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Review | Clinician's Corner

Prevalence of Chronic Pain After Traumatic Brain Injury:  A Systematic Review FREE

Devi E. Nampiaparampil, MD
[+] Author Affiliations

Author Affiliations: Departments of Internal Medicine and Neurology and Rehabilitation, Veterans Affairs Central California Healthcare System, Fresno.


JAMA. 2008;300(6):711-719. doi:10.1001/jama.300.6.711.
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Published online

Context The Centers for Disease Control and Prevention estimates that approximately 1.4 million US individuals sustain traumatic brain injuries (TBIs) per year. Previous reports suggest an association between TBI and chronic pain syndromes (eg, headache) thought to be more common in patients with mild TBI and in those who have sustained brain injury from violent rather than unintentional trauma. Comorbid psychiatric disorders such as posttraumatic stress disorder (PTSD) may also mediate chronic pain symptoms.

Objectives To determine the prevalence of chronic pain as an underdiagnosed consequence of TBI and to review the interaction between chronic pain and severity of TBI as well as the characteristics of pain after TBI among civilians and combatants.

Evidence Acquisition The Ovid/MEDLINE database was searched for articles published between 1951 and February 2008 using any combination of the terms brain injury, pain, headache, blast injury, and combat (combat disorders, war, military medicine, wounds and injuries, military personnel, veterans). The PubMed and MD Consult databases were searched in a similar fashion. The Cochrane Collaboration, National Institutes of Health Clinical Trials Database, Meta-Register of Current Controlled Trials, and CRISP databases were searched using the keyword brain injury. All articles in peer-reviewed journals reporting original data on pain syndromes in adult patients with TBI with regard to pain prevalence, pain category, risk factors, pathogenesis, and clinical course were selected, and manual searches were performed of their reference lists. The data were pooled and prevalence rates calculated.

Evidence Synthesis Twenty-three studies (15 cross-sectional, 5 prospective, and 3 retrospective) including 4206 patients were identified. Twelve studies assessed headache pain in 1670 patients. Of these, 966 complained of chronic headache, yielding a prevalence of 57.8% (95% confidence interval [CI], 55.5%-60.2%). Among civilians, the prevalence of chronic pain was greater in patients with mild TBI (75.3% [95% CI, 72.7%-77.9%]) compared with moderate or severe TBI (32.1% [95% CI, 29.3%-34.9%]). Twenty studies including 3289 civilian patients with TBI yielded a chronic pain prevalence of 51.5% (95% CI, 49.8%-53.2%). Three studies assessed TBI among 917 veterans and yielded a pain prevalence of 43.1% (95% CI, 39.9%-46.3%). PTSD may mediate chronic pain, but brain injury appears to have an independent correlation with chronic pain.

Conclusions Chronic pain is a common complication of TBI. It is independent of psychologic disorders such as PTSD and depression and is common even among patients with apparently minor injuries to the brain.

Figures in this Article

The Centers for Disease Control and Prevention estimates that approximately 1.4 million US individuals sustain traumatic brain injuries (TBIs) per year.1Quiz Ref IDThe diagnosis can be made subjectively by assessing patients for loss of consciousness (LOC), altered consciousness after a head injury, or posttraumatic amnesia.2 These head injuries can be sustained either when the head forcefully hits an object, when an object penetrates the skull, or when brain tissue undergoes a sudden acceleration, deceleration, or both.

Since 2001, the United States has deployed more than 1.5 million military personnel to Iraq and Afghanistan.3 A higher percentage of these soldiers are now able to survive injuries that would have been fatal in previous wars.4 Among combatants who have returned to the United States, the prevalence of head injuries is estimated at 15.1%.3 Multiple studies have highlighted the importance of brain injuries to US military personnel in Iraq and Afghanistan. Studies of selected military units in Iraq reported that 88% to 97% of their soldiers have sustained blast injuries while in combat5,6 and that 47% to 59% of these soldiers have sustained injuries to the head and neck suggestive of TBI.58 The Defense and Veterans Brain Injury Center estimates that 10% to 20% of all soldiers returning from duty in Iraq and Afghanistan have sustained some type of TBI.9 As of 2008, at least 25 000 soldiers have been diagnosed with TBI, with a projected cost of $14 billion for their care over the next 20 years.9

The association of TBI and chronic pain was described as early as 1915 in troops returning from World War I with “shell shock.”10 Other studies have supported the association between TBI and chronic pain syndromes, the most common of which is headache. One study of Operation Iraqi Freedom/Operation Enduring Freedom veterans experiencing postconcussive syndrome found that posttraumatic stress disorder (PTSD) accounted for all symptoms except pain, suggesting that pain is physiologically linked to brain injury.3

Given the morbidity associated with chronic pain, the strategies available for its early treatment, and the financial burden it imposes on patients and society, this review was undertaken to (1) determine the prevalence of chronic pain syndromes such as headache among patients with TBI; (2) discuss other potential pain syndromes in these patients; (3) describe the relationship between pain and severity of brain injury; (4) investigate the effect of civilian vs combat veteran status on chronic pain after TBI; and (5) examine the role of psychiatric comorbid disorders such as depression, PTSD, and/or substance disorders in posttraumatic pain.

Studies were identified that could provide information on the prevalence of pain among adult patients with TBI. The Ovid/MEDLINE database was searched for articles published between 1951 and February 2008 using any combination of the terms brain injury, pain, headache, blast injury, and combat (combat disorders, war, military medicine, wounds and injuries, military personnel, and veterans). The PubMed and MD Consult databases were searched in a similar fashion for additional articles. The Cochrane Collaboration, National Institutes of Health Clinical Trials Database, Meta-Register of Current Controlled Trials, and CRISP databases were searched using the keyword brain injury.

All selected articles were published in peer-reviewed journals and contained original data on pain syndromes after TBI with respect to prevalence, pain category, risk factors, pathogenesis, and clinical course. Manual searches were performed of the reference lists of selected articles, and the authors of 2 selected studies were contacted for additional citations. The search was not limited by language or publication status. No randomized controlled studies were found in the search (all patients were recruited into studies after the brain injury had occurred). Case reports and review articles were cited only if no other data were available (Figure).

Place holder to copy figure label and caption
Figure. Selection of Articles for Inclusion in Review
Graphic Jump Location

TBI indicates traumatic brain injury.

The initial search yielded 1067 articles, and 43 others were selected from the reference lists of retrieved articles. Of these 1110 articles, 1087 were excluded because they did not fulfill the primary inclusion criteria; ie, the prevalence of chronic pain in their TBI populations could not be calculated. Three studies that met all other criteria were excluded because they focused on individuals younger than 16 years. Two abstracts of unpublished data were also included. The 3 experts contacted for this study were not aware of any negative studies that had not been published.

The data from the final 23 studies were pooled by adding results across studies. Since the studies were cross-sectional (15), prospective observational (5), or retrospective (3), none were given additional weighting. The data from the studies evaluating headache were pooled to determine the overall prevalence of headache among patients with TBI. Subsequently, the studies having groups of patients with mild TBI were compared with the studies having groups of patients with severe TBI to assess respective prevalences of chronic pain. Mild TBI was defined according to American College of Rehabilitation Medicine criteria (Box 1).2 Studies in which the investigators defined the patients as having mild TBI or severe TBI were also included. The studies were then compared with respect to chronic pain between groups of civilians and military survivors.

Box 1. Acute Symptoms of Mild Brain Injury: Definition of Mild Traumatic Brain Injury According to the American Congress of Rehabilitation Medicine2

  1. Any period of loss of consciousness;

  2. Any loss of memory for events immediately before or after the accident;

  3. Any alteration in mental state at the time of the accident (eg, feeling dazed, disoriented, or confused); and

  4. Focal neurological deficit(s) that may or may not be transient; but where the severity of the injury does not exceed the following:

  • Posttraumatic amnesia not greater than 24 h

    After 30 min, an initial Glasgow Coma Scale score of 13-15

    Loss of consciousness of approximately 30 min or less

P values were derived by significance testing of 2 population-proportions using a 2-proportion z test with unequal variances. The results of each individual study were compared with those of the studies combined. The prevalence rates of pain were calculated with 95% confidence intervals (CIs) in each single study and in the pooled data. Analyses were performed using SAS version 9.1 (SAS Institute Inc, Cary, NC); P < .05 was considered statistically significant.

Traumatic brain injury can have detrimental consequences (Box 2).1113Table 11434 and Table 23,35,36 provide a summary of the articles selected for review. Twenty-three studies including 4206 patients reported on the prevalence of chronic pain after TBI.

Box 2. Clinical Characteristics of Traumatic Brain Injury (TBI)

Mild TBI Can Lead to Deficits in

  • Cognition

    Attention

    Memory

    Calculation

    Judgment

    Insight

    Reasoning

  • Sensory processing

    Sight

    Hearing

    Touch

  • Communication

    Language expression

    Understanding

  • Social function

    Compassion

    Interpersonal social awareness

  • Mental health

    Depression

    Anxiety

    Personality changes

    Aggression/irritability

    Social inappropriateness

  • Sleep disturbance

    Vertigo/dizziness

Moderate to Severe TBI Can Have Additional Consequences

  • Abnormal states of consciousness

  • Deficits in speech and swallowing

  • Cranial neuropathies

  • Paresis/paralysis

  • Complications of prolonged bed rest

  • Seizure disorders

  • Movement disorders

All patients can exhibit signs and symptoms of trauma in addition to these symptoms.1113

Table Graphic Jump LocationTable 1. Pain Prevalence in Adult Patients With Traumatic Brain Injury (TBI)a
Table Graphic Jump LocationTable 2. Pain Prevalence In Military Survivors With Traumatic Brain Injury (TBI)a
Headache

Twelve studies14,19,2325,27,2934 reported on headache prevalence after TBI. Of the 1670 patients included in these studies, 966 reported experiencing chronic headache, yielding a prevalence of 57.8% (95% CI, 55.5%-60.2%). Selected studies suggest that headache is a common physical manifestation of TBI14,19,2325,27,2934 and that patients with preexisting headache syndromes often experience worsening of their prior symptoms.23,25

De Benedettis and De Santis19 retrospectively studied 130 consecutive patients with TBI admitted to a university hospital in Milan, Italy. Patients with preexisting headache or who had required neurosurgery were excluded. Pain prevalence was not stratified by injury severity, but descriptive information about TBI severity was provided. After the initial injury, 26% had no change in mental status, 35% had “brief” LOC, 25% were in a superficial coma, 9% were in a coma of intermediate severity, and 5% were in a deep coma. Computed tomography (CT) scans were performed in 65%, with normal results. Sixteen percent of the patients were reevaluated between 6 and 12 months after the injury, 47% were reassessed at 2 years, and 37% had a longer follow-up period that was variable in duration. Posttraumatic headache was reported by 44% of patients after 6 months. Quiz Ref IDPosttraumatic headache began at the time of injury in 30% of patients, between 15 days and 1 month in 21%, between 1 and 3 months in 18%, and after 3 months in 32%. Eleven percent still had headache at 6 months, 54% at 1 year, and 30% after 2 years. The majority of patients (52%) complained of headache of moderate intensity (3-7 on a visual analog scale). Fifty-six percent experienced headache between 4 and 15 times per month. The majority of headaches (51%) occurred in the occipital region. However, among these patients with TBI, no significant relationship was found between the location of the head trauma and the location of pain.

Jensen and Nielsen,23 assessing patients 9 to 12 months after injury, interviewed 168 of 233 patients with suspected cerebral concussion who were admitted over a 1-year period to a county hospital in Denmark. Although 49% of these patients had been hospitalized for a mean duration of 4.3 days, all participants were classified as having sustained mild TBI. Jensen and Nielsen excluded patients with LOC longer than 24 hours, cerebral contusion, or intracerebral hemorrhage. Of the included patients, 29% reported no LOC, 44% had LOC less than 15 minutes, and 39.9% had preexisting headache. After the trauma, 64.3% of patients had headaches, with 34.3% experiencing worsening of their preexisting headache. Four patients (2.4%) reported that their baseline headaches had decreased after the trauma. This is the only selected study that comments on resolution of headache after trauma.

Rimel et al30 studied 538 patients with mild TBI (defined in that study as LOC shorter than 20 minutes, Glasgow Coma Scale [GCS] score of 13 to 15, and hospital length of stay shorter than 48 hours) and conducted interviews with 79%. The 538 patients constituted all of the mild TBIs seen at a university hospital over a 20-month period. Of these patients, 66% were male. Almost half of the patients had been injured in motor vehicle crashes, and 43% had positive blood alcohol levels. Four hundred twenty-four were followed up at 3 months postinjury; of these, 79% had persistent headaches. Of the patients employed at the time of the injury, only 66% remained employed at 3 months.

Uomoto and Esselman33 evaluated 104 patients seen in an outpatient TBI rehabilitation program. Of these, 63.5% were male, 36.5% were female, and the average time postinjury was 26 months. Patients with mild TBI had LOC shorter than 1 hour and GCS scores of 13 to 15, while those with moderate to severe TBI had LOC longer than 1 hour and GCS scores of 12 or less. Of patients with mild TBI, 89% reported headache, compared with 18% of those with severe TBI (P < .001), but similar rates were found for chronic neck/shoulder, back, and other pain symptoms. The group with mild TBI also had a higher frequency of concomitant pain syndromes.

Other Potential Pain Syndromes

Some of the most mystifying pain conditions were first observed during times of war.37 For example, complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy, was first described after the American Civil War. In 1992, Gellman et al21 addressed the issue of CRPS in patients with TBI. In that study, 100 patients admitted consecutively to an inpatient rehabilitation unit with GCS scores less than 8 were evaluated for signs of CRPS. On average, the patients were 4 months post-TBI. During their hospitalizations, 13 patients developed clinical signs and symptoms of CRPS such as pain withdrawal response, vasomotor and temperature changes, discoloration, and palmar fibrosis; these patients underwent formal testing. Of these 13 patients, 12 had bone scan results consistent with CRPS in the upper extremity. These patients also had a combined total of 8 peripheral nerve injuries, 4 fractures, 2 joints with periarticular heterotopic ossification, 1 shoulder dislocation, and 1 rotator cuff tear. Gellman et al found a 12% incidence of CRPS post-TBI, as compared with the 12.5% to 25% incidence of CRPS reported after stroke. 37

Garland et al20 retrospectively reviewed the records of 496 adults with severe TBI admitted to a head trauma service over a 4-year period and, after excluding patients with traumatized joints, found that 100 joints in 57 patients (11%) had painful heterotopic ossification with decreased range of motion in the adjacent joint. Workup for heterotopic ossification was initiated when examiners elicited painful resistance to movement at a joint.

In terms of peripheral neuropathic pain, in a study of 132 inpatients with TBI,18 15 were found to have flaccidity for longer than 1 month, areflexia for longer than 1 month, and abnormal motor patterns. These patients underwent nerve conduction studies and electromyography, and 13 of 132 (10%) were diagnosed with peripheral neuropathies. The mean time elapsed between the trauma and diagnosis was 51 days (range, 14-170). Of the 13 patients, 3 had preventable pressure palsies and 4 had developed signs and symptoms of CRPS.18 This study might not have captured several pain syndromes that can afflict patients. For example, central/deafferentation pain (eg, phantom limb pain) has been cited after TBI.38

Neuromuscular spasticity is often seen in patients with severe TBI. It is theorized to directly cause pain as well as to indirectly lead to painful conditions such as subluxation, tendinitis, and capsulitis.39 However, the presence of pain due to spasticity, as well as the ability of pain to exacerbate preexisting spasticity, has not been well studied,39 and this literature search did not reveal any studies delineating the prevalence of pain in the population of patients with TBI who experience spasticity.

Severity of Brain Injury

Ten studies1416,23,24,27,30,3234 reported the prevalence of pain in patients with mild TBI. Of the 1046 patients included in these studies, 788 reported pain, producing a prevalence rate of 75.3% (95% CI, 72.7%-77.9%). Nine studies1618,2022,24,33,34 furnished data on the prevalence of pain in patients with severe TBI. Of the 1063 patients included in these studies, 341 reported chronic pain, producing a prevalence rate of 32.1% (95% CI, 29.3%-34.9%).

Although this review confirmed the clinical perception that patients with mild TBI have a higher prevalence of chronic pain syndromes than those with moderate to severe TBI (P < .001), it remains unclear why this should be so. Part of the problem may be that patients with more severe TBI may have difficulty reporting or processing their symptoms because of memory disturbances, language deficits, and executive dysfunction.40

Combat Veterans

Given that TBI is the hallmark injury of the current conflicts in Iraq and Afghanistan,9 the high prevalence of chronic pain after TBI is of particular significance. Our literature search produced 3 studies3,35,36 including a total of 917 combat veterans with data regarding the prevalence of pain among patients with combat-associated brain injuries. Of these 917 patients, 395 complained of pain, yielding an estimated prevalence rate of 43.1% (95% CI, 39.9%-46.3%). These 3 studies3,35,36 described 329 of the 917 combat veterans as having headache, producing a prevalence rate of 35.9% (95% CI, 32.8%-39.0%). Twenty studies1434 including a total of 3289 civilian patients with TBI yielded a chronic pain prevalence of 51.5%.

Hoge et al3 performed a large cross-sectional study of 2525 US Army Infantry soldiers with combat exposure in Iraq or Afghanistan. Of these, 95.5% were men and 55.5% were younger than 30 years. Of those soldiers who had attended study recruitment meetings, 59% completed the study. The lack of availability for soldiers to complete the questionnaires was attributed to normal transfers and training, although it is possible that soldiers with more serious illnesses and injuries did not have the opportunity to participate. Although the study used a convenience sample, it appears to be representative of Operation Iraqi Freedom/Operation Enduring Freedom veterans. The soldiers were questioned at 3 to 4 months after their return to the United States to provide an appropriate amount of time to assess for postconcussive symptoms while minimizing recall bias. Of the soldiers completing the study, 4.9% experienced LOC shorter than 30 minutes, and 10.3% had alterations in mental status without LOC. Criteria for PTSD were met by 43.9% of soldiers with LOC and 27.3% of those with altered mental status without LOC; PTSD also was diagnosed in 16.2% of the soldiers with injuries other than TBI and in 9.1% of uninjured soldiers. Quiz Ref IDControlling for other factors, LOC and combat intensity remained significantly associated with PTSD (odds ratio for LOC, 2.98 [95% CI, 1.70-5.24]; for highest vs lowest quartiles of combat intensity, 11.58 [95% CI, 2.99-44.82]), and LOC was independently associated with the diagnosis of major depression (odds ratio, 3.67 [95% CI, 1.65-8.16]). After adjusting for PTSD and depression, TBI was no longer correlated with any physical health symptoms except for headache pain.

Walker et al35 evaluated 109 patients with severe TBI seen consecutively at 1 of 4 rehabilitation Veterans Affairs medical centers. These patients were seen for acute rehabilitation and reevaluated at 6 and 12 months. Of the 109 patients, 38% had acute postconcussive headache, with 48.8% experiencing this in the frontal area; 75.6% had daily headache. No relationship was found between the presence of headache and demographic, injury severity, or emotional variables. Improvement at 6 months was associated with less anxiety and depression. Of the patients who had headache at 6 months, 95.5% continued to have headache at 12 months. At the times of follow-up, the severity of posttraumatic headache had decreased.

Contrary to expectations, the prevalence rate of pain after TBI appears to be higher in civilians than in combat veterans. This could be due to a variety of reasons. Military survivors may be less likely to report pain because of factors such as peer pressure or fear of being medically evaluated and perhaps separated from fellow soldiers. Conversely, civilians may be more likely to overreport their pain, potentially for secondary gain. Or, since convenience samples were used, civilians with unresolved pain may be recruited more frequently into these studies. The characteristics of the samples may differ as well.

Military personnel may be healthier than their civilian cohorts. Previous studies have suggested that pain in soldiers is primarily due to the increased level of physical activity experienced during military training.41

Of the 3 studies of combat veterans,3,35,36 2 were performed immediately after the soldiers returned from deployment.35,36 It could be argued that this was too early for chronic posttraumatic headache to develop. However, in a retrospective study of 70 civilian outpatients experiencing posttraumatic headache, 35% developed the headache within an hour of the initial trauma, 14% within 24 hours, and 27% within 7 days. Of the 70 outpatients, 56% described chronic daily headache with symptoms for at least 21 of the 30 days recorded. Most patients reported that the pain was of at least moderate intensity and often interfered with work-related and other functional activities.42

Finally, given the importance that the Departments of Defense and Veterans' Affairs have placed on TBI screening among returning soldiers as well as the overlap in criteria between TBI and PTSD among other psychiatric disorders, the number of true TBIs in the military sample may be overestimated. This in turn may dilute the sample and cause an underestimation of the true prevalence of pain in that population.

Military survivors with brain injuries may have a variety of pain syndromes. In the survey by Hoge et al,3 in those soldiers who reported having sustained TBI during deployment (as compared with soldiers having other injuries), 32.2% had headache (P < .001), 14.0% had chest pain (P < .001), and 8.3% had pain or problems during sexual intercourse (P = .04). Although the difference between groups was not statistically significant, individuals with TBI also reported stomach pain (11.7%), back pain (33.1%), and arm, leg, or joint pain (37.2%).

It is possible that individuals having TBI due to violent trauma, such as assaults, have increased pain compared with those having TBI due to unintentional trauma, such as sports injuries or falls.43 This review could not distinguish civilians who had sustained TBI through random violence from the rest of the sample. Although patients who had sustained violent injuries were not excluded from any of the studies reviewed, none of the studies created subgroups based on mechanism of injury.

Psychiatric Disorders

The relationship between pain and mood disorders such as depression is complex. Hoffman et al22 evaluated 146 of 202 consecutive patients during inpatient rehabilitation and at 1 year postinjury. These patients had severe TBI, defined as a GCS score of 12 or less. Of the 146 patients, 76% were male and 24% were female; 78.1% were white and 21.9% were of other race/ethnicity; and 48.6% were injured in motor vehicle crashes and 11.6% through violence. Of the evaluated patients, 72.6% had pain 1 year out from their injuries, and 55% reported interference with activities of daily living. The mean bodily pain score on the 36-Item Short-Form Health Survey was 66.7 on a scale of 100. Higher pain scores at 1 year postinjury were associated with depression during inpatient rehabilitation, female sex, and race/ethnicity other than white. Pain was associated with community participation, but, when depression was factored in, the pain variable lost significance. This study underscores the relationship between pain and mood disorders.

Bryant et al17 examined 96 of 161 patients admitted for severe TBI to a tertiary-care TBI unit to determine whether there was a relationship between pain and PTSD measures. In that study, 22 patients were excluded because of cognitive dysfunction causing them to be unable to understand or respond to the interviewer. The final population was evaluated between 5 and 7 months posttrauma. Chronic pain was defined as pain at least once a week of greater than 6 months' duration. The McGill Pain Questionnaire and a 10-point scale were used to assess pain complaints. Of the included patients, 62% reported chronic pain, 24% reported daily pain, and 7% reported constant pain. Bryant et al found that higher pain severity was associated with increased severity of PTSD, depression, poor satisfaction with life, and avoidant coping style. After controlling for the effects of PTSD, the only factor that still correlated with pain severity was avoidant coping style.

Other studies have supported the relationship between chronic pain syndromes and PTSD.4447 Trauma patients with multiple symptoms of PTSD generally report higher levels of pain and affective disturbances than those who do not have many symptoms of PTSD.48

The relationship between brain injury and PTSD has been debated since 1939, when Schaller31 surmised that the rate of pain in posttrauma psychoneurotic states would be greater than that in patients with TBI. In the cohort of 100 patients with TBI in that study, 77% had persistent headache, which was similar to the rate of headache (97%) in patients with “posttraumatic psychoneurosis or hysteria.”

Quiz Ref IDPTSD may be associated with increased pain severity for many reasons. Pain perception can be heightened by increased anxiety, and the ability to cope with pain in PTSD may be impeded by catastrophic interpretations of pain. In addition, patients may not have the concentration required, due to intrusive thoughts, to use cognitive strategies to reduce pain. Alternatively, they may display an attentional bias to negative events. Finally, the concordance between PTSD and somatoform pain disorder is high.17

Although several studies attest that substance abuse may be a causative factor in the occurrence,49 severity,50 and prognosis50 of TBI, no studies have examined the relationship between substance abuse and pain after TBI. It is possible, however, that patients may use illicit substances to self-medicate for pain.

This review is limited by several factors. First, all of the studies were cross-sectional, observational, or retrospective. Second, the civilian study populations demonstrated heterogeneity in terms of comorbid psychiatric disorders, cause of injury, and time elapsed since injury, as well as in the recruitment procedures. Patients were recruited from rehabilitation units and clinics but not from skilled nursing facilities, where the most severely injured patients might reside. All of the studies used convenience samples rather than random samples. Quiz Ref IDThird, all of the information gathered relied on patient report. It is possible that patients with TBI who had more cognitive dysfunction were unable to comprehend or accurately respond to questions about their pain. Fourth, the definition of TBI varied across studies, as did the definitions and measures of chronic pain. Fifth, most studies did not provide information key to subgroup analyses.

Further research in brain injury would benefit from standardized criteria for measurement of severity of TBI. Data analysis would be enhanced by reporting of symptoms based on severity, mechanism, and duration of injury, as well as on comorbid psychiatric disorders.

Chronic pain is a common complication of TBI and contributes to morbidity and potentially poor recovery after brain injury. Patients who appear clinically to have less severe brain injuries may in fact develop more pain symptoms. Patients who have sustained TBIs in combat have a higher rate of chronic pain than the general population. However, they appear to have lower rates of pain than civilians with TBI. Patients with TBI would benefit from early screening and treatment for pain syndromes to decrease the morbidity that untreated chronic pain additionally imposes on them and on society. In addition, clinicians treating patients who have any history of mild head injuries should consider inquiring further about coexisting symptoms. These may affect how the patients comprehend and follow treatment recommendations.

Corresponding Author: Devi E. Nampiaparampil, MD, Department of Neurology and Rehabilitation, Veterans Affairs Central California Healthcare System, 2615 E Clinton Ave, Fresno, CA 93703 (devichechi@gmail.com).

Author Contributions: Dr Nampiaparampil had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosures: Dr Nampiaparampil reported previously serving on a research advisory board for Elan Pharmaceuticals.

Additional Contributions: I thank Daphne Perry (VA Central California Healthcare System) for expeditiously acquiring the articles reviewed in this meta-analysis, Robert Nampiaparampil, MD (Northwestern University Feinberg School of Medicine), for his indispensable statistical and technical contributions, and John Pang, MD (Division of Cardiology, Northwestern Memorial Hospital), for his insightful comments and invaluable editorial recommendations. None of these individuals received compensation for their contributions.

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Gellman H, Keenan ME, Stone L,  et al.  Reflex sympathetic dystrophy in brain-injured patients.  Pain. 1992;51(3):307-311
PubMed   |  Link to Article
Hoffman JM, Pagulayan KF, Zawaideh N,  et al.  Understanding pain after TBI: impact on community participation.  Am J Phys Med Rehabil. 2007;86(12):962-969
PubMed   |  Link to Article
Jensen OK, Nielsen FF. The influence of sex and pre-traumatic HA on the incidence and severity of HA after head injury.  Cephalalgia. 1990;10(6):285-293
PubMed   |  Link to Article
Lahz S, Bryant RA. Incidence of chronic pain following TBI.  Arch Phys Med Rehabil. 1996;77(9):889-891
PubMed   |  Link to Article
Landy PJ. Neurological sequelae of minor head and neck injuries.  Injury. 1998;29(3):199-206
PubMed   |  Link to Article
Leung J, Moseley A, Fereday S,  et al.  The prevalence and characteristics of shoulder pain after TBI.  Clin Rehabil. 2007;21(2):171-191
PubMed   |  Link to Article
Mooney G, Speed J, Sheppard S. Factors related to recovery after mTBI.  Brain Inj. 2005;19(12):975-987
PubMed   |  Link to Article
Olver JH, Ponsford JL, Curran CA. Outcome following TBI: a comparison between 2 and 5 years after injury.  Brain Inj. 1996;10(11):841-848
PubMed   |  Link to Article
Ouellet MC, Beaulieu-Bonneau S, Morin CM. Insomnia in patients with TBI: frequency, characteristics, and risk factors.  J Head Trauma Rehabil. 2006;21(3):199-212
PubMed   |  Link to Article
Rimel RW, Giordani B, Barth JT,  et al.  Disability caused by minor head injury.  Neurosurgery. 1981;9(3):221-228
PubMed   |  Link to Article
Schaller WF. After-effects of head injury.  J Am Med Assoc. 1939;113(20):1779-1785
Link to Article
Smith-Seemiller L, Fow NR, Kant R,  et al.  Presence of post-concussion syndrome symptoms in patients with chronic pain vs. mTBI.  Brain Inj. 2003;17(3):199-206
PubMed   |  Link to Article
Uomoto JM, Esselman PC. TBI and chronic pain: differential types and rates by head injury severity.  Arch Phys Med Rehabil. 1993;74(1):61-64
PubMed
Yamaguchi M. Incidence of headache and severity of head injury.  Headache. 1992;32(9):427-431
PubMed   |  Link to Article
Walker WC, Seel RT, Curtiss G, Warden DL. HA after moderate and severe TBI: a longitudinal analysis.  Arch Phys Med Rehabil. 2005;86(9):1793-1800
PubMed   |  Link to Article
Warden DL, Ryan LM, Helmick KM,  et al.  War Neurotrauma: the Defense and Veterans Brain Injury Center (DVBIC) Experience at Walter Reed Army Medical Center. Washington, DC: Walter Reed Army Medical Center; 2005:60
Office of Communications and Public Liaison, National Institute of Neurological Disorders and Stroke, National Institutes of Health.  Complex Regional Pain Syndrome Fact Sheet 2003Bethesda, MD: National Institutes of Health; 2003. NIH publication 04-4173
Andersen G, Vestergaard K, Ingeman-Nielsen M, Jensen TS. Incidence of central post-stroke pain.  Pain. 1995;61(2):187-194
PubMed   |  Link to Article
Zafonte R, Elovic EP, Lombard L. Acute care management of post-TBI spasticity.  J Head Trauma Rehabil. 2004;19(2):89-100
PubMed   |  Link to Article
Sherman KB, Goldberg M, Bell KR. TBI and pain.  Phys Med Rehabil Clin N Am. 2006;17(2):473-490
PubMed   |  Link to Article
Shaffer RA, Brodine SK, Ito SI, Le AT. Epidemiology of illness and injury among U.S. Navy and Marine Corps female training populations.  Mil Med. 1999;164(1):17-21
PubMed
Fioravanti M, Ramelli L, Napoleoni A,  et al.  Post-traumatic headache: neuropsychological and clinical aspects.  Cephalalgia. 1983;3(1):(suppl 1)  221-224
PubMed
Kirschblum S, Campagnolo D, De Lisa JA. Spinal Cord Injury Medicine. Philadelphia, PA: Lippincott Williams & Wilkins; 2001
Meltzer-Brody S, Leserman J, Zolnoun D, Steege J, Green E, Teich A. Trauma and posttraumatic stress disorder in women with chronic pelvic pain.  Obstet Gynecol. 2007;109(4):902-908
PubMed   |  Link to Article
Asmundson GJ, Wright KD, Stein MB. Pain and PTSD symptoms in female veterans.  Eur J Pain. 2004;8(4):345-350
PubMed   |  Link to Article
Geuze E, Westenberg HG, Jochims A,  et al.  Altered pain processing in veterans with posttraumatic stress disorder.  Arch Gen Psychiatry. 2007;64(1):76-85
PubMed   |  Link to Article
Whalley MG, Farmer E, Brewin CR. Pain flashbacks following the July 7th 2005 London bombings.  Pain. 2007;132(3):332-336
PubMed   |  Link to Article
Geisser ME, Roth RS, Bachman JE, Eckert TA. The relationship between symptoms of post-traumatic stress disorder and pain, affective disturbance, and disability among patients with accident and non-accident related pain.  Pain. 1996;66(2-3):207-214
PubMed   |  Link to Article
Bombardier CH, Rimmele CT, Zintel H. The magnitude and correlates of alcohol and drug use before traumatic brain injury.  Arch Phys Med Rehabil. 2002;83(12):1765-1773
PubMed   |  Link to Article
Bogner JA, Corrigan JD, Mysiw WJ, Clinchot D, Fugate L. A comparison of substance abuse and violence in the prediction of long-term rehabilitation outcomes after traumatic brain injury.  Arch Phys Med Rehabil. 2001;82(5):571-577
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure. Selection of Articles for Inclusion in Review
Graphic Jump Location

TBI indicates traumatic brain injury.

Tables

Table Graphic Jump LocationTable 1. Pain Prevalence in Adult Patients With Traumatic Brain Injury (TBI)a
Table Graphic Jump LocationTable 2. Pain Prevalence In Military Survivors With Traumatic Brain Injury (TBI)a

References

Langlois JA, Rutland-Brown W, Thomas KE. Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations, and Deaths. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2004
Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine.  The definition of traumatic brain injury.  J Head Trauma Rehabil. 1993;8(3):86-87
Link to Article
Hoge CW, McGurk D, Thomas JL,  et al.  Mild traumatic brain injury in U.S. soldiers returning from Iraq.  N Engl J Med. 2008;358(5):453-463
PubMed   |  Link to Article
Tanelian T, Jaycox L. Invisible Wounds of War: Psychological and Cognitive Injuries, Their Consequences, and Services to Assist Recovery. Santa Monica, CA: Rand Monographs; 2008
Murray CK, Reynolds JC, Schroeder JM,  et al.  Spectrum of care provided at an echelon II medical unit during Operation Iraqi Freedom.  Mil Med. 2005;170(6):516-520
PubMed
Gondusky JS, Reiter MP. Protecting military convoys in Iraq: an examination of battle injuries sustained by a mechanized battalion during Operation Iraqi Freedom II.  Mil Med. 2005;170(6):546-549
PubMed
Warden DL, Ryan LM, Helmick KM,  et al.  War neurotrauma: the Defense and Veterans Brain Injury Center (DVBIC) experience at Walter Reed Army Medical Center (WRAMC) [abstract].  J Neurotrauma. 2005;22:1178
Cernak I, Savic J, Ignjatovic D,  et al.  Blast injury from explosive munitions.  J Trauma. 1999;47(1):96-103
PubMed   |  Link to Article
Bhattacharjee Y. Shell shock revisited: solving the puzzle of blast trauma.  Science. 2008;319(5862):406-408
PubMed   |  Link to Article
Myers CS. A contribution to the study of shellshock: being an account of the cases of loss of memory, vision, smell and taste admitted to the Duchess of Westminster's War Hospital, Le Touquet.  Lancet. 1915;1:316-320
Link to Article
Office of Communications and Public Liaison, National Institute of Neurological Disorders and Stroke, National Institutes of Health.  Traumatic Brain Injury: Hope Through ResearchBethesda, MD: National Institutes of Health; 2002. NIH publication 02-2478
 Facts about concussion and brain injury. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/ncipc/tbi/default.htm. 1999. Accessibility verified June 27, 2008
Warden DL, Gordon B, McAllister TW,  et al; Neurobehavioral Guidelines Working Group.  Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury.  J Neurotrauma. 2006;23(10):1468-1501
PubMed   |  Link to Article
Alfano DP, Asmundson GJG, Larsen DK,  et al.  MTBI and chronic pain: preliminary findings [abstract].  Arch Clin Neuropsychol. 2000;15:831-832
Alfano DP. Emotional and pain-related factors in neuropsychological assessment following mTBI.  Brain Cogn. 2006;60(2):193-217
PubMed   |  Link to Article
Beetar JT, Guilmette TJ, Sparadeo FR. Sleep and pain complaints in symptomatic TBI and neurologic populations.  Arch Phys Med Rehabil. 1996;77(12):1298-1302
PubMed   |  Link to Article
Bryant RA, Marosszeky JE, Crooks J,  et al.  Interaction of posttraumatic stress disorder and chronic pain following TBI.  J Head Trauma Rehabil. 1999;14(6):588-594
PubMed   |  Link to Article
Cosgrove JL, Vargo M, Reidy ME. A prospective study of peripheral nerve lesions occurring in traumatic brain-injured patients.  Am J Phys Med Rehabil. 1989;68(1):15-17
PubMed   |  Link to Article
De Benedittis G, De Santis A. Chronic post-traumatic HA: clinical, psychopathological features and outcome determinants.  J Neurosurg Sci. 1983;27(3):177-186
PubMed
Garland DE, Blum CE, Waters RL. Periarticular heterotopic ossification in head-injured adults: incidence and location.  J Bone Joint Surg Am. 1980;62(7):1143-1146
PubMed
Gellman H, Keenan ME, Stone L,  et al.  Reflex sympathetic dystrophy in brain-injured patients.  Pain. 1992;51(3):307-311
PubMed   |  Link to Article
Hoffman JM, Pagulayan KF, Zawaideh N,  et al.  Understanding pain after TBI: impact on community participation.  Am J Phys Med Rehabil. 2007;86(12):962-969
PubMed   |  Link to Article
Jensen OK, Nielsen FF. The influence of sex and pre-traumatic HA on the incidence and severity of HA after head injury.  Cephalalgia. 1990;10(6):285-293
PubMed   |  Link to Article
Lahz S, Bryant RA. Incidence of chronic pain following TBI.  Arch Phys Med Rehabil. 1996;77(9):889-891
PubMed   |  Link to Article
Landy PJ. Neurological sequelae of minor head and neck injuries.  Injury. 1998;29(3):199-206
PubMed   |  Link to Article
Leung J, Moseley A, Fereday S,  et al.  The prevalence and characteristics of shoulder pain after TBI.  Clin Rehabil. 2007;21(2):171-191
PubMed   |  Link to Article
Mooney G, Speed J, Sheppard S. Factors related to recovery after mTBI.  Brain Inj. 2005;19(12):975-987
PubMed   |  Link to Article
Olver JH, Ponsford JL, Curran CA. Outcome following TBI: a comparison between 2 and 5 years after injury.  Brain Inj. 1996;10(11):841-848
PubMed   |  Link to Article
Ouellet MC, Beaulieu-Bonneau S, Morin CM. Insomnia in patients with TBI: frequency, characteristics, and risk factors.  J Head Trauma Rehabil. 2006;21(3):199-212
PubMed   |  Link to Article
Rimel RW, Giordani B, Barth JT,  et al.  Disability caused by minor head injury.  Neurosurgery. 1981;9(3):221-228
PubMed   |  Link to Article
Schaller WF. After-effects of head injury.  J Am Med Assoc. 1939;113(20):1779-1785
Link to Article
Smith-Seemiller L, Fow NR, Kant R,  et al.  Presence of post-concussion syndrome symptoms in patients with chronic pain vs. mTBI.  Brain Inj. 2003;17(3):199-206
PubMed   |  Link to Article
Uomoto JM, Esselman PC. TBI and chronic pain: differential types and rates by head injury severity.  Arch Phys Med Rehabil. 1993;74(1):61-64
PubMed
Yamaguchi M. Incidence of headache and severity of head injury.  Headache. 1992;32(9):427-431
PubMed   |  Link to Article
Walker WC, Seel RT, Curtiss G, Warden DL. HA after moderate and severe TBI: a longitudinal analysis.  Arch Phys Med Rehabil. 2005;86(9):1793-1800
PubMed   |  Link to Article
Warden DL, Ryan LM, Helmick KM,  et al.  War Neurotrauma: the Defense and Veterans Brain Injury Center (DVBIC) Experience at Walter Reed Army Medical Center. Washington, DC: Walter Reed Army Medical Center; 2005:60
Office of Communications and Public Liaison, National Institute of Neurological Disorders and Stroke, National Institutes of Health.  Complex Regional Pain Syndrome Fact Sheet 2003Bethesda, MD: National Institutes of Health; 2003. NIH publication 04-4173
Andersen G, Vestergaard K, Ingeman-Nielsen M, Jensen TS. Incidence of central post-stroke pain.  Pain. 1995;61(2):187-194
PubMed   |  Link to Article
Zafonte R, Elovic EP, Lombard L. Acute care management of post-TBI spasticity.  J Head Trauma Rehabil. 2004;19(2):89-100
PubMed   |  Link to Article
Sherman KB, Goldberg M, Bell KR. TBI and pain.  Phys Med Rehabil Clin N Am. 2006;17(2):473-490
PubMed   |  Link to Article
Shaffer RA, Brodine SK, Ito SI, Le AT. Epidemiology of illness and injury among U.S. Navy and Marine Corps female training populations.  Mil Med. 1999;164(1):17-21
PubMed
Fioravanti M, Ramelli L, Napoleoni A,  et al.  Post-traumatic headache: neuropsychological and clinical aspects.  Cephalalgia. 1983;3(1):(suppl 1)  221-224
PubMed
Kirschblum S, Campagnolo D, De Lisa JA. Spinal Cord Injury Medicine. Philadelphia, PA: Lippincott Williams & Wilkins; 2001
Meltzer-Brody S, Leserman J, Zolnoun D, Steege J, Green E, Teich A. Trauma and posttraumatic stress disorder in women with chronic pelvic pain.  Obstet Gynecol. 2007;109(4):902-908
PubMed   |  Link to Article
Asmundson GJ, Wright KD, Stein MB. Pain and PTSD symptoms in female veterans.  Eur J Pain. 2004;8(4):345-350
PubMed   |  Link to Article
Geuze E, Westenberg HG, Jochims A,  et al.  Altered pain processing in veterans with posttraumatic stress disorder.  Arch Gen Psychiatry. 2007;64(1):76-85
PubMed   |  Link to Article
Whalley MG, Farmer E, Brewin CR. Pain flashbacks following the July 7th 2005 London bombings.  Pain. 2007;132(3):332-336
PubMed   |  Link to Article
Geisser ME, Roth RS, Bachman JE, Eckert TA. The relationship between symptoms of post-traumatic stress disorder and pain, affective disturbance, and disability among patients with accident and non-accident related pain.  Pain. 1996;66(2-3):207-214
PubMed   |  Link to Article
Bombardier CH, Rimmele CT, Zintel H. The magnitude and correlates of alcohol and drug use before traumatic brain injury.  Arch Phys Med Rehabil. 2002;83(12):1765-1773
PubMed   |  Link to Article
Bogner JA, Corrigan JD, Mysiw WJ, Clinchot D, Fugate L. A comparison of substance abuse and violence in the prediction of long-term rehabilitation outcomes after traumatic brain injury.  Arch Phys Med Rehabil. 2001;82(5):571-577
PubMed   |  Link to Article
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