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 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 examine 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 emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Pain is generally considered a multidimensional subjective experience mediated by emotion, attitudes, and other perceptual inuences. Variability in pain responses are common and appear to reect complex biopsychosocial interactions between genetic, developmental, cultural, environmental, and psychological factors (Hinnant, 1994; Turk and Holzman, 1986). Acute pain, or pain occurring shortly after injury, is typically characterized by (a) relatively discrete neuroanatomic pathways mediating effects of somatic injury; (b) transmission of information with survival value that initiates protective physiological mechanisms (against injury 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. Care Centre of Virginia, Ltd. 3 Pinnacle Rehabilitation, Tree of Life, LLC, Richmond, Virginia. 4 To whom correspondence should be addressed at Department of Psychiatry, Medical College of Virginia of Virginia Commonwealth University, P.O. Box 980268, Richmond, Virginia 23298-0268.
2 Concussion

changes or behavioral changes disproportionate to pain intensity. In contrast, chronic pain persists long after injury (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 protracted course of medication use and minimally effective medical services; and (d) marked behavioral and emotional 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 experience. 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 examine the potential contribution of persistent pain and associated symptoms to impaired performance on neuropsychological tests. An understanding of the effects of pain on cognitive functioning has important implications for appreciating the range of problems reported by patients with pain syndromes, for differential diagnosis, and 131
1040-7308/00/0900-0131$18.00/0
C

2000 Plenum Publishing Corporation

132 for evaluation in cases of atypical presentation by patients with brain impairment. Understanding the range of problems associated with chronic pain seems imperative when its prevalence in the general population is considered. 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 neuropsychological test ndings as the most sensitive sign of brain injury. The judgments made have far-reaching implications in terms of nancial, vocational, treatment, and disability issues. Traumatic injuries frequently affect multiple parts of the body, although headache is the most frequent 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 inferences 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 patient for evaluation, possibilities to consider include pain exacerbating decits from a known CNS disorder or pain causing decits that, in turn, raise concern about an unidentied 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 important 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 ventricular enlargement on CT scan, these patients exhibited greater cognitive impairment. Patients with pain symptoms performed less well on tests of intelligence, reasoning, and memory (WAIS-R Performance I.Q.; Ravens Progressive Matrices; Category Test; and Benton Visual Retention Test). The patients with pain symptoms also reported higher levels of psychological distress on symptom inventories, although the authors did not examine whether psychological distress was an important mediating variable. 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

Hart, Martelli, and Zasler 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 Perception Test). OVERVIEW OF STUDIES Table I summarizes the clinical studies that included a group of chronic pain patients without neurologic disorders or injuries involving head trauma or loss of consciousness (one study in which 13% of the sample had a short loss of consciousness is included). The table includes 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 multiple sites, or whiplash injuries. The type of pain (e.g., myofascial) was often unspecied. Some studies focused on specic pain syndromes such as bromyalgia, rheumatism (Barr e-Lieou Syndrome), or temporomandibular disorder (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 additional 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 fatigue 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 comprehensive 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
Table I. Summary of Studies
Authors Bell, Primeau, Sweet, and Loand (1999) Cote and Moldofsky (1997) DiStefano and Radanov (1995) Clinical groups Chronic pain syndromes (n = 20) Fibromyalgia (n = 10) Patients with a psychiatric disorder were excluded Whiplash injury patients symptomatic at 2-year follow-up (n = 21) No TBI or CNS disorder Normal controls No Medication Litigation >50% seeking compensation

133

No

n=9

No patients taking medication at the time 19% using medication that might inuence test performance

No patient had head contact injury or alteration of consciousness No

No

No patient initiated litigation during follow-up period

Eccleston (1994)

Chronic benign pain at mixed sites Study 1 (n = 20) Study 2 (n = 24) Chronic intractable benign pain at mixed sites (n = 22) Chronic pain at mixed sites (n = 46)

Study 1 (n = 10) Study 2 (n = 12)

Intermittent use of opiate-based analgesics Study 140% Study 236% 45% opiates

Eccleston (1995)

No

n = 11

Eccleston, Crombez, Aldrich, and Stannard (1997)

No

No

13% opioid medication, 24% combination of nonsteriodal analgesic, antidepressant or opioid medication Yes

Gimse, Bjorgen, Tjell, Tyssedal, and Bo (1997)

Chronic whiplash patients with disturbances in the posture control system (n = 23) Chronic TMD post whiplash injury (n = 13), Chronic idiopathic TMD (n = 14)

13% had a short period of unconsciousness at the time of injury Whiplash patients did not experience loss of consciousness at injury No

n = 26

13% in litigation, 48% awaiting compensation from insurance Virtually all subjects recruited following adoption of no fault insurance

Goldberg et al. (1996)

No

No patients taking medication known to affect CNS functioning

Grace, Berg, and Nielson (1995) Grace, Nielson, Hopkins, and Berg (1999)

Fibromyalgia (n = 15)

n = 15

No patients taking medication known to affect CNS functioning Approximately half the patients taking antidepressants or anxiolytics, but none taking a narcotic analgesic No patients taking medications known to affect CNS functioning

Fibromyalgia (n = 30) Patients with clinical depression were excluded

No

n = 30

Grigsby, Rosenberg, and Busenbark (1995)

Chronic pain syndromes (n = 19) Pain was myofascial for nearly all 42% had whiplash injuries Fibromyalgia (n = 11)

No

No

Kaplan, Meadows, Vincent, Logigian, and Steere (1992) Kewman, Vaishampayan, Zald, and Han (1991) Landro, Stiles, and Sletvold (1997) Lorenz, Beck, and Bromm (1997) Pincus, Fraser, and Pearce (1998)

No

No

Musculoskeletal pain at mixed sites (n = 73)

No

No

Excluded patients taking narcotic analgesics day of exam No patients with routine use of opioids

Fibromyalgia (n = 25) Chronic pain syndromes (n = 6) Chronic pain syndromes (n = 20)

No No No

n = 18 No n = 20

(Continued )

134
Table I. (Continued )
Authors Radanov et al. (1993) Clinical groups Whiplash injury patients symptomatic at 6-month follow-up (n = 31) TBI or CNS disorder No patients had head contact injury or alteration of consciousness Normal controls n = 10 Yes Medication

Hart, Martelli, and Zasler

Litigation Patients covered by insurance that compensates for economic loss and none initiated litigation during follow-up 20% completing tests examined in connection with insurance claims

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) Cervical spine syndrome from rheumatism (n = 28), chronic whiplash injury (n = 54)

43% with UCS but none with LCS reported short duration impairment of consciousness at injury Whiplash patients did not suffer head trauma or a loss of consciousness Patients with TBI or loss of consciousness were excluded from whiplash group No No Whiplash patients did not suffer impact injuries or a loss of consciousness Assessment of emotion Beck Depression Inventory

No

No patients taking prescribed medication

Radanov, Hirlinger, DiStefano, and Valach (1992)

No

No patients taking prescribed medications

Schmand et al. (1998)

Chronic whiplash injury (n = 108; 43 scored below cutoff on malingering test and were a separate group) Mixed chronic pain syndromes (n = 17) Fibromyalgia (n = 25) Chronic pain syndromes (n = 24), chronic whiplash injury (n = 15)

n = 46

31% analgesics, 7% benzodiazepenes, 2% combination of above

33% evaluated as part of litigation, 89% with damage claim or workmans compensation claim 18% Whiplash patients had been referred for a medical-legal evaluation

Schwartz et al. (1987) Sletvold, Stiles, and Landro (1995) Taylor, Cox, and Mailis (1996)

No n = 18 No

No patient taking medications known to affect CNS functioning

Authors Bell, Primeau, Sweet, and Loand (1999)

Pain ratings 7-point scale

Tests sensitive to effects of pain

Tests not sensitive to effects of pain

Other ndings 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) 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 )

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

Chronic Pain

135

Table I. (Continued )
Authors DiStefano and Radanov (1995) Pain ratings 010 scale Assessment of emotion Well-being scale Tests sensitive to effects of pain PASAT TMT Tests not sensitive to effects of pain Digit span Corsi-Block Tapping Number Connection Test CVLT Numerical interference task-dominant response condition Other ndings Symptomatic patients performed worse than asymptomatic on PASAT. Scores on PASAT covaried with pain intensity Patients with high pain intensity performed worse than those with low pain intensity and normal controls. Medication status not related to performance 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 (1994)

Visual analog scale and numerical rating scale

Short-form McGill Pain Questionnaire

Numerical interference tasknondominant response condition (see text) Numerical interference task in which subjects switch (uncued) between dominant and nondominant response conditions on each trial (see text) Numerical interference task-difference in reaction time between dominant and nondominant response conditions (see text) RAVLT PASAT (prolonged ISI)

Eccleston (1995)

Visual analog scale and numerical scale

Hospital Anxiety and Depression (HAD) Scale

Eccleston, Crombez, Aldrich, and Stannard (1997)

Visual analog scale and numerical rating scale

Hospital Anxiety and Depression (HAD) Scale Zung Modied Somatic Perceptions Questionnaire

Patients with both high pain intensity and high somatic awareness performed worse than those with other combinations (i.e., high-low) of pain intensity and somatic awareness, and reported more mood disturbance Whiplash patients performed worse than normal controls. Subgroups with vs. without premorbid health problems and /or current medication use did not differ from one another Whiplash TMD group performed worse than idiopathic TMD group on tests of reaction time, CVLT (immediate but not delayed recall) and Consonant Trigrams Pain patients reported sleep disturbance relative to controls on the Pittsburgh Sleep Quality Index (Continued )

Gimse, Bjorgen, Tjell, Tyssedal, and Bo (1997)

No

No

PASAT (standard ISI) TMT Letter/Category Fluency WAIS-R Block Design and Similarities

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)?

Grace, Berg, and Nielson (1995)

No

No

WMS-R General Memory Index

WMS-R Attention Concentration RAVLT Total recall trials 15 PASAT trials 12

136
Table I. (Continued )
Authors Grace, Nielson, Hopkins, and Berg (1999) Pain ratings Pain Severity Scale from Multidimensional Pain Inventory Assessment of emotion State-Trait Anxiety Centre for Epidemiological Studies Depression Scale (CES-D) Tests sensitive to effects of pain WMS-R General Memory and Delayed Recall Indices PASAT

Hart, Martelli, and Zasler

Tests not sensitive to effects of pain WMS-R Attention Concentration Index RAVLT Total recall trials 15 Symbol Digit Modalities Test

Other ndings Pain patients reported more sleep disturbance on Pittsburgh Sleep Quality Index, and selfrated memory problems that exceeded objective decits. Pain intensity and trait anxiety correlated with tests and partial correlations indicated anxiety as a primary factor Pain patients were impaired based on norms, and also performed less well on than a group of mild to moderate TBI patients 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 32% had impaired performance. Composite score correlated with ratings of pain and disability, and measure of psychological distress 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 Subtle improvement in auditory vigilance in association with reduced pain intensity post treatment Elevated depression and anxiety scores in pain group Correlations between pain intensity and test scores ranged from 0 to .50. Medication use inuenced performance on TMT and PASAT Patients with UCS were impaired on the PASAT based on norms and performed worse than those with LCS (Continued )

Grigsby, Rosenberg, and Busenbark (1995)

No

No

Simple/choice RT

Short-term visual memory (see text)

Kaplan, Meadows, Vincent, Logigian, and Steere (1992)

No

Beck Depression Inventory MMPI

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

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)

Lorenz, Beck, and Bromm (1997)

Visual analog scale

5 visual analog scales

Pincus, Fraser, and Pearce (1998) Radanov et al. (1993)

A numerical rating scale

Hospital Anxiety and Depression (HAD) Scale Well-being Scale Neuroticism Scale from Freiburg Personality Inventory TMT?

Stroop Test

010 scale

Digit Span? Corsi Block Tapping? Number Connection Test? PASAT? Number Connection Test

Radanov, Dvorak, and Valach (1992)

No

No

PASAT?

Chronic Pain
Table I. (Continued )
Authors Radanov, Hirlinger, DiStefano, and Valach (1992) No Pain ratings Assessment of emotion Freiburg Personality Inventory Well-being Scale DSM-III-R diagnosis Tests sensitive to effects of pain PASAT TMT Tests not sensitive to effects of pain Number Connection Test Other ndings

137

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 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 moderatesevere TBI group

Schmand et al. (1998)

No

No

WAIS Digit Symbol Category Fluency AVLT Logical Memory (Rivermead)

TMT Stroop Test

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 Pain patients performed similar to patients with major depression (MD) but worse than normal controls. A subgroup of pain patients without history of MD performed worse than normal controls and similar to a subgroup of pain patients with a history of MD and to MD group 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

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

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

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 from low back pain. Approximately 25% of the patients were rated as demonstrating possible or mild decits on the Paced Auditory Serial Addition Test (PASAT), Trail-Making Test, and/or Controlled Oral Word Association 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 impairment (32%) in patients with musculoskeletal pain who had no history of diagnosed cognitive impairment or

138 degenerative disease. Location of pain was primarily in the low back (33%) or in multiple sites (25%). These investigators 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 ratings of disability (interference with daily activities). The study included ratings of psychological distress (depression, anxiety, irritability, and energy level) and a composite measure of distress was found to correlate with a composite score from the cognitive screening measure. The authors 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 involving 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 status. 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, subjects 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 relationships 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 another group of patients with benign pain, usually involving 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

Hart, Martelli, and Zasler disturbance. A second, more demanding attentional test was also employed. Subjects were required to switch uncued (in an alternating sequence) between responding with the value of the largest digit for each card pair and responding 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 attentional 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 pressing a computer key marked left or right. The variable of interest was the difference in reaction time in processing the nondominant information (number of digits) 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 awareness (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 relationship between level of psychological distress and test performance was not examined. No effect of medication was shown. Several studies have assessed patients with bromyalgia. Importantly, bromyalgia is characterized by chronic fatigue and sleep disturbance, as well as pain, and patients often suffer from signicant mood disturbance. In a preliminary study, Grace, Berg, and Nielson (1995) found evidence of mild memory impairment in patients with bromyalgia relative to a group of normal control subjects. 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 control subjects. In a larger followup study (Grace, Nielson, Hopkins, and Berg, 1999) bromyalgia patients referred to a treatment program performed worse than normal control 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 quality (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 Sletvold, Stiles, and Landro (1995) found decits on tests requiring attention, rapid information processing, and psychomotor speed in patients with bromyalgia. Patients with bromyalgia performed similar to patients with major 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 differences on the Trail-Making Test. This study included no ratings of pain, but the affective state of patients was ascertained using the Beck Depression Inventory and the Structured 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 somatoform disorder. The decits in the bromyalgia group were not simply attributable to comorbid psychiatric disorder, however, as a subgroup of patients without a lifetime 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 depression 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 samples (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 similar to patients with major depression, and were impaired on the Randt Memory Test, the Code Memory Test (recall 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 cognitive performance on a computerized battery of tests in bromyalgia patients. Relative to normal control subjects, the pain patients exhibited more stage 1 sleep on polysomnography, and reported more fatigue, more sleepiness, more intense pain, more negative mood including depression, and a perception of lower accuracy of performance. Patients had a lower composite score and response rate on a simulated multitask ofce procedure involving shortterm memory 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

139 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 pervasive fatigue associated with persistent myalgia most likely account for impaired cognitive performance. Schmand et al. (1998) studied chronic whiplash patients (mean post-injury interval 2 years) either as part of a litigation procedure, or as part of an evaluation at an outpatient clinic. Patients with head injury or loss of consciousness were excluded. Whiplash patients without evidence of underperformance on a test designed to detect malingering performed worse than normal control subjects on some measures of attention and psychomotor speed (Symbol Digit Substitution) but not others (TrailMaking, 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 back region. The pain patients displayed decits in simple and choice reaction time relative to normative data and a group of patients who had suffered a mild to moderate brain injury. The pain group had milder difculties on tests of simple motor speed (nger-tapping) and motor coordination (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

140 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 intensity 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 Trigrams Test. In the latter test, subjects recalled a list of consonant triads after intervals ranging from 018 seconds lled by distracting activity. Both the pain group without trauma and the whiplash group reported symptoms of depression (MMPI-2 scale 2 T scores = 76 and 74, respectively). 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 ratings 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 TrailMaking 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 suffered a whiplash injury. Poor performance on the PASAT was associated with lower self-ratings of emotional wellbeing in both groups and with higher 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 impairment 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 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 statistically 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,

Hart, Martelli, and Zasler 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 patients 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 encephalopathy. 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 disease, 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/Neck Pain and Associated Symptoms Some studies suggest increased vulnerability to cognitive impairment in patients with pain and other symptoms 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 impaired 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 measures of emotional status were reported. Goldberg et al. (1996) contrasted patients whose temporomandibular disorder (TMD) followed a cervical whiplash injury (without loss of consciousness) and those whose TMD was idiopathic. Posttraumatic TMD patients performed worse than idiopathic TMD patients on tests of simple and choice reaction time, verbal learning (California Verbal Learning Test), and short-term memory under interference conditions (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 reaction times. The prevalence of depression based on the

Chronic Pain 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 impairment in patients with pain referable to upper cervical regions following whiplash injury may be because of any of several factors. Goldberg et al. (1996) remarked on the potential similarities between posttraumatic TMD patients and mild TBI patients. Their posttraumatic TMD patients were symptomatic for at least 6 months following injuries that did not involve loss of consciousness. It seems unlikely that brain injury would explain group effects 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 impairments demonstrated within days of common whiplash injury and subtle sequelae in a small subgroup who remain symptomatic for longer periods of time have not been attributed 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 potential confound of malingering or more subtle forms of suboptimal performance in whiplash patients. In a nonrepresentative 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 possible explanation for worse cognitive performance in whiplash-injury patients with symptoms referable to the upper cervical region is that the pain experienced is sometimes 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 with posttraumatic TMD demonstrated pain reactions with palpation of the external masseter, temporalis, and sternocleidomastoid 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

141 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 symptomatic patients (correlations were not provided for individual tests). The correlation between pain intensity and test scores was not attributable to litigation status, but was potentially confounded by individual variations in medication 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 sample, DiStefano and Radanov (1995) contrasted the performance of a subgroup reporting persistent injury-related complaints (18% of sample) and a subgroup of demographically matched patients selected from those who were asymptomatic. Performance on attentional tests was normal in the symptomatic group except for marginally impaired scores on the PASAT and slower times on TrailMaking Part B at 2 years postinjury than at baseline. Symptomatic patients performed signicantly worse on the PASAT than the demographically matched asymptomatic 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 asymptomatic 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 in the symptomatic group at follow-up intervals 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 associated with pain, such as fatigue and mood disturbance, may be greater in those whiplash-injury patients demonstrating relatively more cognitive impairment. For example, 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 cervical syndrome. Goldberg et al. (1996) note that posttraumatic TMD patients tend to suffer from a higher degree of symptoms suggestive of affective disorder, including 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 idiopathic TMD but decreased signicantly in patients with posttraumatic TMD, suggesting that fatigue was a factor contributing to the decits in the latter group. In the followup study of whiplash patients by DiStefano and Radanov (1995), the patients who remained symptomatic and evidenced 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

142 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 example, 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 autonomic reactions (e.g., sweating, facial ush, increased heart rate). Other research has shown a relatively high incidence of anxiety, depression, stress, and somatoform disorder 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 generally within normal limits for a group of 125 chronic posttraumatic headache patients being followed at a treatment center an average of 32 months after mild head/neck injury; the test battery emphasized memory, but included a number of tasks requiring attention, psychomotor speed, and mental exibility (e.g., Controlled Oral Word Association, PASAT, Stroop Test, Symbol Digit Modalities Test, and Trail-Making). Other symptoms associated with a cervicoencephalic syndrome may reduce mental efciency. In the study by Radanov, Dvorak et al. (1992) most patients showing impairment on the PASAT had a distinct symptom complex characterized by a higher incidence of dizziness, 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 posttraumatic group performing worse on neuropsychological tests reported a signicantly higher number of somatic

Hart, Martelli, and Zasler complaints on the SCL-90 modied for use with TBI populations. Decits in attention and memory have been demonstrated in whiplash patients selected for chronic disturbances in the posture control system as demonstrated on 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 interstimulus interval. Other attentional tests (PASAT at a standard interstimulus interval and Trail-Making) showed no impairment. 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, malingering seemed unlikely given the correspondence between neuropsychological data and measures not so easily controlled voluntarily. The authors speculate that disturbances in automatized functions, such as neck proprioceptive input to the postural control system and 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 industry 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 basis 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 attributed to group differences in education and social class. Interestingly, a measure of neuroticism derived from questions on a medical index showed signicant associations with both signs and symptoms of back problems, although no examination of possible correlations with test performance was reported. Although limited data are available, the lack of evidence for cognitive impairment in nonclinical pain populations 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 activities, and hence less likely to impact cognitive functioning. That is, such pain presumably is associated with a different perception, tolerance, or attitude toward the symptoms (Ziegler and Paolo, 1995).

Chronic Pain 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 positive ndings in patients with chronic pain syndromes does not imply that there is necessarily the same relationship between pain symptoms and neuropsychological performance in patients whose CNS disorders or injuries are sufcient to produce persistent neurological and neuroimaging abnormalities; associations between pain and cognitive dysfunction may be attenuated by the overriding impact of structural brain damage. For example, disorders have been described in which pain is a common symptom but no relationship to neuropsychological performance was found, e.g., eosinophilia myalgia syndrome (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 interaction of brain injury and chronic pain. For example, Denys, Azouvi, Denormandi, and Samuel (1996) described a case in which performance on neuropsychological tests paralleled improvement of pain problems in a severe closed head injured patient, and as described earlier, VernonWilkinson and Tuokko (1993) found that TBI patients with pain did worse on neuropsychological tests than those without pain. Several investigators have found considerable 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 picture in TBI but that resolution of the postconcussive syndrome 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 postconcussive sequelae, a small percentage do experience persistent symptomalogy. In these cases, headache or other pain problems may contribute to or explain persistent cognitive complaints.

143 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 C bers increases transmission through these cells, thereby opening the gate. Other mechanisms that are involved in pain mediation include supraspinal inputs that activate large diameter 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 thalamocortical and cortico-limbic links that serve as the anatomical 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 convergence). Two of the three types of dorsal motor neurons are involved in pain transmission; specically, nociceptor specic (NS) cells and wide dynamic range (WDR) cells. Small diameter nociceptive afferents contain excitatory neurotransmitters including glutamate and aspartate as well as neuropeptides such as substance P and calcitonin gene-related peptide (CGRP). The major transmitter involved in the small-diameter pain bers appears to be glutamate. Release of glutamate activates N-methylD-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

NEUROPHYSIOLOGICAL CORRELATES OF CHRONIC PAIN Over the last several decades, a variety of theories have been proposed to explain the neurophysiologic correlates of pain, both acute and chronic. Although there are no universally accepted hypotheses, the gate control theory, proposed by Melzack and Wall (1965) has probably

144 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 bromyalgia, high cervical cordotomy, and other muscular and nonneurologic 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 interfere 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 different aspects of cognitive functioning is unknown, there are a number of possibilities that can be hypothesized. The direct effect of chronic pain-related central neurochemical changes may impact cognition through production of substances that are functionally inhibitory to various aspects of information processing, affecting attention and memory. Secondary effects of chronic pain related to stress and the associated increase in systemic, and more importantly, central glucocorticoid production likely also play a role in impairment of acquisition or consolidation of memories, and secondarily, retrieval (deQuervin, Roozendaal, and McGraugh, 1998). As of yet, there is not a good understanding 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 function 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 central 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) have conceptualized pain as an attention-demanding perceptual stimulus, and attention as a nite and unitary resource. 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 resources. Eccleston and Crombez (1999) further developed

Hart, Martelli, and Zasler a theory dealing with the interruptive function of pain relative to attentional processing. They theorized that pain interruption of attention was mediated through both painrelated characteristics (e.g., the threat value of pain) and environmental demands (e.g., emotional arousal). Pain is therefore selected for action from within complex affective 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 intensity 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 example, 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 performance as a function of the presence or intensity of headache 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 concomitants 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 performance. Kewman et al. (1991) also found that the correlation 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 attentiondemanding task could be accounted for by increased somatic awareness, operationalized as responses to a questionnaire assessing the frequency and breadth of diffuse

Chronic Pain somatic complaints. Increased somatic 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 attention 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 variables 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 persons who seek medical assistance for headache pain and nonpatient volunteers who have similar headache frequency 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 personality 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 between 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 interference with daily activity. The presence of symptoms such as dizziness and visual disturbance of a cervicoencephalic 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 attributed to a disruption in preferred role functions, lifestyles activities, sources of satisfaction and reinforcement, and ones sense of identity and self esteem (Martelli, Zasler, Mancini, and MacMillan, 1999). Cognitive complaints in chronic pain patients are more closely related

145 to measures of emotional distress than to pain variables like rated intensity, and are also associated with interference of everyday activities or at least a reduced desire for activities (Dufton, 1989; Jamison, Sbrocco, and Parris, 1988). Schnurr and MacDonald (1995) found that selfreported cognitive problems and associated mood disturbance 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 cognitive 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 coincided with, or followed, the onset of pain. Rated pain intensity 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, reciprocal relationship appears to exist, wherein pain can contribute to sleep disturbance and depression, sleep disturbance can increase pain symptomatology and mood disturbance, and depression can contribute to sleep disturbance and the affective component of the pain experience. Research to date has not explored in a comprehensive 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 neuropsychological performance or uniquely contribute to subjective complaints or objective signs of impairment in chronic pain populations. Importantly, some of the conditions 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 selection 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, multivariate regression models using independent variables of the type identied in this review would provide valuable information about which factors uniquely inuence neuropsychological functioning in chronic pain patients.

146 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 processing 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 associated 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 intensity. Theoretically, later stages of pain processing would seem likely to mediate effects on cognitive functioning. Sensory-discriminative and affective-motivational components of pain appear to be processed in parallel by different 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 support the proposition that later stages of pain processing play a prominent role in mediating the disruptive inuence of pain on cognition. Examples of identied factors that relate to later stages of pain processing include emotional 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. Preand 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 assessment is beyond the scope of this review, but research

Hart, Martelli, and Zasler ndings have several important implications for the neuropsychological evaluation of patients who have chronic pain as one of their presenting complaints. It is important to recognize that chronic pain and its concomitants represent 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 related symptomatology have not received specic and/or appropriate treatment focus, consideration should be given to postponing neuropsychological assessment until more aggressive medical and behavioral efforts aimed at reducing pain and associated symptoms have been instituted. Especially in situations where adequate pain treatment efforts 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 reduce interference resulting from discomfort and related negative emotion. An especially important consideration is the effect of pain on sleep, as sleep disturbance and resultant daytime fatigue and hypersomnolence may compromise mental efciency. Improved sleep hygiene and pharmacologic and nonpharmacologic treatment of problems with sleep initiation and maintenance may be appropriate prerequisite interventions prior to conducting neuropsychological 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 important role. Symptom checklists that include complaints often associated with chronic pain (e.g., fatigue) are helpful. Sleep surveys may be indicated in specic cases. Efforts 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 seem 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 chronic pain on cognitive performance may be related to increased somatic awareness and emotional factors, standard measures of mood and emotional-personality functioning are important. Caution should be taken to limit potential sensitizing effects or encouragement of symptom focus and over-reporting in patients who are already somatically focused. Identifying emotional suffering, negative illnessrelated beliefs, and lifestyle interference that seem disproportionate to pain intensity should increase the level

Chronic Pain of caution in attributing performance decrements to brain dysfunction from other causes. For this reason, neuropsychological assessment of patients with chronic pain might include pain-specic evaluation techniques such as visual analogue scales to assess pain intensity, concomitant negative 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 such as the Psychosocial Pain Inventory (Gotto and Heaton, 1985), the Multidemensional Pain Inventory (Rudy and Turk, 1987), and the Pain Assessment Battery-Research Edition (Eimer and Allen, 1995). Notably, the latter includes specic subscales for both Extreme Beliefs and Symptom 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 conditioning. 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 reduction procedures as psychoeducation, graduated exposure, and cognitive reinterpretation. In general, accommodations that focus on reducing anxiety can improve performance 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 patient 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 condition, or there is reason to suspect that successful adaptation is likely to depend upon coping with pain-related symptomatology.

147 reviewed here have demonstrated neuropsychological impairment 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 involvement of head and neck areas or a higher incidence of symptoms 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, and fatigue. However, research to date has not explored in a 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 mediate the impact of pain on neuropsychological functioning 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 Neurology, Neurosurgery and Psychiatry 63: 633641. Astrand, N. E. (1987). Medical, psychological, and social factors associated 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 Clinical Journal of Pain 4: 225232. Bell, B. D., Primeau, M., Sweet, J. J., and Loand, K. R. (1999). Neuropsychological 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). Contribution 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 cognitive and behavioral improvement following treatment of disabling orthopaedic complications of a severe closed head injury. Brain Injury 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 memory after common whiplash: A two-years prospective study with age, education and gender pair-matched patients. Acta Neurologica Scandinavia 91: 346352.

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 syndrome and to consider the potential role of pain and associated symptoms in the presentation of patients with documented or presumptive brain injury. Numerous studies

148
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. Psychological Bulletin 125: 356366. Eccleston, C., Crombez, G., Aldrich, S., and Stannard, C. (1997). Attention 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). Neuropsychologic decits and clinical features of post-traumatic temporomandibular 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: A case study illustrating the relationship between pain and neuropsychological test performance. 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 nonpsychotically depressed patients. Neurology 42: 12631267. Kewman, D. G., Vaishampayan, N., Zald, D., and Han, B. (1991). Cognitive 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). Neuropsychological 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 functioning in patients with primary bromyalgia and major depression and healthy controls. Journal of Psychosomatic Research 42: 297 306.

Hart, Martelli, and Zasler

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). Neurobehavioral 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 assessment 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 Rating 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: Recommendations 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 bromyalgia 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: Relationship to neuropsychological performance. Journal of Neuropsychiatry 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 Residency 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 common whiplash. A controlled follow-up study. Archives of Neurology 50: 8791.

Chronic Pain
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). Attentional 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 patients 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 investigation of sympathetic hypersensitivity in chronic fatigue syndrome. Optometry and Visual Science 74: 660663. Sletvold, H., Stiles, T. C., and Landro, N. I. (1995). Information processing in primary bromyalgia, major depression and healthy controls. Journal of Rheumatology 22: 137142. Taylor, A. E., Cox, C. A., and Mailis, A. (1996). Persistent neuropsychological decits following whiplash: Evidence for chronic mild traumatic brain injury? Archives of Physical Medicine and Rehabilitation 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.

149
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 Psychological 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). A canonical correlation analysis of the inuence of neuroticism and 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 maintenance 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 psychological prole of headache-prone individuals. A comparison of clinic patients and controls. Archives of Neurology 52: 602606.