central nervous system; COWA =controlled oral word association; CVLT =California verbal learning test; ISI =interstimulus interval; MMPI =
Minnesota multiphasic personality inventory; PASAT = paced auditory serial addition test; (R)AVLT = (Rey) auditory verbal learning test; RT = reaction
time; TBI = traumatic brain injury; TMD = temporomandibular disorder; TMT = trial-making test; WAIS-(R) = Wechsler adult intelligence scale-(revised);
WMS-R = Wechsler memory scale-revised.
Schwartz et al. (1987) studied a group of chronic pain
patients without a history of head trauma who suffered
chiey fromlowback pain. Approximately 25%of the pa-
tients were rated as demonstrating possible or mild decits
on the Paced Auditory Serial Addition Test (PASAT),
Trail-Making Test, and/or Controlled Oral Word Associ-
ation Test. The patients completed a self-report inventory
that included measures of somatization, depression, and
anxiety, but it is unclear whether those patients rated as
showing possible or mild decits reported higher levels
of psychological distress. Kewman, Vaishampayan, Zald,
and Han (1991) reported a similar incidence of impair-
ment (32%) in patients with musculoskeletal pain who
had no history of diagnosed cognitive impairment or
degenerative disease. Location of pain was primarily in
the low back (33%) or in multiple sites (25%). These in-
vestigators employed a cognitive screening measure on
which most normal adults achieve nearly perfect scores.
The most common decit evidenced by the patients was
memory for four words following a 10-minute delay. A
composite score correlated with ratings of pain and rat-
ings of disability (interference with daily activities). The
study included ratings of psychological distress (depres-
sion, anxiety, irritability, andenergylevel) anda composite
measure of distress was found to correlate with a compos-
ite score from the cognitive screening measure. The au-
thors did not report the degree of the association between
rated pain and rated psychological distress, however.
Studies with Normal Control Subjects
Eccleston (1994) evaluated patients with chronic
benign pain. Approximately one-third of the patients
suffered low back pain and remaining had pain involv-
ing a variety of other single or multiple sites. Patients
with head pain and patients being treated for depressive
symptoms were excluded. Some of the patients were using
opiate-based analgesics, but regression analyses revealed
no relationship between test performance and drug sta-
tus. The pain patients were divided into groups reporting
high levels of pain intensity and those reporting lowlevels
of pain intensity. Patients reporting greater pain intensity
performed worse on an attention demanding numerical
interference task than patients reporting lower levels of
pain and normal control subjects. In the task used, sub-
jects were shown two cards, each with one to nine items,
where the item was a single digit 1 through 9. In the test
condition that showed a group effect, subjects indicated
the largest number of digits for each card pair (rather than
the value of the largest digit) on a numerical keypad and
reaction time was recorded. A measure of distress from
a short form of the McGill Pain Questionnaire was not
signicantly related to reaction time. However, this study
provided minimal opportunity to explore possible rela-
tionships between pain intensity, emotional status, and test
performance given the exclusion criteria and the absence
of data from mood scales.
Eccleston (1995) replicated the above nding in an-
other group of patients with benign pain, usually in-
volving the lower back or a limb. Patients with head pain
or severe emotional problems were excluded. Neither
medication status nor the level of anxiety or depression
were signicantly correlated with reaction time, although
the latter negative nding should be interpreted in light of
the exclusion criteria and the fact that pain patients and
control subjects exhibited a similar frequency of mood
disturbance. A second, more demanding attentional test
was also employed. Subjects were required to switch un-
cued(inanalternatingsequence) betweenrespondingwith
the value of the largest digit for each card pair and re-
sponding with the largest number of digits for each card
pair. Again, patients reporting greater pain intensity were
impaired on the task. In a subsequent study of similar
chronic pain patients (Eccleston, Crombez, Aldrich, and
Stannard, 1997), the nonswitching version of the atten-
tional test was used, and subjects indicated the position
of the card with the larger digit value or the position
of the card with the larger number of digits by press-
ing a computer key marked left or right. The vari-
able of interest was the difference in reaction time in
processing the nondominant information (number of dig-
its) and in processing the dominant information (value
of the digits). The majority of patients had back pain
and the others had widespread muscle pain, limb pain,
or diffuse pain (excluding head or cancer-related pain).
Only those patients reporting both high somatic aware-
ness (greater frequency and/or breadth of diffuse somatic
complaints) and high pain intensity showed disruption of
attention. This group also reported the greatest affective
distress (depression and anxiety), although the relation-
ship between level of psychological distress and test per-
formance was not examined. No effect of medication was
shown.
Several studies have assessed patients with bromya-
lgia. Importantly, bromyalgia is characterized by chronic
fatigue and sleep disturbance, as well as pain, and patients
often suffer from signicant mood disturbance. In a pre-
liminary study, Grace, Berg, and Nielson (1995) found
evidence of mild memory impairment in patients with
bromyalgia relative to a group of normal control sub-
jects. The study did not include pain ratings or measures
of mood, although the authors did assess subjective sleep
quality, which was poorer in the patients than in the con-
trol subjects. In a larger followup study (Grace, Nielson,
Hopkins, and Berg, 1999) bromyalgia patients referred
to a treatment programperformed worse than normal con-
trol subjects on some of the measures of immediate and
delayed memory (WMS-R General Memory and Delayed
Recall Indices) and attention/information processing
speed (PASAT). The pattern of decits was interpreted as
indicating a primary decit in attention. Pain severity and
trait anxiety, but not depression or subjective sleep qual-
ity (which was worse in pain patients) correlated with test
performance. Partial correlations suggested that anxiety
was more related to performance decrements than pain
severity. Pain patients also tended to overestimate their
cognitive problems on a self-rating scale. Medication use
was not related to test performance.
Chronic Pain 139
Sletvold, Stiles, and Landro (1995) found decits on
tests requiringattention, rapidinformationprocessing, and
psychomotor speed in patients with bromyalgia. Patients
with bromyalgia performed similar to patients with ma-
jor depression, but worse than normal control subjects
on WAIS Digit Symbol and the PASAT, and on a visual
2-choice reaction time test. There were no group differ-
ences on the Trail-Making Test. This study included no
ratings of pain, but the affective state of patients was ascer-
tained using the Beck Depression Inventory and the Struc-
tured Clinical Interview for DSM-III-R. The bromyalgia
group reported an average depression score in the mild
range and evidenced a high frequency of anxiety disorders
(e.g., 64% with a generalized anxiety disorder) and so-
matoform disorder. The decits in the bromyalgia group
were not simply attributable to comorbid psychiatric dis-
order, however, as a subgroup of patients without a life-
time history of major depression (and lower frequency
of anxiety disorders) performed worse than the control
group on Digit Symbol and the PASAT. The subgroup
of bromyalgia patients without a history of major de-
pression performed similar to bromyalgia patients with
a history of major depression and to the depressed group.
In contrast, in a study using the same subject sam-
ples (Landro, Stiles, and Sletvold, 1997) only those -
bromyalgia patients who had a lifetime history of major
depression showed memory impairment relative to normal
controls. The total group of pain patients performed sim-
ilar to patients with major depression, and were impaired
on the Randt Memory Test, the Code Memory Test (re-
call of letter-number associations from a translation list),
and letter uency. Impairments were not demonstrated on
Digit Span or Kimura Recurring Figures Recognition Test.
Neither rated pain intensity nor fatigue level correlated
with memory tests that differentiated the groups.
Cote and Moldofsky (1997) studied sleep and cog-
nitive performance on a computerized battery of tests in
bromyalgia patients. Relative to normal control subjects,
the pain patients exhibited more stage 1 sleep on polysom-
nography, and reported more fatigue, more sleepiness,
more intense pain, more negative mood including depres-
sion, and a perception of lower accuracy of performance.
Patients had a lower composite score and response rate
on a simulated multitask ofce procedure involving short-
termmemory for a list of letters, addition problems, visual
monitoring of a moving pointer, and auditory attention to a
low versus high frequency tone. They were also impaired
for speed, but not accuracy, of serial addition/subtraction
and grammatical reasoning, although this was reduced to a
marginally nonsignicant level when education was used
as a covariate in the analyses. No impairments were shown
on tests of simple reaction time or short-term memory for
patterns of squares. Stage 1 sleep covaried with rate of
response on the simulated task, and somatic items from
the Beck Depression Inventory covaried with performance
across all cognitive tests, as well as with ratings of pain
and fatigue. The authors suggest that sleepiness and perva-
sive fatigue associated with persistent myalgia most likely
account for impaired cognitive performance.
Schmand et al. (1998) studied chronic whiplash pa-
tients (mean post-injury interval 2 years) either as part of a
litigation procedure, or as part of an evaluation at an out-
patient clinic. Patients with head injury or loss of con-
sciousness were excluded. Whiplash patients without ev-
idence of underperformance on a test designed to detect
malingering performed worse than normal control sub-
jects on some measures of attention and psychomotor
speed (Symbol Digit Substitution) but not others (Trail-
Making, Stroop Test). They also performed less well on
tests of verbal memory (Auditory Verbal Learning Test,
Logical Memory) and verbal uency. Potential medication
effects were not explored and ratings of pain intensity and
measures of mood disturbance were not included. One
other study did not show the Stroop Test to be sensitive
to the effects of chronic pain. Pincus, Fraser, and Pearce
(1998) found no difference between chronic pain patients
from a pain clinic or a support group, and normal control
subjects on the standard Stroop interference condition.
Depression and anxiety were higher in the pain group, but
the mean pain intensity rating at the time of testing was
modest (e.g., 30 on a scale of 1101 in experiment one).
Studies without Normal Control Subjects
Grigsby, Rosenberg, and Busenbark (1995) studied
a group of chronic pain patients without a history of head
injury, although 8 of 19 had suffered whiplash injuries.
Pain was primarily myofascial and localized to the head,
neck, or backregion. The painpatients displayeddecits in
simple and choice reaction time relative to normative data
and a group of patients who had suffered a mild to moder-
ate brain injury. The pain group had milder difculties on
tests of simple motor speed (nger-tapping) and motor co-
ordination (nger-to-nose testing), and no impairment on
tests of short-term visual memory (immediate recall of a
sequential pattern of lights and visual numerical memory).
However, no assessment was made of mood or emotional
distress.
Taylor, Cox, and Mailis (1996) compared chronic
pain patients without a history of trauma or CNS disorder
to patients who had suffered a whiplash injury (without
loss of consciousness) and to patients who had suffered
a TBI of at least moderate severity years earlier. Pain
symptoms were primarily regional, involving the back or
limbs. The chronic pain group without a history of trauma
and the whiplash group were matched on rated pain in-
tensity and level of depression, but only the latter group
had been referred for a medical-legal evaluation. All three
groups showed similarly low normal to mildly impaired
performance on the PASAT and on the Consonant Tri-
grams Test. In the latter test, subjects recalled a list of
consonant triads after intervals ranging from018 seconds
lled by distracting activity. Both the pain group without
trauma and the whiplash group reported symptoms of de-
pression (MMPI-2 scale 2 T scores = 76 and 74, respec-
tively). Neither pain intensity nor MMPI scale 2 elevations
correlated with cognitive test performance, although the
authors point out that there was a narrow range of scores
on both of these measures. Relationships between pain rat-
ings and depressive symptomatology were not reported.
Radanov, Hirlinger, DiStefano, and Valach (1992)
compared patients with a cervical spine syndrome caused
by rheumatism (Barrelieou Syndrome) and patients with
whiplash injuries who had not suffered head trauma or a
loss of consciousness. Relative to normative values both
groups showed impaired performance on the PASAT.
Patients with rheumatism were also administered Trail-
Making Part B and had low performance relative to
normative data. No formal ratings of pain intensity were
obtained. Twenty-one percent of patients with rheumatism
were diagnosed with dysthymia while there was a higher
incidence of adjustment disorder (52%) and a higher level
of self-reported nervousness in the patients who had suf-
fered a whiplash injury. Poor performance on the PASAT
was associated with lower self-ratings of emotional well-
beinginbothgroups andwithhigher levels of self-reported
nervousness in the whiplash group.
In contrast to the studies cited above, Bell, Primeau,
Sweet, and Loand (1999) found no evidence of impair-
ment in chronic pain patients. Measures included tests
of visual-perceptual ability (WAIS-R Block Design,
WMS-R Visual Reproduction I), memory (3 subtests
fromWMS-R), andattention/psychomotor speed(PASAT,
Stroop Test, Trail-Making Test). The chronic pain patients
were nearly all from a specialty clinic, and the majority
(65%) suffered fromback pain. Depression level fell in the
mild range. Fifteen percent of the pain group performed
at a low level expected in only about 5% of a normal
control sample; this difference in frequency of low scores
between patients and the normative standard was not sta-
tistically signicant. Because comparisons to normative
data were not reported for individual tests, it is unclear
whether the PASAT (which in this study included only the
rst two trials) or any other single measure tended to be
sensitive to effects of chronic pain. Perhaps noteworthy,
pain intensity was relatively modest (mean rating of 2.6
on a 7-point scale).
Kaplan, Meadows, Vincent, Logigian, and Steere
(1992) found that bromyalgia patients and depressed pa-
tients with similar elevations on scale 2 of the MMPI had
no differences on memory tests, but both groups tended to
perform less well than patients with Lyme encephalopa-
thy. Because the study did not include a normal control
group or contrast scores to normative data, it is unclear
whether the pain patients exhibited any impairment.
The impact of pain on cognitive functioning has also
been inferred from treatment studies. Lorenz, Beck, and
Bromm (1997) studied a small group of patients with
chronic pain associated with osteoporosis, Crohns dis-
ease, neuropathy, or low back problems. They found a
subtle improvement in auditory vigilance as assessed by
reaction time and P300 of the event-related potential in
association with a signicant reduction in pain intensity
ratings following sustained-release morphine treatment.
Patients also reported reduced tension and depression,
but relationships between mood and cognition were not
explored.
Effects of Head/NeckPainandAssociatedSymptoms
Some studies suggest increased vulnerability to cog-
nitive impairment in patients with pain and other symp-
toms referable to upper cervical regions, as with many
whiplash-type injuries. Radanov, Dvorak, and Valach
(1992) studied patients with whiplash injuries who either
had symptoms referable to an upper cervical syndrome
(approximately 40% of whom reported an impairment of
consciousness at injury) or symptoms referable to a lower
cervical syndrome. Relative to normative values, only
those patients with the upper cervical syndrome were im-
paired on the PASAT. Because there were no ratings of
pain intensity, it is difcult to interpret the negative nding
in those patients with a lower cervical syndrome. No mea-
sures of emotional status were reported. Goldberg et al.
(1996) contrasted patients whose temporomandibular dis-
order (TMD) followed a cervical whiplash injury (without
loss of consciousness) and those whose TMD was idio-
pathic. Posttraumatic TMDpatients performed worse than
idiopathic TMD patients on tests of simple and choice re-
action time, verbal learning (California Verbal Learning
Test), and short-term memory under interference condi-
tions (Consonant Trigrams). The groups did not differ in
retention of a word list over a delay interval. Relative to
normative values, the idiopathic TMD patients performed
normally on Consonant Trigrams, but showed slowed re-
action times. The prevalence of depression based on the
Chronic Pain 141
Symptom Checklist-90 Revised (SCL-90R) was close to
50% for the total sample and comparable across the two
groups, but the relationship between emotional status and
cognitive performance was not explored directly.
The apparently higher incidence of cognitive impair-
ment in patients with pain referable to upper cervical re-
gions following whiplash injury may be because of any
of several factors. Goldberg et al. (1996) remarked on
the potential similarities between posttraumatic TMD pa-
tients and mild TBI patients. Their posttraumatic TMD
patients were symptomatic for at least 6 months follow-
ing injuries that did not involve loss of consciousness. It
seems unlikely that brain injury would explain group ef-
fects at long postinjury intervals in light of epidemiologic
studies of recovery frommild TBI (Dikmen, McLean, and
Temkin, 1986; Levin et al., 1987). The attentional impair-
ments demonstrated within days of common whiplash in-
jury and subtle sequelae in a small subgroup who remain
symptomatic for longer periods of time have not been at-
tributed to brain injury in other studies (DiStefano and
Radanov, 1995; Radanov et al., 1993). In the latter studies,
patients with head injury or alteration of consciousness,
including posttraumatic amnesia, were excluded.
The study by Schmand et al. (1998) highlights the po-
tential confound of malingering or more subtle forms of
suboptimal performance in whiplash patients. In a nonrep-
resentative sample in which only 12 of 108 patients were
not involved in litigation, a damage claim, or a workmens
compensation claim, about 60% of those referred as part
of a litigation procedure and about 30% of those referred
as part of a clinic evaluation scored below the cut off on
the Amsterdam short-term memory test for the detection
of malingering. Those whiplash patients scoring belowthe
cutoff performed about as poorly as patients with a history
of serious head injury (mean GlasgowComa Scale =9.3).
Of particular relevance to this review, another pos-
sible explanation for worse cognitive performance in
whiplash-injury patients with symptoms referable to the
upper cervical region is that the pain experienced is some-
times more severe or widespread than for other patients.
Goldberg et al. (1996) found that signs of tenderness
to palpation on the basis of the evoked reaction were
more severe and widespread in the posttraumatic TMD
patients than the idiopathic TMD patients. None of the
patients with idiopathic TMD, but 38% of the patients
withposttraumatic TMDdemonstratedpainreactions with
palpation of the external masseter, temporalis, and stern-
ocleidomastoid muscles. In a study of whiplash patients
without TBI recruited from primary care physicians
(Radanov et al., 1993) mean performance on attentional
tests including the PASAT fell within the normal range at
6 months postinjury, except for Trail-Making Part B in a
subgroup of symptomatic patients. Correlations between
neck pain/headache intensity and cognitive test scores at
the 6-month follow-up ranged from 0 to 0.50 in the symp-
tomatic patients (correlations were not provided for indi-
vidual tests). The correlation between pain intensity and
test scores was not attributable to litigation status, but was
potentially confounded by individual variations in medi-
cation use, which had been shown to affect performance
on the Trail-Making Test and the PASAT.
In a 2-year follow-up study involving the same sam-
ple, DiStefano and Radanov (1995) contrasted the perfor-
mance of a subgroup reporting persistent injury-related
complaints (18% of sample) and a subgroup of demo-
graphicallymatchedpatients selectedfromthose whowere
asymptomatic. Performance on attentional tests was nor-
mal in the symptomatic group except for marginally im-
paired scores on the PASAT and slower times on Trail-
Making Part B at 2 years postinjury than at baseline.
Symptomatic patients performed signicantly worse on
the PASAT than the demographically matched asymp-
tomatic patients at both 6-month and 2-year follow-up
intervals. At 2-years postinjury, the symptomatic patients
reported a frequency of neck pain similar to that of asymp-
tomatic patients at baseline (i.e., days within injury) and a
frequency of headache higher than that of asymptomatic
patients at baseline (86% vs. 52%). Rated pain intensity
was higher inthe symptomatic groupat follow-upintervals
than that of asymptomatic patients at baseline, and pain
intensity was shown to signicantly covary with PASAT
scores. Medication use covaried with PASAT scores at
6 months.
The extent of discomfort from symptoms often asso-
ciated with pain, such as fatigue and mood disturbance,
may be greater in those whiplash-injury patients demon-
strating relatively more cognitive impairment. For exam-
ple, Radanov, Dvorak et al. (1992) observed more stress
symptoms during testing in those patients with an upper
cervical syndrome relative to those with a lower cervi-
cal syndrome. Goldberg et al. (1996) note that posttrau-
matic TMD patients tend to suffer from a higher degree
of symptoms suggestive of affective disorder, includ-
ing sleep disturbance, decreased energy level, and mood
swings. In their study, reaction times fromrepeat testing at
the end of the session were unchanged in patients with id-
iopathic TMD but decreased signicantly in patients with
posttraumatic TMD, suggesting that fatigue was a factor
contributingtothe decits inthe latter group. Inthe follow-
up study of whiplash patients by DiStefano and Radanov
(1995), the patients who remained symptomatic and ev-
idenced subtle attentional impairments at 6 months and
2 years postinjury also reported a higher incidence of such
symptoms as sleep disturbance, fatigue, and anxiety; the
incidence of these symptoms was higher at 2 years than
it was in the asymptomatic group at baseline (i.e., within
days of injury). Emotional well-being was rated lower by
the patient group impaired at follow-up intervals, and the
level of subjective cognitive impairment in daily activities
actually increased over consecutive follow-up intervals.
Headache pain may be uniquely disruptive. For ex-
ample, in the study by Radanov, Dvorak et al. (1992),
the group that showed impairment on the PASAT reported
twice the frequency of headache as the group that did
not (80% vs. 40%). DiStefano and Radanov (1995) found
that headache intensity covaried signicantly with PASAT
performance at long-term follow-up in whiplash patients.
In the study by Radanov, Hirlinger et al. (1992) patients
with whiplash injuries and Barr e-Lieou syndrome showed
equally impaired performance on the PASAT. However,
patients from both groups who suffered exclusively from
brachialgia scored in the normal range, suggesting that
headache was a crucial factor in contributing to attentional
problems in the whiplash patients. In a review conducted
by Nicholson (1998), seven of nine studies examining
headache without TBI noted at least some impairment
relative to controls, although in some cases this was quite
modest. Interestingly, Radanov et al. (1992) remark that
during testing, patients with an upper cervical syndrome
complained of developing headaches accompanied by au-
tonomic reactions (e.g., sweating, facial ush, increased
heart rate). Other research has shown a relatively high inci-
dence of anxiety, depression, stress, and somatoform dis-
order in patients with tension-type headache (e.g., Puca,
Prudenzano, Savarese, Genco, andSpeechio, 1997), which
might be a factor contributing to the disruptive impact
on behavior. On the other hand, Lake, Branca, Lutz, and
Saper (1999) recently reported scores that were gener-
ally within normal limits for a group of 125 chronic post-
traumatic headache patients being followed at a treatment
center an average of 32 months after mild head/neck in-
jury; the test battery emphasized memory, but included a
number of tasks requiring attention, psychomotor speed,
and mental exibility (e.g., Controlled Oral Word Associ-
ation, PASAT, Stroop Test, Symbol Digit Modalities Test,
and Trail-Making).
Other symptoms associated with a cervicoence-
phalic syndrome may reduce mental efciency. In the
study by Radanov, Dvorak et al. (1992) most patients
showing impairment on the PASAT had a distinct symp-
tomcomplex characterized by a higher incidence of dizzi-
ness, blurred vision, and disturbed adaptation to light as
well as more frequent headache. In the study of TMD
patients cited earlier (Goldberg et al., 1996), the post-
traumatic group performing worse on neuropsychological
tests reported a signicantly higher number of somatic
complaints on the SCL-90 modied for use with TBI
populations. Decits in attention and memory have been
demonstratedinwhiplashpatients selectedfor chronic dis-
turbances inthe posture control systemas demonstratedon
The Smooth Pursuit Neck Torsion Test (Gimse, Bjorgen,
Tjell, Tyssedal, and Bo, 1997). The patients had decits
on the Rey Auditory Verbal Learning Test (learning and
retention) and on the PASAT with a prolonged interstim-
ulus interval. Other attentional tests (PASAT at a standard
interstimulus interval and Trail-Making) showed no im-
pairment. In this study, no assessments were made of pain
intensity or mood disturbance, but medication effects were
ruled out. Although some patients were in litigation or
awaiting compensation from an insurance company, ma-
lingering seemed unlikely given the correspondence be-
tween neuropsychological data and measures not so easily
controlled voluntarily. The authors speculate that distur-
bances in automatized functions, such as neck propriocep-
tive input to the postural control systemand the associated
inuence on the reticular activating system, may affect
attention.
NONCLINICAL PAIN POPULATIONS
In contrast to the studies reviewed thus far, there is no
compelling evidence of an association between pain and
psychometric test performance in nonclinical populations,
at least for pain not involving the cervical region. Astrand
(1987) divided male employees in the pulp and paper in-
dustry into groups with versus without back pain on the
basis of their response to a single yes/no question and into
groups with versus without back abnormality on the ba-
sis of physical examination. Cognitive measures included
a synonyms test, an arithmetic test, and an instruction
test that purportedly assessed general intelligence. There
were no associations between cognitive performance and
back pain or back abnormalities beyond what could be at-
tributed to group differences in education and social class.
Interestingly, a measure of neuroticismderived fromques-
tions on a medical index showed signicant associations
with both signs and symptoms of back problems, although
no examination of possible correlations with test perfor-
mance was reported.
Although limited data are available, the lack of evi-
dence for cognitive impairment in nonclinical pain popu-
lations is perhaps not surprising. Pain that does not lead
to treatment seeking would presumably tend to be less
bothersome and disruptive of daily life and work activi-
ties, and hence less likely to impact cognitive functioning.
That is, such pain presumably is associated with a differ-
ent perception, tolerance, or attitude toward the symptoms
(Ziegler and Paolo, 1995).
Chronic Pain 143
PATIENTS WITH CNS DISORDERS
AND BRAIN INJURY
We have reviewed studies of chronic pain patients,
including those who have suffered whiplash-type injuries
without head trauma or loss of consciousness. The pos-
itive ndings in patients with chronic pain syndromes
does not imply that there is necessarily the same rela-
tionship between pain symptoms and neuropsychologi-
cal performance in patients whose CNS disorders or in-
juries are sufcient to produce persistent neurological and
neuroimaging abnormalities; associations between pain
and cognitive dysfunction may be attenuated by the over-
riding impact of structural brain damage. For example,
disorders have been described in which pain is a com-
mon symptom but no relationship to neuropsychological
performance was found, e.g., eosinophilia myalgia syn-
drome (Armstrong, Lewis, DEsposito, and Freundlich,
1997; Pollina, Kaufman, Masur, and Krupp, 1998).
Although a review of the relevant studies is beyond
the scope of this paper, there certainly can be an interac-
tion of brain injury and chronic pain. For example, Denys,
Azouvi, Denormandi, and Samuel (1996) described a case
in which performance on neuropsychological tests paral-
leled improvement of pain problems in a severe closed
head injured patient, and as described earlier, Vernon-
Wilkinson and Tuokko (1993) found that TBI patients
with pain did worse on neuropsychological tests thanthose
without pain. Several investigators have found consider-
able overlap in the symptoms of chronic pain and mild
traumatic brain injury, leading the authors to conclude
not only that chronic pain complicates the symptom pic-
ture in TBI but that resolution of the postconcussive syn-
drome and successful adaptation to residual sequelae may
frequently rely on success in coping with posttraumatic
headache and/or other pain symptomatology (e.g., Andary
et al., 1997; Martelli et al., 1999; Miller, 1990). Although
most cases of mild TBI resolve without persistent postcon-
cussive sequelae, a small percentage do experience persis-
tent symptomalogy. In these cases, headache or other pain
problems may contribute to or explain persistent cognitive
complaints.
NEUROPHYSIOLOGICAL CORRELATES
OF CHRONIC PAIN
Over the last several decades, a variety of theories
have been proposed to explain the neurophysiologic cor-
relates of pain, both acute and chronic. Although there are
no universally accepted hypotheses, the gate control the-
ory, proposed by Melzack and Wall (1965) has probably
received the most acknowledgment. In this theory, dorsal
horn neuron mechanisms in the spinal cord modulate input
to the brain through the substantia gelatinosa and spinal
cord transmission cells (so-called T cells). Activation of
large A-beta bers inhibits transmission to the T-cells, thus
closing the gate. Activation of small A-delta and Cbers
increases transmission through these cells, thereby open-
ing the gate. Other mechanisms that are involved in pain
mediation include supraspinal inputs that activate large di-
ameter bers and involve certain cognitive processes, thus
constituting a mind-body interaction. More recently,
Melzack has suggested that although the basic conceptual
model of gate control may be correct, the gate system is
much more complicated than initially thought (Melzack,
1996; Melzack, 1999). Melzack has proposed the concept
of a Neuromatrix nervous system that is composed of a
widely distributed neural network consisting of thalamo-
cortical and cortico-limbic links that serve as the anatomi-
cal substrate of the body-self involved in processing pain.
It is postulated that the distribution of the Neuromatrix
is initially determined genetically but is later molded by
sensory inputs and includes a neurosignature, based in the
parietal lobe, which signals sensations in different parts
of the body.
Given the frequent correlation of chronic head and
neck pain with cognitive impairment, it would seem only
reasonable to pursue neurophysiologic explanations that
link these two phenomena via some common factor or set
of factors. One of the more prominent theories suggests
that the pain center of the cranium is in the spinal nucleus
of the trigeminal nerve, which is continuous with the pain
center in the upper cervical spine. Accordingly, trigeminal
afferent bers synapse on the same second order neurons
as do the afferents from levels C1 to C3 (afferent conver-
gence). Two of the three types of dorsal motor neurons
are involved in pain transmission; specically, nocicep-
tor specic (NS) cells and wide dynamic range (WDR)
cells. Small diameter nociceptive afferents contain excita-
tory neurotransmitters including glutamate and aspartate
as well as neuropeptides such as substance P and calci-
tonin gene-related peptide (CGRP). The major transmit-
ter involved in the small-diameter pain bers appears to
be glutamate. Release of glutamate activates N-methyl-
D-aspartate (NMDA) as well as non-NMDA receptors.
This results in additional chemical alterations including
an inux of intracellular calcium that may activate several
signal transduction systems including phosphokinase C
and facilitation of nitric oxide production (Coderre, Katz,
Vaccarino, and Melzack, 1993; Woolf and Thompson,
1991).
Importantly, in a review of several studies, Martelli
et al. (1999) found consistent evidence of regional cerebral
blood ow abnormalities in persons with chronic pain
(i.e., Di Piero et al., 1991; Mountz, Bradley, and Alarc on,
1998; Mountz et al., 1995; Sendrowski, Buker, and Gee,
1997). Abnormalities have been reported for bromyal-
gia, high cervical cordotomy, and other muscular and non-
neurologic disorders. These ndings have been interpreted
as offering support to the idea that chronic pain exerts
a potentially disruptive physiological effect on cerebral
functioning in general and therefore in theory may inter-
fere with cognitive functioning. Neuroimaging studies and
other research indicates that medial thalamic nuclei, the
anterior and mid-cingulate, and perhaps other structures
mediate the affective-motivational component of pain and
seem to play a role in response selection and attentional
mechanisms (Treede, Kenshalo, Gracely, and Jones, 1999;
Vogt, Derbyshire, and Jones, 1996). However, whether the
changes noted on functional imaging studies represent a
type of central neuroplastic effect of chronic pain remains
to be claried.
Although the exact nature of how pain affects differ-
ent aspects of cognitive functioning is unknown, there are
a number of possibilities that can be hypothesized. The
direct effect of chronic pain-related central neurochemi-
cal changes may impact cognition through production of
substances that are functionally inhibitory to various
aspects of information processing, affecting attention and
memory. Secondaryeffects of chronic painrelatedtostress
and the associated increase in systemic, and more impor-
tantly, central glucocorticoid production likely also play a
role in impairment of acquisition or consolidation of mem-
ories, and secondarily, retrieval (deQuervin, Roozendaal,
and McGraugh, 1998). As of yet, there is not a good un-
derstanding of what cortical and subcortical neuroplastic
events occur in association with acute or chronic pain. It is
likely that such events impact other aspects of brain func-
tion including cognition, potentially through a mechanism
such as reverse diaschesis or as yet other unexplained
inhibitory processes.
Several investigators have theorized that processing
of signicant or more severe pain requires conscious cen-
tral attentional control and that subjects with lowpain may
be able to divert attention away from pain to the task at
hand, achieving a degree of psychoanalgesia (Eccleston,
1994). Eccleston (1994) and Grigsby et al. (1995) have
conceptualized pain as an attention-demanding percep-
tual stimulus, and attention as a nite and unitary re-
source. Pain competes for limited attentional resources
and thereby affects the performance of tasks that involve
the processing and integrating of other information. Pain
is more likely to disrupt performance of a demanding task
because of the greater aggregate drain on attentional re-
sources. Eccleston and Crombez (1999) further developed
a theory dealing with the interruptive function of pain rel-
ative to attentional processing. They theorized that pain
interruption of attention was mediated through both pain-
related characteristics (e.g., the threat value of pain) and
environmental demands (e.g., emotional arousal). Pain is
therefore selected for action from within complex affec-
tive and motivational environments to urge escape. Other
investigators have posited that attentional biases in chronic
pain states are best explained by concurrent mood states
of anxiety and depression as opposed to pain itself (Pincus
et al., 1998).
VARIABLES MEDIATING THE EFFECTS
OF CHRONIC PAIN AND DIRECTIONS
FOR FUTURE RESEARCH
Pain variables that have been related to cognitive
impairment include intensity and location (e.g., presence
of headache or cervical muscle involvement). An inverse
relationship between test performance and pain inten-
sity would seem consistent with the type of mechanism
proposed by Eccleston (1994), Eccleston and Crombez
(1999), and Grigsby et al. (1995), as discussed above. It
also seems plausible within the context of this explanation
that head/neck pain could have a particularly detrimental
effect on information processing capacity.
There is evidence, however, that effects of pain on
cognitive functioning are not mediated in a simple fashion
by factors such as its current intensity and location. For ex-
ample, at least two studies of patients with mild head/neck
injury (Lake et al., 1999; Tsushima and Newbill, 1996)
have failed to demonstrate detrimental effects on perfor-
mance as a function of the presence or intensity of head-
ache reported at the time of testing, although a trend
toward weaker concentration and immediate memory in
patients with severe headache was observed in one of them
(Tsushima and Newbill, 1996). It appears that concomi-
tants of chronic pain and not just immediate pain sensation
account for the effects on cognition. Grace et al. (1999)
showed that pain intensity and mood disturbance covaried
in their sample and when the effect of mood was partialled
out, pain intensity no longer correlated with test perfor-
mance. Kewman et al. (1991) also found that the correla-
tion between pain ratings and cognitive performance was
reduced to a nonsignicant level when a composite score
of psychological distress was used as a covariate. The
study of chronic pain patients by Eccleston et al. (1997)
showed that the detrimental effect of pain on an attention-
demanding task could be accounted for by increased so-
matic awareness, operationalized as responses to a ques-
tionnaire assessing the frequency and breadth of diffuse
Chronic Pain 145
somatic complaints. Increasedsomatic awareness was also
associated with higher levels of depression and anxiety.
The authors speculate that a somatic focus and emotional
factors increase the disruptive inuence of pain on atten-
tion by facilitating access of pain into awareness. Other
studies of pain patients have found associations between
the level of somatic complaints and cognitive performance
(Cote and Moldofsky, 1997; Kaplan et al., 1992).
Studies to date have not examined whether such vari-
ables as the degree of suffering and ongoing lifestyle
disruption experienced by chronic pain patients mediate
nonspecic adverse effects on cognitive functioning. Nor
have studies addressed whether maladaptive evaluative
thoughts about chronic pain adversely affect attentional
resources and cognitive performance. The trend toward
worse neuropsychological performance in posttraumatic
pain patients (without evidence of brain injury) relative to
other pain patients would also be consistent with a role for
factors other than pain intensity and location. In the case of
trauma patients, it is interesting to speculate whether the
emotional reactions or the attributions associated with the
victim role may partly mediate behavioral and cognitive
disturbance.
The weaker association between pain and cognitive
performance in nonclinical populations also suggests that
selection factors are relevant. A comparison between per-
sons who seek medical assistance for headache pain and
nonpatient volunteers who have similar headache fre-
quency and usual pain severity revealed differences in
personality traits suggesting that those who seek help have
a different perception, tolerance, or attitude toward pain
(Zeigler and Paolo, 1995). Group differences on the per-
sonality measure used in this study (MMPI-2) were not
attributable to the only pain variable that distinguished
the groups (intensity of the most severe headache).
The studies reviewed here suggest associations be-
tween neuropsychological impairment and symptoms or
other features often associated with chronic pain such
as mood change/emotional distress, increased somatic
awareness, sleep disturbance, fatigue, and perceived in-
terference with daily activity. The presence of symptoms
such as dizziness and visual disturbance of a cervicoen-
cephalic syndrome may also be associated with greater
cognitive impairment. Studies reviewed here, as well as
other research with pain patients, have established that
emotional distress frequently accompanies chronic pain.
Depression in chronic pain patients can frequently be at-
tributed to a disruption in preferred role functions, life-
styles activities, sources of satisfaction and reinforcement,
and ones sense of identity and self esteem (Martelli,
Zasler, Mancini, and MacMillan, 1999). Cognitive com-
plaints in chronic pain patients are more closely related
to measures of emotional distress than to pain variables
like rated intensity, and are also associated with interfer-
ence of everyday activities or at least a reduced desire for
activities (Dufton, 1989; Jamison, Sbrocco, and Parris,
1988). Schnurr and MacDonald (1995) found that self-
reported cognitive problems and associated mood distur-
bance in chronic pain patients exceeded those of general
medical-dental and psychotherapy patient groups without
pain-related problems, and that partialing out the effect of
mood signicantly reduced the group differences in cog-
nitive complaints. Surveys and sleep laboratory studies
indicate that sleep disturbance and associated symptoms
such as fatigue are also common in chronic pain patients
(see Morin, Gibson, and Wade, 1998). In the latter study,
more than 90% of the patients referred to an outpatient
pain clinic reported that the onset of sleep disturbance co-
incided with, or followed, the onset of pain. Rated pain in-
tensity was greater in poor sleepers. Poor sleep in chronic
pain patients has, in turn, been associated with emotional
distress (e.g., Atkinson, Ancoli-Israel, Slater, Garn, and
Gillin,1988), although the relationship between pain and
sleep disturbance is not necessarily mediated by mood
disturbance (Morin et al., 1998). An interdependent, re-
ciprocal relationship appears to exist, wherein pain can
contribute to sleep disturbance and depression, sleep dis-
turbance can increase pain symptomatology and mood
disturbance, and depression can contribute to sleep distur-
bance and the affective component of the pain experience.
Research to date has not explored in a comprehen-
sive manner the interrelationships among such variables
as pain intensity, pain location, sleep disturbance, fatigue,
tendencies toward somatization and/or somatic vigilance,
and emotional state. It is thus unclear to what extent these
different factors mediate the inuence of pain on neu-
ropsychological performance or uniquely contribute to
subjective complaints or objective signs of impairment in
chronic pain populations. Importantly, some of the condi-
tions and symptoms associated with chronic pain, such as
depression and sleep disturbance, are known to produce
neuropsychological decits. For example, in a recent meta
analysis using stringent methodological and sample selec-
tion criteria, Veill (1997) found that major depression is
associated with impairment similar in prole to that seen
in brain injury. Even more signicant decits have been
reported for depressed elderly (e.g., King, Cox, Lyness,
and Caine, 1995). Similarly, a recent meta analysis found
that partial sleep deprivation impairs cognitive and motor
performance (Pilcher and Huffcutt, 1996). Clearly, multi-
variate regression models using independent variables of
the type identied in this review would provide valuable
information about which factors uniquely inuence neu-
ropsychological functioning in chronic pain patients.
Future studies should assess the sensory, affective,
cognitive-evaluative, and behavioral dimensions of pain
and their relationships to both subjective complaints and
neuropsychological test performance. Models of pain pro-
cessing often distinguish several stages (Harkins, Price,
and Braith, 1989; Loeser, 1982; Price, 1988; Wade,
Dougherty, Hart, Rai, and Price, 1992). The rst stage,
referring to a sensory dimension, is commonly assessed by
ratings of pain intensity. A second stage, referring to the
immediate affective response, can be measured by ratings
of pain unpleasantness. A third stage of pain processing
has been related to the meaning and implications of pain
for the individual. This stage of processing is thus often as-
sociated with emotional suffering, and can be assessed by
measuring pain-related emotional states (e.g., depression,
anxiety, frustration) and beliefs (e.g., perceived ability to
endure or reduce pain). Various methods can be used to
assess a fourth stage, referring to illness behavior (e.g.,
lifestyle interference, pain behaviors manifested at home
and during clinical interview).
Studies of cognitive functioning in patients with
chronic pain have focused primarily on ratings of pain in-
tensity. Theoretically, later stages of painprocessingwould
seem likely to mediate effects on cognitive functioning.
Sensory-discriminative and affective-motivational com-
ponents of pain appear to be processed in parallel by dif-
ferent parts of the nociceptive system(Treede et al., 1999),
and as noted earlier, for example, thalamic and cingulate
regions that appear to mediate the affective-motivational
component seem to play a role in response selection and
attentional mechanisms. Studies cited in this review that
examined multiple variables simultaneously tend to sup-
port the proposition that later stages of pain processing
play a prominent role in mediating the disruptive inu-
ence of pain on cognition. Examples of identied factors
that relate to later stages of pain processing include emo-
tional state, somatic vigilance, and perceived interference
with daily activities. To the extent that later stages of pain
processing mediate behavioral reactions, future research
should include an assessment of personality variables,
such as trait neuroticism, to help understand the impact
of pain on subjective complaints and neuropsychological
test performance. Theoretical schemes of pain dimensions
should also be applied to treatment outcome studies. Pre-
and posttreatment measurement of cognitive functions and
the multiple dimensions of pain would also advance our
understanding of the nature of the relationship between
chronic pain and neuropsychological functioning.
CLINICAL IMPLICATIONS
A discussion of clinical approaches to pain assess-
ment is beyond the scope of this review, but research
ndings have several important implications for the neu-
ropsychological evaluation of patients who have chronic
pain as one of their presenting complaints. It is important
to recognize that chronic pain and its concomitants repre-
sent a source of performance variance and that caution is
warranted in interpreting decrements in test performance
as signs of neurologic sequelae of brain disease or injury
in patients with chronic pain. In cases where pain and re-
lated symptomatology have not received specic and/or
appropriate treatment focus, considerationshouldbe given
to postponing neuropsychological assessment until more
aggressive medical and behavioral efforts aimed at reduc-
ing pain and associated symptoms have been instituted.
Especially in situations where adequate pain treatment ef-
forts have not been made, consideration should be given
to alterations in the testing situation to ensure optimal
comfort. Efforts to ensure a comfortable sitting position
and optimized ergonomics, frequent breaks, allowance for
standing or changing position, instruction to bring and use
orthotics, cushions, heating or ice pads, etc., may help re-
duce interference resulting from discomfort and related
negative emotion. An especially important consideration
is the effect of painonsleep, as sleepdisturbance andresul-
tant daytime fatigue and hypersomnolence may compro-
mise mental efciency. Improved sleep hygiene and phar-
macologic and nonpharmacologic treatment of problems
with sleep initiation and maintenance may be appropriate
prerequisite interventions prior to conducting neuropsy-
chological evaluation.
Clarifying the presence and intensity of momentary
pain (i.e., at the time of an evaluation) is inadequate, as the
concomitants of chronic pain seem to play the more im-
portant role. Symptom checklists that include complaints
often associated with chronic pain (e.g., fatigue) are help-
ful. Sleep surveys may be indicated in specic cases. Ef-
forts to collect corroboratory data from family or others
is advised. The repeated administration of a sustained,
attention-demanding, timed test at the end of a session
may help identify or corroborate possible fatigue-related
decits. Measures to assess motivation seemindicated, not
necessarily to identify malingering, but to help gauge the
effects of chronic pain on the patients ability to sustain
optimal or near optimal effort.
Given evidence that detrimental effects of chronic
pain on cognitive performance may be related to increased
somatic awareness and emotional factors, standard mea-
sures of mood and emotional-personality functioning are
important. Caution should be taken to limit potential sen-
sitizing effects or encouragement of symptom focus and
over-reporting in patients who are already somatically fo-
cused. Identifying emotional suffering, negative illness-
related beliefs, and lifestyle interference that seem dis-
proportionate to pain intensity should increase the level
Chronic Pain 147
of caution in attributing performance decrements to brain
dysfunction from other causes. For this reason, neuropsy-
chological assessment of patients with chronic pain might
include pain-specic evaluation techniques such as visual
analogue scales to assess pain intensity, concomitant neg-
ative emotions, and pain-related beliefs (e.g., Martelli,
Zasler et al., 1999; Wade et al., 1992). As appropriate,
pain behaviors including degree of lifestyle disruption and
possible secondary gain can be assessed using self-report
inventories and structured observation methods suchas the
Psychosocial Pain Inventory (Gotto and Heaton, 1985),
the Multidemensional Pain Inventory (Rudy and Turk,
1987), and the Pain Assessment Battery-Research Edi-
tion (Eimer and Allen, 1995). Notably, the latter includes
specic subscales for both Extreme Beliefs and Symp-
tom Magnication. Additionally, instruments such as the
Kinesiophobia Scale and the Cogniphobia Scales (see
Martelli, Zasler et al., 1999 for tests and review) are useful
for identifying pain-related phobias and avoidance condi-
tioning. These instruments have been designed to assess
pain and anxiety-based avoidant behavior with regard to
physical and cognitive exertion, respectively; high scores
can be expected to result in reduced effort on physically
and/or cognitively demanding tasks. Subsequent to ruling
out malingering, these conditions are treatable through
combination therapies that include such anxiety reduc-
tion procedures as psychoeducation, graduated exposure,
and cognitive reinterpretation. In general, accommoda-
tions that focus on reducing anxiety can improve perfor-
mance during neuropsychological assessment. Litigation
is another variable that inuences test performance and
should always be considered in light of other available
information in interpreting neuropsychological test data.
Tests of motivation and response bias, and probably pain
inventories, should be employed when a chronic pain pa-
tient is in litigation or seeking wage replacement benets.
In general, the clinician should be prepared to assess
chronic pain and its concomitants when the complaint is
salient and the limitations in everyday functioning and
test performance seem atypical for the neurologic condi-
tion, or there is reason to suspect that successful adap-
tation is likely to depend upon coping with pain-related
symptomatology.
CONCLUSIONS
An understanding of the effects of chronic pain on
cognitive functioning is necessary to both appreciate the
range of problems associated with a common clinical syn-
drome and to consider the potential role of pain and asso-
ciated symptoms in the presentation of patients with doc-
umented or presumptive brain injury. Numerous studies
reviewed here have demonstrated neuropsychological im-
pairment in patients with chronic pain, particularly on
measures assessing attentional capacity, processing speed,
and psychomotor speed. In some studies, impairment has
been related to greater pain intensity and to the involve-
ment of head and neck areas or a higher incidence of symp-
toms referable to a cervicoencephalic syndrome. There
is also support for an association between impairment and
other symptoms often associated with pain such as mood
change, increased somatic awareness, sleep disturbance,
andfatigue. However, researchtodate has not exploredina
comprehensive manner the interrelationships among these
variables, nor addressed the multidimensional aspects of
the pain experience. Despite some suggestive ndings,
further studies are needed to clarify the variables that me-
diate the impact of pain on neuropsychological function-
ing and the unique role of various symptoms associated
with chronic pain.
REFERENCES
Andary, M. T., Crewe, N., Ganzel, S. K., Haines, P. C., Kulkarni, M. R.,
Stanton, D. F., Thompson, A., and Yosef, M. (1997). Traumatic
brain injury/chronic pain syndrome: A case comparison study. The
Clinical Journal of Pain 13: 244250.
Armstrong, C., Lewis, T., DEsposito, M., and Freundlich, B. (1997).
Eosinophilia-myalgia syndrome: Selective cognitive impairment,
longitudinal effects, and neuroimaging ndings. Journal of Neurol-
ogy, Neurosurgery and Psychiatry 63: 633641.
Astrand, N. E. (1987). Medical, psychological, and social factors as-
sociated with back abnormalities and self reported back pain: A
cross-sectional study of male employees in a Swedish pulp and
paper industry. British Journal of Industrial Medicine 44: 327
336.
Atkinson, J. H., Ancoli-Israel, S., Slater, M. A., Garn, S. R., and Gillin,
J. C. (1988). Subjective sleep disturbance in chronic pain. The Clin-
ical Journal of Pain 4: 225232.
Bell, B. D., Primeau, M., Sweet, J. J., and Loand, K. R. (1999). Neu-
ropsychological functioning in migraine headache, non-headache
chronic pain, and mild traumatic brain injury patients. Archives of
Clinical Neuropsychology 14: 111.
Coderre, T. J., Katz, J., Vaccarino, A. L., and Melzack, R. (1993). Con-
tribution of central neuroplasticity to pathological pain: Review of
clinical and experimental studies. Pain 44: 259285.
Cote, K. A., and Moldofsky, H. (1997). Sleep, daytime symptoms, and
cognitive performance in patients with bromyalgia. The Journal
of Rheumatology 24: 1423.
Denys, P., Azouvi, P., Denormandi, P., and Samuel, C. (1996). Late cog-
nitive and behavioral improvement following treatment of disabling
orthopaedic complications of a severe closed head injury. Brain In-
jury 10: 149153.
Dikmen, S., McLean, A., and Temkin, N. (1986). Neuropsychological
and psychosocial consequences of minor head injury. Journal of
Neurology, Neurosurgery, and Psychiatry 49: 12271232.
DiPiero, V., Jones, A. K., Iannotti, F., Powell, M., Perani, D., Lenzi,
G. L., and Frackowiak, R. S. (1991). Chronic pain: A PET study of
the central effects of percutaneous high cervical cordotomy. Pain
46: 912.
DiStefano, G., and Radanov, B. P. (1995). Course of attention and mem-
ory after common whiplash: A two-years prospective study with
age, education and gender pair-matched patients. Acta Neurologica
Scandinavia 91: 346352.
Dufton, B. D. (1989). Cognitive failure and chronic pain. International
Journal of Psychiatry in Medicine 19: 291297.
Eccleston, C. (1994). Chronic pain and attention: A cognitive approach.
British Journal of Clinical Psychology 33: 535547.
Eccleston, C. (1995). Chronic pain and distraction: An experimental
investigation into the role of sustained and shifting attention in
the processing of chronic persistent pain. Behavioral Research and
Therapy 33: 391405.
Eccleston, C., and Crombez, G. (1999). Pain demands attention: A
cognitive-affective model of the interruptive function of pain. Psy-
chological Bulletin 125: 356366.
Eccleston, C., Crombez, G., Aldrich, S., and Stannard, C. (1997). Atten-
tion and somatic awareness in chronic pain. Pain 72: 209215.
Eimer, B. N., and Allen, L. M. (1995). Psychological Assessment and
Treatment of Chronic Pain and Related Disability. Users Guide
to the Pain Assessment Battery-Research Edition, Durham, NC,
CogniSyst, Inc.
Getto, C. J., and Heaton, R. K. (1985). Psychosocial Pain Inventory.
Odessa, FL, Psychological Assessment Resources.
Gimse, R., Bjorgen, I. A., Tjell, C., Tyssedal, J. S., and Bo, K. (1997).
Reduced cognitive functions in a group of whiplash patients with
demonstrated disturbance in the posture control system. Journal of
Clinical Experimental Neuropsychology 19: 838849.
Goldberg, M. B., Mock, D., Ichise, M., Proulx, G., Gordon, A.,
Shandling, M., Tsai, S., and Tenenbaum, H. C. (1996). Neuropsy-
chologic decits and clinical features of post-traumatic temporo-
mandibular disorders. Journal of Orofacial Pain 10: 126140.
Grace, G. M., Berg, M. A., and Nielson, W. (1995). Assessment of
attention, concentration, and memory in patients with bromyalgia.
Journal of the International Neuropsychological Society 1: 137.
Grace, G. M., Nielson, W. R., Hopkins, M., and Berg, M. A. (1999).
Concentration and memory decits in patients with bromyalgia
syndrome. Journal of Clinical and Experimental Neuropsychology
21: 477487.
Grigsby, J., Rosenberg, N. L., and Busenbark, D. (1995). Chronic pain is
associated with decits in information processing. Perceptual and
Motor Skills 81: 403410.
Harkins, S. W., Price, D. D., and Braith, J. (1989). Effects of extraversion
and neuroticism on experimental pain, clinical pain, and illness
behavior. Pain 36: 209318.
Hinnant, D. W. (1994). Psychological evaluation and testing. In Tollison,
D. C., Satterwhite, J. R., and Tollison J. W., (eds.), Handbook of
Chronic Pain Management, Williams & Wilkins, Baltimore, MD,
pp. 1835.
Jamison, R. N., Sbrocco, T., and Parris, W. C. V. (1988). The inuence
of problems with concentration and memory on emotional distress
and daily activities in chronic pain patients. International Journal
of Psychiatry in Medicine 18: 183191.
Jarvis, P., and Kooken, R. (1998). Fibromyalgia: Acase study illustrating
the relationship between pain and neuropsychological test perfor-
mance. The Bulletin of the National Academy of Neuropsychology
14: 79.
Kaplan, R., Meadows, M., Vincent, L., Logigian, E., and Steere, A.
(1992). Memory impairment and depression in patients with lyme
encephalopathy: Comparison with bromyalgia and nonpsychoti-
cally depressed patients. Neurology 42: 12631267.
Kewman, D. G., Vaishampayan, N., Zald, D., and Han, B. (1991). Cog-
nitive impairment in musculoskeletal pain patients. International
Journal of Psychiatry in Medicine 21: 253262.
King, D. A., Cox, C., Lyness, J. M., and Caine, E. D. (1995). Neuropsy-
chological effects of depression and age in an elderly sample: A
conrmatory study. Neuropsychology 9: 339408.
Kulich, R. J., and Baker, W. B. (1999). A guide for psychological testing
and evaluation for chronic pain. In Aranoff, G. M. (ed.), Evaluation
and Treatment of Chronic Pain, Williams and Wilkins, Baltimore,
MD, pp. 301312.
Landro, N. I., Stiles, T. C., and Sletvold, H. (1997). Memory function-
ing in patients with primary bromyalgia and major depression
and healthy controls. Journal of Psychosomatic Research 42: 297
306.
Lake, A. E., Branca, B., Lutz, T. E., and Saper, J. R. (1999). Headache
level during neuropsychological testing and test performance in
patients with chronic post-traumatic headache. Journal of Head
Trauma Rehabilitation 14: 7080.
Levin, H. S., Mattis, S., Ruff, R., Eisenberg, H. M., Marshall, L. F.,
Tabaddor, K., High, W. M., and Frankowski, R. F. (1987). Neu-
robehavioral outcome following minor head injury: A three-center
study. Journal of Neurosurgery 66: 234243.
Loeser, J. D. (1982). Concepts of pain. In Stanton-Hicks, M., and Boas,
R. (eds.), Chronic Low Back Pain, Raven, New York, pp. 145
148.
Lorenz, J., Beck, H., and Bromm, B. (1997). Cognitive performance,
mood and experimental pain before and during morphine-induced
analgesia in patients with chronic non-malignant pain. Pain 73:
369375.
Martelli, M. F., Grayson, R., and Zasler, N. D. (1999). Post traumatic
headache: Psychological and neuropsychological issues in assess-
ment and treatment. Journal of Head Trauma Rehabilitation 1: 49
69.
Martelli, M. F., Zasler, N. D., Mancini, A. M., and MacMillan, P.
(1999). Psychological assessment and applications in impairment
and disability evaluations. In May, R. V., and Martelli, M. F. (eds.),
Guide to Functional Capacity Evaluation with Impairment Rat-
ing Applications, NADEP Publications, Richmond, VA, pp. 3-1
3-84.
Melzack, R. (1996). Gate control theory. Pain Forum 5: 128138.
Melzack, R. (1999). From the gate to the neuromatrix. Pain Supplement
6: 121126.
Melzack, R., and Wall, P. D. (1965). Pain mechanisms: A new theory.
Science 150: 971979.
Miller, L. (1990). Chronic pain complicating head injury recovery: Rec-
ommendations for clinicians. Cognitive Rehabilitation 8: 1219.
Morin, C. M., Gibson, D., and Wade, J. (1998). Self-reported sleep and
mood disturbance in chronic pain patients. The Clinical Journal of
Pain 14: 311314.
Mountz, J. M., Bradley, L. A., and Alarc on, G. S. (1998). Abnormal
functional activity of the central nervous system in bromyal-
gia syndrome. American Journal of Medical Science 315: 385
396.
Mountz, J. M., Bradley, L. A., Modell, J. G., Alexander, R. W., Triana,
A., Aaron, L. A., Stewart, K. E., Alarc on, G. S., and Mountz, J. D.
(1995). Fibromyalgia in women: Abnormalities of regional cerebral
blood ow in the thalamus and the caudate nucleus are associated
with low pain threshold levels. Arthritis and Rheumatology 38:
926938.
Nicholson, K. (1998, November). The neuropsychology of pain (Towards
a neuropsychology of pain?). Paper presented at the meeting of the
National Academy of Neuropsychology, Washington, DC.
Pilcher, J. J., and Huffcutt, A. L. (1996). Effects of sleep deprivation on
performance: A meta analysis. Sleep 19: 318326.
Pincus, T., Fraser, L., and Pearce, S. (1998). Do chronic pain patients
Stroop on pain stimuli? British Journal of Clinical Psychology
37: 4958.
Pollina, D. A., Kaufman, L. D., Masur, D. M., and Krupp, L. B. (1998).
Pain, fatigue, and sleep in eosinophilia-myalgia syndrome: Rela-
tionship to neuropsychological performance. Journal of Neuropsy-
chiatry and Clinical Neuroscience 10: 338342.
Price, D. D. (1988). Psychological and neural mechanisms of pain,
Raven, New York.
Puca, F. M., Prudenzano, A. M. P., Savarese, M., Genco, S., and
Specchio, L. M. (1997). Stress, mood disorders and memory in
headache. International Journal of Clinical Pharmacology Resi-
dency 17: 111114.
de Quervin, D. J., Roozendaal, B., and McGraugh, J. L. (1998). Stress
and glucocorticoids impair retrieval of long-term spatial memory.
Nature 394: 787790.
Radanov, B. P., DiStefano, G., Schnidrig, A., Sturzenegger, M., Genco,
S., and Augustiny, K. F. (1993). Cognitive functioning after com-
mon whiplash. Acontrolled follow-up study. Archives of Neurology
50: 8791.
Chronic Pain 149
Radanov, B. P., Dvorak, J., and Valach, L. (1992). Cognitive decits
in patients after soft tissue injury of the cervical spine. Spine 17:
127131.
Radanov, B. P., Hirlinger, I., DiStefano, G., and Valach, L. (1992). At-
tentional processing in cervical spine syndromes. Acta Neurologica
Scandinavia 85: 358362.
Rudy, T. E., and Turk, D. C. (1989). Multiaxial assessment of pain:
Multidimensional pain inventory computer program user manual
version 2.1, University of Pittsburgh, Pittsburgh, PA.
Schmand, B., Lindeboom, J., Schagen, S., Heijt, R., Koene, T., and
Hamburger, H. L. (1998). Cognitive complaints in patients after
whiplash injury: The impact of malingering. Journal of Neurology,
Neurosurgery, and Psychiatry 64: 339343.
Schnurr, R. F., and MacDonald, M. R. (1995). Memory complaints in
chronic pain. The Clinical Journal of Pain 11: 103111.
Schwartz, D. P., Barth, J. T., Dane, J. R., Drenan, S. E., DeGood, D. E.,
and Rowlingson, J. C. (1987). Cognitive decits in chronic pain pa-
tients with and without a history of head/neck injury: Development
of a brief screening battery. The Clinical Journal of Pain 3: 94101.
Sendrowski, D. P., Buker, E. A., and Gee, S. S. (1997). An investiga-
tion of sympathetic hypersensitivity in chronic fatigue syndrome.
Optometry and Visual Science 74: 660663.
Sletvold, H., Stiles, T. C., and Landro, N. I. (1995). Information process-
ing in primary bromyalgia, major depression and healthy controls.
Journal of Rheumatology 22: 137142.
Taylor, A. E., Cox, C. A., and Mailis, A. (1996). Persistent neuropsy-
chological decits following whiplash: Evidence for chronic mild
traumatic brain injury? Archives of Physical Medicine and Reha-
bilitation 77: 529535.
Treede, R. D., Kenshalo, D. R., Gracely, R. H., and Jones, A. (1999).
The cortical representation of pain. Pain 79: 105111.
Tsushima, W. T., and Newbill, B. A. (1996). Effects of headaches during
neuropsychological testing of mild head injury patients. Headache
36: 613615.
Turk, D. C., and Holzman, A. D. (1986). Chronic pain: Interfaces among
physical, psychological and social parameters. In Holzman, A. D.,
and Turk, D. C. (eds.), Pain Management: A Handbook of Psy-
chological Treatment Approaches, Pergammon Press, New York,
pp. 19.
Turk, D. C., and Rudy, T. E. (1987). Towards comprehensive assessment
of chronic pain patients. Behavioral Research & Therapy 25: 237
249.
Veill, H. O. F. (1997). A preliminary prole of neuropsychological
decits associated with major depression. Journal of Clinical and
Experimental Psychology 19: 587603.
Vernon-Wilkinson, R., and Tuokko, H. (1993). The inuence of pain
symptoms on neuropsychological test scores. Archives of Clinical
Neuropsychology 9: 2.
Vogt, B. A., Derbyshire, S., and Jones, A. K. (1996). Pain processing in
four regions of human cingulate cortex localized with co-registered
PET and MR imaging. European Journal of Neuroscience 8: 461
1473.
Wade, J. B., Dougherty, L., Hart, R. P., Rai, A., and Price, D. D. (1992).
Acanonical correlation analysis of the inuence of neuroticismand
extraversion on chronic pain, suffering, and pain behavior. Pain 51:
6773.
Walsh, N. E., Dumitu, D., Ramanurthy, S., and Schoenfeld, L. S. (1988).
Treatment of the patient with chronic pain. In DeLisa, J. A., Currie,
D. M., Gans, B. M., Gatens, P. F., Leondard, J. A., and McPhee,
M. C. (eds.), Rehabilitation Medicine: Principles and Practice, J.
B. Lippincott, Philadelphia, PA.
Woolf, C. J., and Thompson, S. W. N. (1991). The induction and mainte-
nance of central censitization is dependent of N-methyl D-aspartic
acid receptor activation: Implications for treatment of post-injury
pain hyperalgesic states. Pain 44: 293299.
Ziegler, D. K., and Paolo, A. M. (1995). Headache symptoms and psy-
chological prole of headache-prone individuals. A comparison of
clinic patients and controls. Archives of Neurology 52: 602606.

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