chronic pain & neuropsychological functioning (np rev 2000)

7/30/2019 Chronic Pain & Neuropsychological Functioning (NP Rev 2000)

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Neuropsychology Review, Vol. 10, No. 3, 2000

Chronic Pain and Neuropsychological Functioning

Robert P. Hart,1,3 Michael F. Martelli,2 and Nathan D. Zasler3

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 identified that demonstrate neuropsychological

impairment in patients with chronic pain, particularly on measures assessing attentional capacity,

processing speed, and psychomotor speed. Despite suggestive findings, further studies are needed to

clarify the variables that mediate the impactof 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 defined 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 influences. Variability in pain responses are common

and appear to reflect 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 whichtreatment is aimed at correcting the pathological process;

and (d) the relative absence of marked psychosocial

1Medical College of Virginia of Virginia Commonwealth University.2Concussion Care Centre of Virginia, Ltd.3Pinnacle Rehabilitation, Tree of Life, LLC, Richmond, Virginia.4To 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 studiesthat 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


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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 findings as the most sensitive sign of

brain injury. The judgments made have far-reaching im-

plications in terms of financial, 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 deficits from a known CNS disorder or pain

causing deficits that, in turn, raiseconcern about an uniden-

tified 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 deficiencies in the

absence of other identifiable causes, Jarvis and Kooken

(1998) describe a patient diagnosed with fibromyalgia

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 unspecified. Some studies focused

on specific pain syndromes such as fibromyalgia, rheuma-

tism (Barre-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 painsubgroups, 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 deficits.


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Chronic Pain 133

Table I. Summary of Studies

TBI or CNS

Authors Clinical groups disorder Normal controls Medication Litigation

Bell, Primeau,

Sweet, and

Lofland (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 takingmedication 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 influence 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)


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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 ofconsciousness

n = 10 Yes Patients covered by

insurance that

compensates for

economic loss andnone 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 findings

Bell, Primeau,

Sweet, and

Lofland (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. NavalHealth Research

Centers Mood

Scale

Simulated

multitask

office

procedure

Speed of serialaddition/

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 acomputerized battery.

Patients showed lighter

sleep (stage 1) on

polysomnography.

Stage 1 sleep and

somatic components of

the Beck Inventory

covariedwith aspects of

test performance

(Continued)


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Chronic Pain 135




DiStefano and

Radanov (1995)

010 scale Well-being scale PASAT

TMT

Digit span

Corsi-Block

TappingNumber

Connection Test

CVLT

Symptomatic patients

performed worse than

asymptomatic onPASAT. 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 andmood 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

Modified 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, andreported 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)


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Grace, Nielson,

Hopkins, and

Berg (1999)

Pain Severity Scale from

Multidimensional Pain

Inventory

State-Trait Anxiety

Centre for

Epidemiological

StudiesDepression

Scale (CES-D)

WMS-R General

Memory and

Delayed

RecallIndices

PASAT

WMS-R Attention

Concentration

Index

RAVLT Totalrecall trials 15

Symbol Digit

Modalities Test

Pain patients reported

more sleep disturbance

on Pittsburgh Sleep

Quality Index, and self-ratedmemory problems

that exceeded objective

deficits. 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

InventoryMMPI

Pain patients performed

similar to depressedpatients 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)

Visu al analog scale Beck Depression

Inventory

Randt Memory

Test

Code MemoryTest

Word Fluency

Digit Span

Kimura Recurring

Figures TestIncidental Memory

(RANDT)

Pain patients with a

history of major

depression wereimpaired 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)

Visu al analog scale 5 visu al analo g

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

influenced

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)


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Chronic Pain 137




Radanov, Hirlinger,

DiStefano, and

Valach (1992)

No Freiburg

Personality

Inventory

Well-being ScaleDSM-III-R

diagnosis

PASAT

TMT

Number Connection Test Both groups of pain

patients were impaired

based on norms. Poor

performance on PASATwas 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 tobe 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 ahistory 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

matchedon 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

intensitynor 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 = reactiontime; 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

chiefly from low back pain. Approximately 25% of the pa-

tients were rated as demonstrating possible or mild deficits

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 deficits 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


8/19


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 deficit 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, and energy level) and a 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 patientssuffered 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 low levels

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

significantly 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 finding 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 significantly correlated with reaction time, although

the latter negative finding 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 (inan alternating sequence)between responding with

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 similarchronic 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 fibromya-

lgia. Importantly, fibromyalgia is characterized by chronic

fatigue and sleep disturbance, as well as pain, and patients

often suffer from significant mood disturbance. In a pre-

liminary study, Grace, Berg, and Nielson (1995) found

evidence of mild memory impairment in patients with

fibromyalgia 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) fibromyalgia patients referred

to a treatment program performed 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 deficits was interpreted asindicating a primary deficit 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.


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Chronic Pain 139

Sletvold, Stiles, and Landro (1995) found deficits on

testsrequiring attention, rapidinformationprocessing, and

psychomotor speed in patients with fibromyalgia. Patients

with fibromyalgia 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 wasascer-

tained using the Beck Depression Inventory and the Struc-

tured Clinical Interview for DSM-III-R. The fibromyalgia

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 deficits in the fibromyalgia 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 controlgroup on Digit Symbol and the PASAT. The subgroup

of fibromyalgia patients without a history of major de-

pression performed similar to fibromyalgia 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 fi-

bromyalgia patients who had a lifetime history of major

depression showed memoryimpairment 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 fluency. Impairments were not demonstrated on

Digit Span or KimuraRecurring 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

fibromyalgia 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 office procedure involving short-term memory for a list of letters, addition problems, visual

monitoringof 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 nonsignificant 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 DepressionInventorycovaried with performance

across all cognitive tests, as well as with ratings of pain

and fatigue. Theauthors 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 fluency. Potential medicationeffects 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 back region. Thepain patients displayeddeficits 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 difficulties on

tests of simple motor speed (finger-tapping) and motor co-

ordination (finger-to-nose testing), and no impairment on

tests of short-term visual memory (immediate recall of asequential 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


10/19


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

consonanttriadsafter intervalsranging from018 seconds

filled 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 causedby 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 whohad suf-

fered a whiplash injury. Poor performance on the PASAT

was associated with lower self-ratings of emotional well-

being in both groupsand with higherlevels of self-reported

nervousness in the whiplash group.

In contrast to the studies cited above, Bell, Primeau,

Sweet, and Lofland (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

from WMS-R), and attention/psychomotor speed(PASAT,

Stroop Test, Trail-Making Test). The chronic pain patients

were nearly all from a specialty clinic, and the majority

(65%) suffered from back pain. Depression level fell in the

mild range. Fifteen percent of the pain group performedat 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 significant. Because comparisons to normative

data were not reported for individual tests, it is unclear

whether the PASAT (which in this study included only the

first 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 fibromyalgia 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 significant 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/ Neck Pain andAssociated Symptoms

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 difficult to interpret the negative finding

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 TMD patients performed worse thanidiopathic 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


11/19

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 anyof 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 from mild 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.

Thestudy by Schmand etal. (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 below the

cutoff performed about as poorly as patients with a history

of serious head injury (mean Glasgow Coma 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 thepatients with idiopathic TMD, but 38% of the patients

with posttraumatic TMD demonstrated painreactions 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-

graphicallymatched patients selected from thosewho were

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 significantly worse onthe 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

washigher in thesymptomaticgroupat follow-up intervals

than that of asymptomatic patients at baseline, and pain

intensity was shown to significantly 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, Dvoraket 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 from repeat testing at

the end of the session were unchanged in patients with id-iopathic TMD but decreased significantly in patients with

posttraumatic TMD, suggesting that fatigue was a factor

contributingto thedeficits in thelatter group.In thefollow-

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


12/19


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 significantly 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 Barre-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 attentionalproblems 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 flush, increased

heart rate). Other research hasshown 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, and Speechio, 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 flexibility (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 efficiency. In thestudy by Radanov, Dvorak et al. (1992) most patients

showing impairment on the PASAT had a distinct symp-

tom complex 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 significantly higher number of somatic

complaints on the SCL-90 modified for use with TBI

populations. Deficits in attention and memory have been

demonstratedin whiplash patients selected for chronic dis-

turbancesin theposture control systemas demonstratedon

The Smooth Pursuit Neck Torsion Test (Gimse, Bjorgen,

Tjell, Tyssedal, and Bo, 1997). The patients had deficits

on the Rey Auditory Verbal Learning Test (learning andretention) 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 system and the associatedinfluence on the reticular activating system, may affect

attention.

NONCLINICAL PAIN POPULATIONS

In contrast to thestudies 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 neuroticism derived fromques-

tions on a medical index showed significant 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).


13/19

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 findings in patients with chronic pain syndromesdoes 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 sufficient 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 didworseon neuropsychologicaltests than those

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 mildTBI 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-betafibers inhibits transmission to the T-cells, thus

closing the gate. Activation of small A-delta and C fibers

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 fibers 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 fibers 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; specifically, nocicep-

tor specific (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 fibers 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 influx 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

etal. (1999)foundconsistentevidence of regional cerebral


14/19


blood flow abnormalities in persons with chronic pain

(i.e., Di Piero et al., 1991; Mountz, Bradley, and Alarcon,

1998; Mountz et al., 1995; Sendrowski, Buker, and Gee,

1997). Abnormalities have been reported for fibromyal-

gia, high cervical cordotomy, and other muscular and non-

neurologic disorders. These findings have been interpreted

as offering support to the idea that chronic pain exertsa potentially disruptive physiological effect on cerebral

functioning in general and therefore in theory may inter-

fere with cognitivefunctioning. 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 clarified.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 pain related to stress

and the associated increase in systemic, and more impor-

tantly, central glucocorticoid production likely also play a

role in impairmentof 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 significant or more severe pain requires conscious cen-

tral attentional control and that subjects with low pain 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) haveconceptualized pain as an attention-demanding percep-

tual stimulus, and attention as a finite 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. Otherinvestigators have posited that attentionalbiases 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., presenceof 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 nonsignificant 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


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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 influence 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

nonspecific 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

factorsother than pain intensity and location. In the case oftrauma 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 asother 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 generalmedical-dental and psychotherapy patient groups without

pain-related problems, and that partialing out the effect of

mood significantly 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 emotionaldistress (e.g., Atkinson, Ancoli-Israel, Slater, Garfin, 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 influence 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 deficits. 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 profile to that seen

in brain injury. Even more significant deficits have beenreported 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 identified in this review would provide valuable

information about which factors uniquely influence neu-

ropsychological functioning in chronic pain patients.


16/19


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, Rafii, and Price, 1992). The first 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 homeand during clinical interview).

Studies of cognitive functioning in patients with

chronic pain have focused primarily on ratings of pain in-

tensity. Theoretically, laterstages 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 influ-

ence of pain on cognition. Examples of identified 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 measurementof cognitivefunctions 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

findings 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 injuryin patients with chronic pain. In cases where pain and re-

lated symptomatology have not received specific and/or

appropriate treatment focus, consideration should be 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 useorthotics, cushions, heating or ice pads, etc., may help re-

duce interference resulting from discomfort and related

negative emotion. An especially important consideration

is theeffect of pain on sleep,as sleep disturbance andresul-

tant daytime fatigue and hypersomnolence may compro-

mise mental efficiency. 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 specific 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

deficits. Measures to assess motivationseem indicated, 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 chronicpain 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


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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-specific 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 behaviorsincluding degree of lifestyle disruption and

possible secondary gain can be assessed using self-report

inventories and structured observation methods such as 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

specific subscales for both Extreme Beliefs and Symp-

tom Magnification. Additionally, instruments such as the

Kinesiophobia Scale and the Cogniphobia Scales (see

Martelli, Zasler et al., 1999 fortests 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 influences 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 benefits.

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.

chronic pain & neuropsychological functioning (np rev 2000)

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